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  • 1
    Electronic Resource
    Electronic Resource
    Effects of Experimental Chemoendocrine Therapy With a Combination of a Pure Antiestrogen and 5-Fluorouracil on Human Breast Cancer Cells Implanted in Nude Mice (1999)
    Springer
    Surgery today 29 (1999), S. 149-156 
    Details
    ISSN: 1436-2813
    Keywords: Key Words: chemoendocrine therapy ; pure antiestrogen ; 5-fluorouracil ; nude mouse ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s005950050376
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  • 2
    Electronic Resource
    Electronic Resource
    Bestandsverminderung bei verwilderten Haustauben Teil 1 Bilanz mitteleuropäischer Stadtverwaltungen (1999)
    Springer
    Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz 42 (1999), S. 911-921 
    Details
    ISSN: 1437-1588
    Keywords: Schlüsselwörter ; Verwilderte Haustauben (Columba livia domestica) ; Bestandsregulierung ; Stadthygiene ; Gesundheitsschutz ; Ökologisches Management ; Key words ; Feral pigeons ; Street pigeons (Columba livia domestica) ; Population reduction ; Habitat manipulation ; Urban hygiene ; Public health ; Bird management strategies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The report, in two parts, sums up the findings of a survey covering 52 cities in Central Europe. Most administrations have imposed a ban on feeding street pigeons, but this has been more or less unsuccessful. Information campaigns were used on a large scale, along with more controversial methods such as catching the birds or shooting them down, providing pigeon houses, administering hormone preparations, chemosterilization, and exclusion from buildings. Few attempts were made to reduce the number of breeding places. Population reduction by poisons or natural enemies seems to be negligible. The findings of the survey are compared with results reported in the specialist literature, followed by a discussion of the ecological, hygienic and legal aspects, including animal protection, pest control, and public health. The strategy proposed to improve the present situation, which is found unsatisfactory in many respects, is to organize along the principles of ecological management. By optimizing the available options and following scientific criteria, it aims to combine those methods which appear most promising under local conditions. Any drawbacks are to be compensated by the enhancement of positive elements to give the best possible overall results.
    Notes: Zusammenfassung Der zweiteilige Bericht faßt die Ergebnisse einer Umfrage zusammen, bei der sich die Verwaltungen von 52 mitteleuropäischen Städten zum Straßentaubenproblem geäußert haben. Überwiegend versucht man mehr oder minder erfolglos, eine Bestandsverminderung durch Taubenfütterungsverbot zu erreichen. Häufig wird auch von Bürgerbelehrungen und Informationskampagnen berichtet. Ferner spielen Fangaktionen, Taubenhäuser, Hormonpräparate und Chemosterilantien, Abschuß und Absperrmaßnahmen an Gebäuden eine meist ambivalente Rolle. Bei der Verminderung der Brutplatzangebote sind nur schwache Bemühungen erkennbar. Natürliche Feinde (Greifvögel) scheinen in den wenigsten Städten eine Rolle bei der Reduzierung von Straßentauben zu spielen. Vergiftungen werden offenbar nicht mehr vorgenommen. Die Erfahrungen der Kommunen werden mit den in der Fachliteratur vorliegenden Ergebnissen verglichen. Kommentare aus ökologischer und hygienezoologischer Sicht berücksichtigen die rechtlichen Grundlagen von Tierschutz, Schädlingsbekämpfung und Gesundheitsvorsorge. Um die insgesamt noch sehr unbefriedigende Situation bei der Bestandsverminderung von verwilderten Haustauben zu verbessern, wird ein Strategieprogramm nach den Organisationsprinzipien des „ökologischen Managements” vorgeschlagen. Hierzu sollten sämtliche anwendbaren Möglichkeiten nach wissenschaftlichen Kriterien optimiert und den jeweils stadtspezifischen Umständen entsprechend so miteinander kombiniert werden, daß methodische Nachteile durch die Vorteile anderer Komponenten ausgeglichen werden und das Gesamtkonzept nach dem Verstärkerprinzip Optimalergebnisse erzielt.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001030050221
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  • 3
    Electronic Resource
    Electronic Resource
    Das Frankfurter Bleiprojekt Maßnahmen zur Einhaltung des Grenzwertes für Blei im Trinkwasser (1999)
    Springer
    Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz 42 (1999), S. 902-910 
    Details
    ISSN: 1437-1588
    Keywords: Schlüsselwörter ; Trinkwasser ; Bleileitungen ; Key words ; Drinking water ; Lead pipes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary On 3.11.1998 the Drinking Water Directive passed the European Parliament. This new directive will lower the current limit value for lead in Germany from 0,040 mg/l to 0,025 mg/l in 2003 and to 0,010 mg/l in 2013. Since there are still around 7800 premises with plumbing-systems containing lead-pipes in Frankfurt, the Stadtgesundheitsamt started the „Frankfurt Lead-Project” in 1997. Aim of the project was the investigation and, if necessary, the order to exchange all concerned plumbing systems. The owners of the buildings are liable to a fee for these measures of the local public health service, thus covering of the costs should be attainable. Within the project 3 to 5 water probes from each concerned building were sampled, to take the stagnation-problem into account. The drinking water of 50% of the investigated flats reached the EG-parametric value of 0,01 mg/l, which has to be transferred into national law from 2013 on the latest. Houses with plumbing-systems not containing lead were part of this sample. A sample of houses with only lead containing plumbing systems would result in considerably higher values. The mean lead-concentration after a stagnation-period of 3 hours was 0,034 mg/l and therefore significantly exceeded the EG-parametric value of 0,025 mg/l. Experts agree that the future EG-parametric values can not be met with special water treatments, but only by replacement of lead pipes by pipes composed of other suitable materials. Even pipe-coating techniques can not be recommended at this time. To our experience the new EG-parametric-value for lead of 0,025 mg/l, which has to be transferred into national law by the european member states from 2003 on, will require the sanitation of nearly every house with a lead-containing plumbing system. All the more so because the EG-parametric-value of 0,10 mg/l will become effective from 2013 on, what factually equals a prohibition of lead-pipes. Considering the time given by the EG-Drinking Water Guideline and the experience reported here we conclude that compliance with the new EG-parametric values would not be possible for most of the German cities and communities having a lead-pipe problem. It is foreseeable therefore, that the Federal Republic of Germany will have to face complaints for non-compliance with the parametric value from the European Commission. Based on the experiences with the lead-project we would recommend the prohibition of lead pipes whithin domestic distribution systems as an appropriate measure to achieve compliance with the parametric value for lead. Such a prohibition would make it possible to meet the parametric value for lead, create a reliable legal situation for both consumers and owners of the concerned plumbing systems, save considerable expenses for staff and laboratory tests, make the exchange of lead-containing installations easy to plan and would avoid conflicts about the interpretation of monitoring results.
    Notes: Zusammenfassung Durch die am 3.11.1998 vom Europäischen Parlament verabschiedete Richtlinie des Rates der Europäischen Gemeinschaft über die Qualität von Wasser für den menschlichen Gebrauch muß eine Absenkung des Bleigrenzwertes in Deutschland von derzeit 0,040 mg/l auf 0,025 mg/l bis spätestens zum Jahr 2003 und auf 0,010 mg/l bis spätestens zum Jahr 2013 erfolgen. Da in Frankfurt a.M. bekannt war, daß noch ca. 7800 Liegenschaften mit bleihaltigen Hausinstallationen ausgestattet sind, wurde ab 1997 im Stadtgesundheitsamt das „Blei-Projekt” gestartet, mit dem eine Untersuchung und ggf. erforderliche Sanierung aller betreffenden Häuser binnen max. zehn Jahren ab 1996 unter dem Aspekt der Kostendeckung durchgesetzt werden soll. Pro untersuchtem Haus wurden mehrere Proben entnommen, um das Stagnationsproblem adäquat zu berücksichtigen. In 50% der von uns untersuchten Wohnungen, unter denen sich auch Hausinstallationen ohne Bleileitungen befanden, wurde der ab dem Jahr 2013 geltende Grenzwert von 0,010 mg/l bereits erreicht. Bei einer nur aus bleihaltigen Hausinstallationen bestehenden Stichprobe ist aufgrund unserer Daten zu erwarten, daß dieser Wert sogar deutlich überschritten würde. Der Mittelwert der Leitungsproben nach 3 Stunden Stagnation überschreitet mit 0,034 mg/l den ab dem Jahr 2003 geltenden Grenzwert von 0,025 mg/l klar. Aus der Fachdiskussion ist bekannt, daß sich die zukünftigen Grenzwerte nicht mit Aufbereitungsmaßnahmen wie Phosphatierung u.ä. einhalten lassen werden, sondern daß der Austausch der Bleileitungen gegen Leitungen aus geeigneten Werkstoffen der einzig in Frage kommende Sanierungsweg ist. Auch mit Innenbeschichtungen arbeitende Sanierungstechniken können derzeit nicht empfohlen werden. Schon die Festsetzung des Trinkwasser-Grenzwertes für Blei von zunächst 0,025 mg/l ab dem Jahr 2003 bedeutet daher, daß nahezu jede bleihaltige Hausinstallation bis dahin durch vollständiges Austauschen der Bleirohre saniert werden muß. In jedem Fall gilt dies für die Einführung des Parameterwertes von 0,010 mg/l ab dem Jahr 2013, was faktischen einem Verbot von Bleileitungen gleichkommt. Aus den gegebenen Fristen und den hier gemachten Erfahrungen hinsichtlich der benötigten Bearbeitungszeiten ist die Erkenntnis abzuleiten, daß ein Vollzug der Trinkwasserverordnung ohne ein möglichst auf klare europaweite Rechtsvorschriften gegründetes Verbot in den meisten betroffenen Bundesländern, Kreisen und kreisfreien Städten nicht möglich sein wird und somit die seitens der die Bundesrepublik Deutschland als EG-Mitgliedsstaat eingegangenen Verpflichtung zur Einhaltung des Parameterwertes für Blei nicht erfüllt werden kann. Ein Verbot für Bleileitungen würde die Einhaltung des Parameterwertes ermöglichen, Rechtsklarheit sowohl für die Verbraucher als auch für die Eigentümer von Hausinstallationen bringen, erhebliche Mittel für Untersuchungs- und Verwaltungskosten einsparen lassen, die ohnehin unumgängliche Sanierung von bleihaltigen Hausinstallationen für die Eigentümer besser planbar machen sowie Rechtsstreitigkeiten über die Interpretation von Meßwerten vermeiden.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001030050220
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  • 4
    Electronic Resource
    Electronic Resource
    Effects of experimental chemoendocrine therapy with a combination of a pure antiestrogen and 5-fluorouracil on human breast cancer cells implanted in nude mice (1999)
    Springer
    Surgery today 29 (1999), S. 149-156 
    Details
    ISSN: 1436-2813
    Keywords: chemoendocrine therapy ; pure antiestrogen ; 5-fluorouracil ; nude mouse ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The antitumor effects of an experimental chemoendocrine therapy combining a new pure antiestrogen ICI 182780 and 5-fluorouracil (5-FU) were studied on MCF-7 human breast cancer cells implanted in nude mice. ICI 182780 had a dose-dependent antitumor activity, which was potentiated by the concomitant use of 5-FU. When compared with the control group, the estrogen receptor (ER) level in the ICI 182780 group was lower and that in the combination group was markedly lower. Cell cycle analysis by flow cytometry (FCM) resulted in a lower percentage of S-phase cells (%S) in the treated mice. No significant difference was observed in the 5-FU concentrations in tumor cells, while the 5-FU content in RNA was significantly higher in the combination group. The changes in free thymidylate synthetase (TS) concentration indicated TS synthesis after the administration of 5-FU to be more greatly suppressed in the combination group than in the 5-FU group. These results suggest that ICI 182780 and 5-FU exert their combination effect mainly on ER-positive cells, and that the suppression of TS synthesis in tumor cells and the potentiation of the 5-FU-induced metabolic dysfunction of RNA are thus involved in the mode of action of this combination therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02482240
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  • 5
    Electronic Resource
    Electronic Resource
    Vinorelbine as first-line chemotherapy for advanced breast cancer in women 60 years of age or older (1999)
    Springer
    Annals of oncology 10 (1999), S. 397-402 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; old age ; vinorelbine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Older patients with advanced breast cancer are less likely to receive chemotherapy than younger patients. Vinorelbine is an attractive alternative in this setting because of its clinical activity and low frequency of side effects. This multicenter, phase II trial was designed to assess the safety and efficacy of intravenous vinorelbine as first-line therapy in women ≥60 years old. Patients and methods: Fifty-six women (median age, 72 years; range 60–84 years), with measurable advanced breast cancer and no prior chemotherapy for metastatic disease, were enrolled and included in the analysis. Vinorelbine 30 mg/m2 was administered weekly for 13 weeks and then every two weeks until development of progressive disease; doses were reduced or delayed to manage toxicity. Results: The objective response rate was 38% (95% confidence interval (95% CI): 24%–51%); median duration of response, nine months; median time to disease progression in all patients, six months. The major dose-limiting toxicity was hematologic, which led to a median dose intensity of 20.6 mg/m2/week. Grade 3–4 nonhematologic toxicity consisted of asthenia (7%); nausea and generalized pain (5%); vomiting, chest pain, abdominal pain, and elevated AST (4%); fever, diarrhea, constipation, and injection site reaction (2%). Neurotoxicity and alopecia were grade 1–2 and relatively infrequent. Conclusions: Vinorelbine offers a promising alternative for the management of advanced breast cancer in elderly patients who are concerned about the subjective side effects of cytotoxic chemotherapy. The dose-limiting toxicity is neutropenia, which is readily managed with dose adjustment. Nonhematologic toxicity, including gastrointestinal side effects, is minimal. Randomized studies are warranted to compare the activity of vinorelbine with that of other regimens in elderly patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008364222793
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  • 6
    Electronic Resource
    Electronic Resource
    Therapie des Knorpelschadens (1999)
    Springer
    Arthroskopie 12 (1999), S. 279-288 
    Details
    ISSN: 1434-3924
    Keywords: Schlüsselwörter ; Knorpelschaden ; Knie ; Knorpelregeneration ; Key words ; Cartilage damage ; Knee ; Cartilage regeneration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Damage to articular cartilage is a common problem. Damage to a joint surface can lead to premature arthritis. In this review the results of the different forms of therapy for cartilage damage such as lavage, drilling, microfracturing, abrasion arthroplasty, transplantation of osteochondral allografts, periosteal arthroplasty and autologous chondrocyte transplantation are introduced to the reader.
    Notes: Die Therapie des Knorpelschadens stellt ein allgemeines Problem dar. Beschädigte Knorpeloberflächen können zur frühzeitig auftretenden Arthrose führen. In dieser Übersichtsarbeit werden die einzelnen Therapieformen zur Behandlung von Knorpelschäden wie die Lavage, Knochenmarkstimulationstechniken (subchondrale Bohrung, Mikrofrakturierung, Abrasionsarthroplastik) sowie neuere Therapieformen wie die Transplantation autologer Knochen-Knorpel-Zylinder, die Periostlappenplastik und die autologe Chondrozytentransplantation mit bisherigen Ergebnissen vorgestellt. Der Leser soll somit einen Überblick über diese Verfahren erhalten.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001420050103
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  • 7
    Electronic Resource
    Electronic Resource
    Einfluß von zyklischer mechanischer Dehnung auf die Zellproliferation humaner Fibroblasten (1999)
    Springer
    Arthroskopie 12 (1999), S. 289-293 
    Details
    ISSN: 1434-3924
    Keywords: Schlüsselwörter ; Rehabilitation ; Humane Fibroblasten ; Zyklische mechanische Dehnung ; Zellproliferation ; Key words ; Rehabilitation ; Human fibroblast ; Cyclic strain ; Cell proliferation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Experimental and clinical studies document the benefits of early controlled motion and loading in the treatment of musculoskeletal injuries. At the cellular level, dynamic strain plays a key role in cell stimulation and organization of the extracellular matrix. Although the positive effects of physical strain on tendon tissue are well known, little knowledge exists as to how mechanical strain affects tendon cells. The aim of the present study was to investigate in vitro the influence of cyclic strain on cell proliferation of human tendon fibroblasts. Human tendon fibroblasts from patellar tendon were cultured on silicone dishes. Cyclic biaxial strain was applied to the dishes in their long axis with third passage cells. A 5% strain magnitude and a frequency of 1 Hz were applied. The time of applied strain varied between 15, 30 and 60 min. After the fibroblasts were put under strain, the cells were tested for proliferation after 6, 12 and 24 h using incorporation of 5-bromo-2′-deoxy-uridine. As a control, cells were grown on silicone dishes but did not receive any strain. A biphasic response in proliferation was observed for the 15- and 60-min strain periods. At 6 and 24 h the proliferation was increased compared to the controls. The proliferation was decreased at 12 h. After a strain duration of 30 min the proliferation was inferior to that of the controls at all times measured. Application of mechanical stress to tendon fibroblasts results in an alteration of cellular proliferation, depending on the stress time. This study will contribute to an understanding of the cellular mechanism underlying the mechanical stimulation of tendon and ligament healing.
    Notes: Klinische und tierexperimentelle Studien haben den positiven Einfluß einer frühfunktionellen Behandlung nach Verletzungen des Binde- und Stützgewebes gezeigt. Dehnung ist dabei der zentrale Stimulus für reaktive Prozesse auf zellulärer Ebene. Zyklische mechanische Dehnung führt zu einer Reihe von Reaktionen, die für die Adaption von Zellen und Geweben an unterschiedliche Belastungen und für den Heilungsprozeß von Bedeutung sind. Ungeklärt ist jedoch, wieviel Dehnungsstreß notwendig ist. Ziel dieser Studie war, den Einfluß der Dauer von definierter zyklischer Dehnung auf die Zellproliferation von humanen Fibroblasten zu untersuchen. Fibroblasten wurden dazu aus Patellarsehnen isoliert und auf Silikonschalen kultiviert. Die Silikonschalen mit Zellen der 3. Passage wurden mit einem elektromechanischen Stimulationsgerät zyklisch mechanisch in der Längsachse gedehnt. Eine Dehnungsamplitude von 5% und die Frequenz 1 Hz wurden für alle Experimente gewählt. Die Dauer der zyklischen Dehnung wurde mit 15, 30 und ¶60 min verändert. Nach insgesamt 6, 12 und 24 h wurde der Versuch beendet. Zur Quantifizierung der Zellproliferation wurde die DNA-Synthese, d. h. der ¶Einbau von 5-Bromo-2′-deoxy uridine¶(BrdU) in die DNA gemessen. Als Kontrolle dienten humane Fibroblasten auf Silikonschalen ohne mechanische Dehnung. Nach 15 und 60 min zyklischer Dehnung zeigte sich ein biphasischer Verlauf hinsichtlich der Zellproliferation. Nach 6 und 24 h war eine Zunahme der Zellproliferation im Vergleich zu 12 h vorhanden. 30 min zyklische mechanische Dehnung hatte im Vergleich zur Kontrolle dagegen keinen positiven Einfluß auf die Zellproliferation. Zyklische mechanische Dehnung führt in Abhängigkeit von der Streßdauer zu Veränderungen bei der Zellproliferation. Die längere Streßdauer induziert potentiell Reaktionen, die eine protektive Wirkung für die Zellproliferation haben. Die zelluläre Streßantwort basiert jedoch auf komplexen Prozessen, deren Regulation und Modulation noch nicht geklärt sind. Das Verständnis der zellulären Reaktionen auf mechanische Dehnung ist von grundlegender Bedeutung für eine funktionelle Behandlung von Sehnen- und Bandverletzungen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001420050104
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  • 8
    Electronic Resource
    Electronic Resource
    Analyse traumatischer und degenerativer Knorpelläsionen des Kniegelenks (1999)
    Springer
    Arthroskopie 12 (1999), S. 294-298 
    Details
    ISSN: 1434-3924
    Keywords: Schlüsselwörter ; Knie ; Knorpelläsion ; Arthroskopie ; Knorpeltransplantation ; Key words ; Knee ; Cartilage lesion ; Arthroscopy ; Cartilage transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: The clinical application of cartilage repair procedures is currently being discussion. To define cartilage lesions with respect to localization, degree of cartilage damage, size, and etiology we retrospectively reviewed data from 4408 patients who had knee arthroscopies. Chondral lesions were divided into traumatic (n = 572, mean age 30.2 years; 13.2–52.7 years) and degenerative (n = 976, mean age 51.4 years; 27.1–79.9 years) lesions. All traumatic cartilage lesions were associated with isolated anterior cruciuate tear. The time interval between injury and arthroscopy was subdivided in patients with acute ¶anterior cruciate ligament tear (〈 6 weeks) or with chronic joint instability (〉 6 weeks). Isolated degenerative cartilage lesions were subdivided in patients aged ≤ 40 years and 〉 40 years. Patients with other associated lesions were excluded. Because we believe that patients with grade III cartilage lesions under the age of 40 years represent the ideal type of patient to receive cartilage or osteochondral transplantation, the data set was analyzed further to characterize these patients. In both groups (traumatic and degenerative) the medial femoral condyle and the medial tibial plateau were most affected. Grade III lesions increased in number and size in all compartments with age by about 2–3.5-fold. The medial tibial plateau showed a significantly higher alteration of about 13-fold in patients aged 〉 40 years. The two subgroups comprising acute and chronic anterior cruciate ligament tears did not demonstrate any statistically significant differences in any parameter. Potential candidates for cartilage grafting accounted for 82 patients (5.3%) on the medial femoral condyle and for 33 patients (2.1%) on the medial tibial plateau of all cartilage lesions (n = 1548 in this data set. In conclusion, we found no relationship between time of surgery and degree of traumatic cartilage lesions after anterior cruciate ligament tear. The development of grade III cartilage lesions in patients older than ¶40 years was significantly higher on the medial tibia plateau than in the other compartments. That means that extrinsic factors have more influence on the cartilage damage than genetically determined factors. In respect to the observation that most of the patients achieve a total knee arthroplasty because of osteoarthritis on the medial compartment, all cartilage reconstructive procedures should be focused on the medial compartment.
    Notes: Die Indikation zur Knorpeltransplantation bzw. zum Einsatz anderer biologisch rekonstruktiver Maßnahmen wird kontrovers diskutiert. Zur Bestimmung des Musters der Knorpelschädigungen im Kniegelenk war es Ziel dieser Studie, die Parameter Lokalisation, Schädigungsgrad und Größe in Abhängigkeit von der Ätiologie zu bestimmen. Es wurden 4408 Patienten mit Kniegelenkarthroskopien ausgewertet, bei denen bei 572 Patienten (Durchschnittsalter 30,2 Jahre; 13.2–¶52,7 Jahre) eine traumatische und bei 976 Patienten (Durchschnittsalter 51,4 Jahre; 27,1–79,9 Jahre) eine degenerative Knorpelschädigung vorlag. Den traumatische Knorpelläsionen wurden Patienten mit einem gesicherten Rotationsereignis und einer isolierten assoziierten vorderen Kreuzbandläsion zugeordnet. Diese Gruppe wurde entsprechend dem Zeitintervall zwischen Ereignis und Arthroskopie in akute (〈 6 Wochen) und chronische (〉 6 Wochen) Zustände unterteilt. Den degenerativen Knorpelläsionen wurden Patienten mit einer isolierten Knorpelpathologie zugeordnet und nach dem Lebensalter ¶(≤ 40 Jahre oder 〉 40 Jahre) weiter differenziert. Patienten mit einer zusätzlichen pathologischen Veränderung wurden ausgeschlossen. Sowohl bei traumatischen als auch degenerativen Erkrankungen waren der mediale Femurkondylus und das mediale Tibiaplateau am häufigsten alteriert. Bei der altersabhängigen Untersuchung zeigte sich, daß erwartungsgemäß in allen Kompartmenten die Häufigkeit von Grad-III-Läsionen um den Faktor 2–3,5 zunahm, auf dem medialen Tibiaplateau jedoch um den Faktor 13. Der Vergleich von akuten mit längerzeitig bestehenden traumatischen Knorpelverletzungen erbrachte keinen statistisch signifikanten Unterschied in allen untersuchten Parametern. Insgesamt hatten nur 82 Patienten (5,3%) am medialen Femurkondylus und 33 Patienten (2,1%) am medialen Tibiaplateau eine Grad-III-Läsion, welche potentiell von allen Knorpelschädigungen (n = 1548) für eine Knorpeltransplantation in Frage kommen würden. Zusammenfassend ist zu schlußfolgern, daß ein Einfluß der Zeitdauer nach traumatischer Knorpelläsion mit assoziierter vorderer Kreuzbandläsion auf die untersuchten Parameter in dieser retrospektiven Untersuchung nicht nachgewiesen werden konnte. Die Entwicklung von degenerativ bedingten Grad-III-Läsionen nimmt am medialen Tibiaplateau im Vergleich zu den anderen Kompartmenten nach dem 40. Lebensjahr sprunghaft zu, so daß der Einfluß exogener Faktoren wahrscheinlicher ist als das alleinige Vorliegen einer anlagebedingten Minderbelastbarkeit des Knorpels. Im Zusammenhang mit der Beobachtung, daß die meisten Patienten aufgrund einer Varusgonarthrose endoprothetisch versorgt werden, sollte die Indikation für knorpelrekonstruierende Maßnahmen auf das mediale Kompartment fokusiert werden.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001420050105
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  • 9
    Electronic Resource
    Electronic Resource
    Arthroskopische Lysis und Lavage des Kiefergelenks zur Therapie von Diskusverlagerungen (1999)
    Springer
    Arthroskopie 12 (1999), S. 318-322 
    Details
    ISSN: 1434-3924
    Keywords: Schlüsselwörter ; Discus-articularis-Verlagerungen ; Arthroskopie ; Lysis & Lavage ; Key words ; Discus articularis ; Displacement ; Arthroscopy ; Lysis & Lavage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Displacement of the discus articularis with and without repositioning represents a common pathological alteration of the temporomandibular joint (tmj). The primary clinical symptoms are pain and reduced jaw movement. Particularly in cases of long-term complaints, conservative treatment methods such as splint and physiotherapy often do not produce the desired results. For these patients, arthroscopy combined with lysis and lavage is the treatment of choice for diagnostic as well as therapeutic purposes. In our department we performed this surgery on a total of 23 patients with discus displacement. With this low-risk procedure we achieved a definite improvement in symptoms in 20 patients; 11 of those patients were eventually complaint-free. Additionally, we can report a general improvement in opening the mouth. Except for a slight postoperative soft-tissue swelling, no complications developed. Thus, we can conclude that arthroscopic lysis and lavage, a low-risk and minimally invasive procedure, should be preferred to open arthrotomy in the primary treatment of tmj-displacements.
    Notes: Verlagerungen des Discus articularis mit und ohne Reposition stellen eine oft zu beobachtende pathologische Veränderung des Kiefergelenks dar. Klinisch stehen dabei Schmerzhaftigkeit und Einschränkungen der Unterkieferbewegungen im Vordergrund. Häufig können diese Beschwerden gerade bei längerem Bestehen durch konservative Behandlungsmaßnahmen wie eine Schienen- oder Physiotherapie nur geringfügig beeinflußt werden. Die Arthroskopie eröffnet hier in Kombination mit einer Lysis und Lavage sowohl diagnostische als auch therapeutische Möglichkeiten. An unserer Klinik wurden insgesamt 23 Patienten mit einer Diskusluxation arthroskopiert. Bei 20 Patienten konnte mit diesem risikoarmen Eingriff eine deutliche Besserung der Symptomatik, bei 11 davon sogar eine subjektive Beschwerdefreiheit erzielt werden. Auch funktionell konnte z. B. eine generelle Verbesserung der Mundöffnung erzielt werden. Abgesehen von geringfügigen postoperativen Weichteilschwellungen waren keine Komplikationen zu verzeichnen. Als Konsequenz unserer Ergebnisse sollten die arthroskopische Lysis und Lavage als risikoarmes, minimalinvasives Verfahren bei Diskusluxationen des Kiefergelenks primär einer offenen Arthrotomie vorgezogen werden.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001420050109
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  • 10
    Electronic Resource
    Electronic Resource
    Mittelfristige Ergebnisse nach arthroskopischer Versorgung von skapholunären Bandverletzungen vergesellschaftet mit frischen distalen intraartikulären Radiusfrakturen (1999)
    Springer
    Arthroskopie 12 (1999), S. 313-317 
    Details
    ISSN: 1434-3924
    Keywords: Schlüsselwörter ; Radiusfraktur loco typico ; Skapholunäre Bandverletzungen ; Arthroskopisch assistierte Versorgung ; Mittelfristige Ergebnisse ; Key words ; Distal radius fracture ; Lesions of the scapholunate ligaments ; Wrist arthroscopy ; Midterm results
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Since 1993, 30 patients with acute intraarticular distal radius fractures have been treated under arthroscopic assistance. In 12 patients (40%) concomitant lesions of the intrinsic scapholunate ligaments were diagnosed. According to Geissler we found grade I-tear in one patient, grade II in three, grade III in six and grade IV in two patients. The eight individuals with grade III-and IV-lesions additionally revealed marked instablity intraoperatively. Therefore, operative stabilization was subsequently performed by temporary scapholunate and scaphocapitate arthrodesis. Seven patients out of this group (87.5%) were followed up clinically and radiologically 3 years postoperatively, on average. Clinical examination included range of motion tests and a subjective questionnaire concerning pain and working ability. Objective grip strength was measured using a Jamar tester and compared to the contralateral wrist. Radiological evaluation consisted of the posteroanterior and lateral view as well as stress views in radial and ulnar deviation. Data were evaluated by the Jakim and Cooney scoring system as well as the demerit point system by Gartland and Werley as modified by Sarmiento et al. According to Gartland, 100% of our patients showed an excellent result; these rates were 86% using the Jakim score and 60% using the Cooney scoring system. According to the subjective questionnaire all of the patients revealed an excellent or good result.
    Notes: Seit 1993 wurden an unserer Klinik 30 Patienten mit frischen distalen intraartikulären Radiusfrakturen arthroskopisch assistiert versorgt. Begleitende Verletzungen der skapholunären intrinsischen Bandverbindungen fanden sich bei 12 Patienten (40%). Entsprechend der Einteilung von Geissler fanden wir einmal eine Läsion vom Grad I, 3mal Grad II, 6mal Grad III und 2mal Grad IV. Die 8 Patienten mit den dritt- bzw. viertgradigen Läsionen zeigten intraoperativ zusätzlich eine deutliche Instabilität im Skapholunargelenk (SL-Gelenk), so daß eine temporäre skapholunäre bzw. skaphokapitäre Spickdrahtarthrodese in derselben Sitzung durchgeführt wurden. Aus dieser Gruppe konnten 7 Patienten (87,5%) nach durchschnittlich 3 Jahren klinisch und radiologisch nachuntersucht werden. Die klinische Untersuchung umfaßte ¶den Bewegungsumfang, subjektive Schmerzangaben sowie eine Befragung nach der Beschäftigung. Mittels Jamar-Dynamometer (Cedaron ® ) wurde die objektive Griffstärke beim Faustschluß im Vergleich beider Hände ermittelt. Zusätzlich wurden Röntgenbilder im a.-p.- und seitlichen Strahlengang sowie Streßaufnahmen in Radial- und Ulnarduktion angefertigt. Die erhobenen Daten wurden mittels der Scores von Jakim , Cooney sowie dem nach Sarmiento modifizierten Gartland-Werley-Score evaluiert. Nach Jakim zeigten 86% der Patienten ein sehr gutes oder gutes Resultat, nach Gartland 100% und nach Cooney 60% ein sehr gutes Ergebnis. In der subjektiven Befragung zeigten alle Patienten ein exzellentes oder gutes Ergebnis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001420050108
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  • 11
    Electronic Resource
    Electronic Resource
    Upregulation of basic fibroblast growth factor in breast carcinoma and its relationship to vascular density, oestrogen receptor, epidermal growth factor receptor and survival (1999)
    Springer
    Annals of oncology 10 (1999), S. 707-713 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; fibroblast growth factor ; microvasculature
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Angiogenesis, the process whereby endothelial cells divide and migrate to form new blood capillaries, has been assessed in tumours by measuring microvessel density. High microvessel density is a significant adverse prognostic factor in breast cancer. The angiogenic factor, basic fibroblast growth factor (bFGF), has been associated with tumourigenesis and metastasis in several human cancers. There are few quantitative studies of bFGF expression in normal tissues compared to cancer. Patients and methods: We have measured bFGF levels in 149 human primary breast carcinomas and assessed the findings in relation to microvessel density, oestrogen receptor (ER) and epidermal growth factor receptor (EGFR). Basic FGF levels were measured by ELISA. Western blotting and immunohistochemistry were carreid out to confirm the presence of bFGF. Results: Levels of bFGF were more than 10-fold higher in tumour cytosols compared to reduction mammoplasty tissue and 3-fold compared to non neoplastic cytosols from the same breast as the tumour (P 〈 0.0001). Immunohistochemistry showed bFGF protein was localised exclusively in the stroma whereas no bFGF staining was observed in the epithelial cells. High bFGF levels were significantly related to high ER (P = 0.01). Similarly, high bFGF levels were significantly related to low grade (P = 0.046) and to small tumour size (P = 0.04). No significant relationship was observed between bFGF and microvessel count, EGFR or age. In univariate analysis and in a Cox proportional hazard model bFGF did not reach significance for overall or relapse free survival. Conclusions: Our results show that although bFGF is elevated in breast carcinomas compared to normal breast tissue it is not related to microvessel density and it is not an independent predictor of survival in breast cancer patients. Basic FGF may be one of multiple factors that synergise with other growth factors such as VEGF to enhance angiogenesis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008303614441
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  • 12
    Electronic Resource
    Electronic Resource
    ESTIC position paper: High-dose chemotherapy for breast cancer, investigation should continue (1999)
    Springer
    Annals of oncology 10 (1999), S. 903-905 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; high-dose chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008396811371
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  • 13
    Electronic Resource
    Electronic Resource
    The influence of familial and hereditary factors on the prognosis of breast cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 1163-1170 
    Details
    ISSN: 1569-8041
    Keywords: BRCA1 ; BRCA2 ; breast cancer ; family history ; survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Family history is a well recognized risk factor for breast cancer, but its impact in terms of breast cancer survival is uncertain. The recent identification of breast cancer predisposing genes has provided new clinical insights in this field. Design: English literature identified through Medline between 1976 and February 1999 was reviewed including search terms: breast cancer, survival, prognosis, family history, genetics, BRCA1, BRCA2, and related articles. Results: Publications were divided into three categories.Family history-based studies: eighteen articles were reviewed. Four studies showed a statistically significant better survival in patients with a family history of breast cancer, and two studies demonstrated a significantly worse prognosis in this context. The remaining articles showed no significant difference. Linkage studies: Two studies based on linkage to BRCA1 found that overall survival was better in linked families. A third one concluded to a worse outcome in BRCA2-linked tumors. Mutation-based studies: 10 studies looking at the association between germ-line mutations in BRCA1/BRCA2 and clinical outcomes were reviewed. Eight articles reported no significant difference in outcome, whereas two studies showed a worse outcome in patients with mutations. Conclusions: Conflicting data exist as to whether the prognosis of familial or hereditary breast cancer differs from that of sporadic cases. Some of the discrepancies may be explained by methodological differences or biases. However, no studies showed a survival advantage for BRCA1mutation carriers. This seems to indicate that BRCA1-related breast cancer is not associated with a survival advantage, and that in fact, certain BRCA1 germline mutations confer a worse prognosis. However, to adequately answer this question, more efficient molecular tools to identify all the genetic changes responsible for breast cancer predisposition, and large cohort studies to evaluate their clinical consequences, are needed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008301314812
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  • 14
    Electronic Resource
    Electronic Resource
    Local relapse in primary breast cancer patients with unexcised positive surgical margins after lumpectomy, radiotherapy and chemoendocrine therapy (1999)
    Springer
    Annals of oncology 10 (1999), S. 1451-1455 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; chemotherapy ; margins ; radiotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Inadequate surgical excision with residual involvement of resection margins by tumour after breast conservation results in increased local recurrence rates. To reduce this risk positive margins are, therefore, usually excised. Systemic treatment with tamoxifen or chemotherapy reduces local recurrence, along with radiotherapy. However, no studies to date have examined the correlation between chemoendocrine treatment, together with radiotherapy, and local relapse in patients with unexcised involved resection margins, having had breast conservation treatment. Patients and methods: The histopathology reports were reviewed of 184 patients who were treated from June 1991 to August 1995 within our randomised study of neoadjuvant versus adjuvant chemoendocrine therapy with mitozantrone and methotrexate (2M) ± mitomycin-C (3M) and tamoxifen, used concurrently with radiation following conservation surgical treatment. Histological resection margin was considered positive if ductal carcinoma in situ (DCIS) or invasive carcinoma was present microscopically less than 1mm from the excision margin. Results: Although 38% of patients had unexcised microscopically involved margins, local relapse rate as first site of relapse was only 1.9% after a median follow up of 57 months. There was no difference in distant relapse (P = 0.2) and survival (P = 0.5) between the positive and negative margins groups. Conclusions: The presence of positive unexcised margins does not have a significant effect on outcome in patients who are treated with chemoendocrine therapy together with radiotherapy. Further clinical trials are required.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008371318784
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  • 15
    Electronic Resource
    Electronic Resource
    Docetaxel in the community setting: An analysis of 377 breast cancer patients treated with docetaxel (Taxotere®) in the UK (1999)
    Springer
    Annals of oncology 10 (1999), S. 205-210 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; docetaxel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Given as first- or second-line chemotherapy, docetaxel appears to have great potential in advanced breast cancer. Patients and methods: Three hundred and seventy-seven locally advanced or metastatic breast cancer patients received docetaxel (Taxotere®) as part of a named patient programme under the care of 108 oncologists from 61 cancer units across the UK. The recommended starting dose was 100 mg/m2, but patients at higher risk of toxicity started at 75 mg/m2. All patients received corticosteroid premedication. The modal number of prior chemotherapy regimens was 2 (range 1–7), 342 patients (91%) had at least one prior anthracycline-based regimen. Results: Response was graded according to the managing clinician's best judgement without formal criteria. The overall response rate (ORR) was 46% among the 331 evaluable patients, 46% among the 299 patients who were 'anthracycline resistant' and 35% among the 82 patients who were 'anthracycline refractory' (progressive disease being the best response obtained to the most recent anthracycline containing regimen). One hundred and ninety-three patients started at the full dose of 100 mg/m2 with an ORR of 55% and 129 started at 75 mg/m2 with an ORR of 33%. In October 1997, some two years after the programme had started, 26 of 377 patients were still alive, although no complete remissions have lasted to this date. Kaplan–Meier survival analysis yielded a median survival of 194 days (95% CI: 178–218 days). Haematological parameters were checked before each course of docetaxel and additionally as clinically indicated. The safety data confirmed that docetaxel has a manageable, predictable side effect profile; 29 of 377 (7.7%) patients were hospitalised as a result of neutropenic sepsis. Conclusions: The results of this named patient programme over a two year timespan confirm that docetaxel is an effective chemotherapy option in patients with locally advanced and/or metastatic breast cancer, including an 'anthracycline refractory' population.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008370930599
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  • 16
    Electronic Resource
    Electronic Resource
    Phase II study of epirubicin and vinorelbine with granulocyte colony-stimulating factor: A high-activity, dose-dense weekly regimen for advanced breast cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 937-942 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; dose-intensity ; epirubicin ; G-CS/kwd〉 ; vinorelbine ; weekly schedule
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: This study was designed to explore the effectiveness and tolerability of a weekly regimen of epirubicin and vinorelbine plus granulocyte colony-stimulating factor (G-CSF). Patients and methods: Fifty-two patients with previously untreated advanced breast cancer were treated with epirubicin (25 mg/m2/week) and vinorelbine (25 mg/m2/week) with G-CSF support, for 24 consecutive weeks. Results: The median number of courses per patient was 22 (range 10–24). The administered dose intensity was 23 mg/m2 for both epirubicin and vinorelbine. Ten complete responses (19%) and 30 partial responses (58%) were obtained, for an overall response rate of 77%. None of the patients progressed during treatment. The median response duration and time to progression were both 10 months. A total of 1065 courses were assessed for toxicity. Grade 3 neutropenia was the most common toxic manifestation, (39% of patients), without febrile neutropenia or neutropenic sepsis. Two patients had grade 3 cardiac toxicity, which regressed without sequelae. Median survival was 31 months, with a median follow-up of 24 months (range 9–40). Conclusions: Owing to its effectiveness and tolerability, the weekly regimen of epirubicin and vinorelbine plus G-CSF may represent an acceptable alternative for patients with untreated metastatic breast cancer. It could be tested in the adjuvant and neoadjuvant setting.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008324329562
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  • 17
    Electronic Resource
    Electronic Resource
    Paclitaxel by 24-hour infusion with doxorubicin by 48-hour infusion as initial therapy for metastatic breast cancer: Phase I results (1999)
    Springer
    Annals of oncology 10 (1999), S. 403-411 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; doxorubicin ; paclitaxel-anthracycline combination ; schedule
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: We and others have demonstrated the antineoplastic efficacy of paclitaxel as a single agent in metastatic breast cancer. We performed this phase I trial to evaluate the combination of paclitaxel with doxorubicin. Patients and methods: Eligible patients had measurable or evaluable metastatic breast cancer for which this was the initial cytotoxic treatment. They may have received adjuvant chemotherapy with other drugs. The study had four parts. In part 1, the patients received paclitaxel by 24-hour infusion followed by doxorubicin by 48-hour infusion. The paclitaxel dose was to be escalated from a starting dose of 125 mg/m2, and the doxorubicin dose was to remain constant at 60 mg/m2 with treatment repeated every three weeks. The results of part 1 prompted part 2 which was a study of the reverse sequence. Part 3 was a formal study of pharmacology and has been reported (J Clin Oncol 14: 2713–21, 1996). In part 4, patients received doxorubicin 50 mg/m2 by bolus followed by paclitaxel 150 mg/m2 by 24-hour infusion for courses 1 and 2. In all subsequent courses doxorubicin was administered by 48-hour infusion. All patients in all four parts of the study had baseline cardiac scans. All patients received standard premedication for paclitaxel. Results: Forty-eight patients were treated in all four parts of the study. In part 1 (10 patients), the maximum tolerated dose (MTD) was paclitaxel 125 mg/m2/24 hours followed by doxorubicin 48 mg/m2/48 hours as defined by dose-limiting mucositis and neutropenic fever which occurred at the starting dose. For part 2 (21 patients), the MTD was doxorubicin 60 mg/m2/48 hours followed by paclitaxel 160 mg/m2/24 hours. In part 4 (seven patients), the MTD was doxorubicin 50 mg/m2/bolus followed by paclitaxel 135 mg/m2/24 hours. In parts 2 and 4, the dose-limiting toxic effect was neutropenia. Of the entire cohort of 48 patients, seven (15%) had a complete response (one persists at five years without intervening therapy), 26 (54%) had a partial response for an objective response rate of 69% (95% confidence interval (95% CI): 54%–81%). The median follow-up of all living patients is 38+ months (range 20+ to 62+); the median response duration is seven months (range 2–33.7+); the median overall survival is 20.5 months (range 5–54+). The median time to progression is 9.6 months (range 1–33.7+ months). Two patients developed congestive heart failure, one at 24 months after her final dose of doxorubicin which amounted to a cumulative lifetime total doxorubicin dose of 870 mg/m2, one after a total of 660 mg/m2. In both, cardiac symptoms were controlled with medications. Conclusions: The combination of paclitaxel/24 hours with doxorubicin/48 hours is an effective antineoplastic treatment for metastatic breast cancer. However, the incidence of complete response, the median overall survival, and time to progression were not greater than for standard doxorubicin-based combinations. Additionally, a sequence-dependent interaction between paclitaxel and doxorubicin, given in the schedule described here, was defined. Other strategies and schedules should be evaluated to maximize the antineoplastic efficacy of these two potent agents.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008360406322
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  • 18
    Electronic Resource
    Electronic Resource
    Primary chemotherapy in operable breast cancer with favorable prognostic factors: A pilot study evaluating the efficacy of a regimen with a low subjective toxic burden containing vinorelbine, 5-fluorouracil and folinic acid (FLN) (1999)
    Springer
    Annals of oncology 10 (1999), S. 993-996 
    Details
    ISSN: 1569-8041
    Keywords: 5-fluorouracil ; breast cancer ; neoadjuvant ; primary chemotherapy ; vinorelbine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Biological considerations support the use of primary chemotherapy in operable breast cancer; and despite wide variations of used regimens, clinical studies consistently show a significant tumor response allowing breast conservation in many patients otherwise canditates for mastectomy. We investigated the efficacy and the acceptance of a combination chemotherapy with vinorelbine, 5-fluorouracil and high-dose folinic acid in operable breast cancer with favorable prognostic factors and tested the relationship of hormone receptor status, Ki67, p53, c-erbB2 and bcl-2 with treatment response. Patients and methods: Thirty-nine patients (median age 51 years, range 36–71 years), eight with T1, twenty-eight with T2 and two with T3 lesions, were treated with 5-fluorouracil (350 mg/m2, i.v. on day 1 to 3) preceded by folinic acid (100 mg/m2 i.v. on day 1 to 3) and vinorelbine, given on days 1 and 3 at the dose of 20 mg/m2 (FLN regimen). Therapy was administered on an outpatient basis every three weeks. Non responders had surgery after three courses, while complete or partial responders underwent surgery after six courses. All but one were evaluable for response and toxicity. Results: Objective responses were observed in 23 of the 38 evaluable patients (61%; 95% CI: 46%–76%): three complete responses (8%) and 20 partial responses (53%). Fifteen patients (39%) had stable disease, of whom nine (23%) had minor response. None of the patients had disease progression during treatment. Objective responses were significantly associated with no expression of estrogen and/or progesteron receptors and 〉50% decrease in Ki67 after induction chemotherapy. Tolerance was excellent and none of the patients experienced grade 2 alopecia. Conclusions: The ‘moderate’ efficacy of this regimen might be partially due to the selection of patients with high expression of steroid hormone receptors and low proliferation rate, which have an unfavorable impact on response to this chemotherapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008389106575
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  • 19
    Electronic Resource
    Electronic Resource
    Cardiac effects of high-dose epirubicin and cyclophosphamide in women with poor prognosis breast cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 53-58 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; cardiotoxicity ; cyclophosphamide ; epirubicin ; high dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To prospectively evaluate the long term cardiac effects of high-dose epirubicin and cyclophosphamide given to women with early stage, poor prognosis breast cancer. Patients and methods: Women with stage 2 breast cancer and 10+ nodes or 4+ nodes and estrogen receptor negative tumor, or stage 3 breast cancer received three cycles of epirubicin 200 mg/m2 and cyclophosphamide 4 gm/m2 with peripheral blood progenitor cell and filgrastim support. Treatment was given every 28 days (n = 79) or 21 days (n = 20). Fifty patients received radiotherapy to the chest wall or breast, 25 of to the left side. Patients were assessed clinically regularly during chemotherapy and at least three times yearly after completion of treatment. Cardiac left ventricular ejection fraction (LVEF) was assessed by radionuclide scan before therapy, after each cycle of chemotherapy, three months and six months after completion of chemotherapy, and yearly thereafter until relapse. Results: Ninety-nine women were treated, and 92 completed all three cycles of chemotherapy. The median age was 43 years (range 24 to 60 years). All patients were included in this analysis. The median relapse-free survival was 39 months (11 to 68 months). There was a significant fall in LVEF during chemotherapy. In general, there was no further deterioration in cardiac function from the third month after cessation of treatment, however there was substantial variation between individuals. 35 patients had at least one LVEF measure less than normal (〈50%), but the LVEF returned to normal in 20 of these with further follow-up. Cardiac dysfunction was not increased in women who received radiotherapy and was not different between cohorts given chemotherapy every three or every four weeks. One patient died of acute myocardial necrosis following the third cycle of chemotherapy. Two patients developed clinical evidence of cardiac failure, and another had radiological signs but was asymptomatic. One woman died of progressive cardiac failure, one recovered clinically but also developed recurrent breast cancer, while the third recovered after commencement of medical therapy. Conclusions: During follow-up after high-dose epirubicin and cyclophosphamide as delivered in this study, the LVEF fell to below normal in approximately one third of patients. However, in over half of these patients the LVEF subsequently recovered to the normal range, and the incidence of clinically evident chronic cardiac failure was low. Further follow-up is required to assess the long- term safety. A randomized comparison with standard-dose anthracycline-based chemotherapy is needed to determine whether this regimen is associated with an increased risk of clinical cardiac toxicity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008390203340
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  • 20
    Electronic Resource
    Electronic Resource
    Analysis of otolith chemistry in Nassau grouper (Epinephelus striatus) from the Bahamas and Belize using solution-based ICP-MS (1999)
    Springer
    Coral reefs 18 (1999), S. 171-178 
    Details
    ISSN: 1432-0975
    Keywords: Key words Otolith ; Chemistry ; ICP-MS ; Stock discrimination ; Epinephelus striatus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Geosciences
    Notes: Abstract  We examined the utility of otolith minor and trace element chemistry, assayed with inductively coupled plasma mass spectrometry (ICP-MS), as a means of delineating population structure in the Nassau grouper (Epinephelus striatus). We characterized the elemental composition of otoliths collected in 1993 from three locations in Exuma Sound, Bahamas and from Glover Reef, Belize in 1995. A single location in Exuma Sound was sampled in 1994 to test temporal variability in otolith composition. Five elements (Ca, Zn, Sr, Ba and Pb) were routinely detected, at levels significantly above background, by solution-based ICP-MS. Results from analysis of variance of elemental data, expressed as a ratio to Ca, indicated that there were no significant differences among the Exuma locations for any element, but significant variability was found between Glover Reef and the pooled Exuma localities for Zn/Ca, Sr/Ca and Ba/Ca ratios. Significant inter-annual differences at one Exuma Sound location was restricted to Ba/Ca ratios. Discriminant function analysis correctly classified 86% and 95% of the Belize and pooled Exuma sites, respectively. Otoliths from Belize were characterized by low Zn/Ca and high Ba/Ca and Pb/Ca ratios compared to otoliths from fish collected in Exuma Sound. Although differences in Ba levels may be related to upwelling at Glover Reef, more data are needed to definitely link otolith composition with regional differences in water chemistry.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003380050176
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  • 21
    Electronic Resource
    Electronic Resource
    Wertigkeit der MRT bei traumatischer diskoligamentärer Instabilität der unteren HWS (1999)
    Springer
    Der Unfallchirurg 102 (1999), S. 942-948 
    Details
    ISSN: 1433-044X
    Keywords: Schlüsselwörter ; HWS • Diskoligamentäre Instabilität • Funktionsaufnahmen • MRT ; Key words ; Lower cervical spine • Traumatic discoligamentous instabilities • Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The diagnostic accuracy of magnetic resonance imaging (MRI) for traumatic discoligamentous instabilities of the lower cervical spine was evaluated. MRI findings were correlated with the intraoperative findings. Fifteen patients were included in the study (11 males, 4 females, 33 years old on average). Indication for surgery was established with dynamic a. p. instability under fluoroscopy. In the operation, all patients showed complete traumatic rupture of the intervertebral disc. In contrast, MRI sequences revealed only eight mild and four severe disc lesions. Intraoperatively ruptures of the anterior and posterior longitudinal ligaments were verified in 7 patients each. MRI studies depicted only five ruptures of the anterior and three ruptures of the posterior longitudinal ligaments. In three cases MRI demonstrated no pathological findings (3 of 15 false-negative results). MRI and intraoperative findings showed no statistical correlation. MRI is of only limited value in diagnosing traumatic discoligamentous instabilities of the lower cervical spine.
    Notes: Zusammenfassung Die diagnostische Aussagekraft der Magnetresonanztomographie (MRT) bei frischer, traumatischer diskoligamentärer Instabilität der unteren Halswirbelsäule (HWS) wurde untersucht. Hierzu wurden die Befunde der MRT-Diagnostik mit den intraoperativen Befunden korreliert. Die Indikation zur Operation wurde bei nachgewiesener translatorischer a.-p.-Instablität im Röntgenbildwandler bei dynamischer Untersuchung gestellt; 15 Patienten (11 Männer, 4 Frauen, Durchschnittsalter 33 Jahre) wurden in die Studie eingeschlossen. Bei allen Patienten lag intraoperativ eine Ruptur des Discus intervertebralis vor. In der MRT-Diagnostik wurden hingegen bei 8 Patienten eine Bandscheibenprotrusion und bei 4 Patienten ein Bandscheibenprolaps nachgewiesen. Das vordere Längsband und das hintere Längsband waren intraoperativ bei jeweils 7 Patienten rupturiert. Im MRT-Befund war das vordere Längsband bei 5 Patienten und das hintere Längsband bei 3 Patienten rupturiert. Bei 3 von 15 Patienten (20 %) war die MRT unauffällig und damit falsch-negativ. Zwischen intraoperativem und MRT-Befund war keine statistisch signifikante Korrelation nachweisbar. Die MRT bietet daher für die Indikationsstellung zur Operation zum jetzigen Zeitpunkt keine ausreichende diagnostische Sicherheit bei der Evaluation traumatischer diskoligamentärer Instabilitäten der unteren HWS.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001130050508
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  • 22
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    Electronic Resource
    Einfache und schnelle Methode zur Entfernung abgebrochener, unaufgebohrter Tibianägel (1999)
    Springer
    Der Unfallchirurg 102 (1999), S. 975-978 
    Details
    ISSN: 1433-044X
    Keywords: Schlüsselwörter ; Implantatversagen • UTN • Entfernung des distalen Nagelanteils ; Key words ; Breakage of UTN • Extraction device
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary By using UTN in the treatment of very distal tibia fractures delayed fracture-healing and pseudarthrosis with breakage of the nail are described. The removal of the distal solid part of the nail shows a special difficulty. We report about two cases of broken UTN in 1997. A simple extraction device to remove the distal part of the broken nail is demonstrated.
    Notes: Zusammenfassung Mit der Anwendung des unaufgebohrten Tibianagels (UTN) bei sehr distalen Tibiafrakturen wird zunehmend von verzögerter Knochenbruchheilung und Pseudarthrosen mit nachfolgendem Implantatversagen berichtet. Die Entfernung des soliden, distalen Nagelteils bringt besondere Schwierigkeiten mit sich. 1997 wurden in der BG-Unfallklinik Ludwigshafen 2 gebrochene, unaufgebohrte Tibianägel entfernt. Der Behandlungsverlauf sowie ein einfaches, überall verfügbares Verfahren zur zuverlässigen Entfernung des distalen Nagelanteils werden beschrieben.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001130050513
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  • 23
    Electronic Resource
    Electronic Resource
    Bloom-Syndrom Ein erbliches Kleinwuchssyndrom (1999)
    Springer
    Monatsschrift Kinderheilkunde 147 (1999), S. 1014-1017 
    Details
    ISSN: 1433-0474
    Keywords: Schlüsselwörter Bloom-Syndrom ; Chromosomeninstabilität ; Kleinwuchs ; Wachstumshormon ; Key words ; Bloom’s syndrome ; Chromosomal instability ; Growth retardation ; Growth hormone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Bloom’s syndrome is a rare condition which is doubtlessly underdiagnosed. It is characterized by pre- and postnatal growth deficiency, cutaneous lesions, a recognizable facial dysmorphism, recurrent infections and an excessive risk of cancer. The pathogenetic basis is a significantly increased genomic instability. Bloom’s syndrome is transmitted as an autosomal-recessive trait. The responsible gene has been identified recently. We report on a 4 year old Turkish girl with Bloom’s syndrome confirmed by an increased sister chromatid exchange rate. She came to our attention because of severe growth deficiency, but lacked the cutaneous signs. Discussion: Our report emphasizes that Bloom’s syndrome has to be considered in children presenting with proportionate short stature, even in the absence of the full clinical phenotype.
    Notes: Zusammenfassung Das Bloom-Syndrom ist eine seltene, zweifellos aber auch zu selten diagnostizierte Entität. Es ist gekennzeichnet durch prä- und postnatale Wachstumsverzögerung, Hautveränderungen, eine diskrete, aber typische faziale Dysmorphie, gehäufte Infektionen und – prognostisch am bedeutsamsten – ein hohes Malignomrisiko. Der zugrundeliegende Defekt ist eine erhöhte DNA-Instabilität. Der Erbgang ist autosomal-rezessiv; das Gen ist seit kurzem bekannt. Wir berichten über ein 4jähriges türkisches Mädchen mit den Leitsymptomen Kleinwuchs und Dystrophie, bei dem die Diagnose anhand der erhöhten Schwesterchromatidaustauschrate gesichert werden konnte. Das Kind hatte nicht die typischen Hautveränderungen. Diskussion: Der Fallbericht verdeutlicht, daß das Bloom-Syndrom in die Differentialdiagnose des proportionierten Kleinwuchses einbezogen werden muß, auch wenn nicht das Vollbild der Erkrankung vorliegt.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001120050533
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  • 24
    Electronic Resource
    Electronic Resource
    Die Lisfranc-Arthrodese nach Fehlheilung (1999)
    Springer
    Der Unfallchirurg 102 (1999), S. 918-923 
    Details
    ISSN: 1433-044X
    Keywords: Schlüsselwörter ; Fehlheilung • Posttraumatische Arthrose • Lisfranc-Luxationsfrakturen • Lisfranc-¶Arthrodese • Maryland-Foot-Score ; Key words ; Residual deformity • Posttraumatic arthritis • Lisfranc-fracture-dislocation • Lisfranc Arthrodesis • Maryland Foot Score
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The causes of residual deformity with posttraumatic painful arthritis after tarsometatarsal (Lisfranc) fracture-dislocation with the need for correctional arthrodesis are in our experience (22 cases over 5 years) overseen injuries in one third, closed reduction and immobilisation or inadequate fixation technique with K-wires in another two thirds of cases. Foot malalignment and residual instability is assessed with weight-bearing radiographs of both feet, adduction/abduction stress films and CT scans for complex deformity. Correction is carried out via two longitudinal dorsal incisions, strict epiperiosteal preparation and debridement of the Lisfranc joint of all remaining cartilage, sclerosis and fibrous tissue. Reorientation begins, in the same manner as primary open reduction, with anatomical alignment of the second metatarsal base to the second cuneiform. Defects are filled with autologous bone grafting, stable fusion can be achieved with 3.5 mm cancellous compression screws. Full weight bearing is allowed in a modelled plaster shoe for 6 to 8 weeks. The functional medium-term results are convincing with 15 of 17 patients seen after 13 months of follow-up working full time. The Maryland Foot Score improved from 38.9 to 76.8 points in these patients.
    Notes: Zusammenfassung Fehlverheilungen mit konsekutiver posttraumatischer Arthrose nach Lisfranc-Luxationsfrakturen mit notwendiger reorientierender Lisfranc-Arthrodese gehen nach eigener Erfahrung (22 Fälle in 5 Jahren) in 1/3 der Fälle auf übersehene Verletzungen, in 2/3 der Fälle auf unzureichende geschlossene Repositionen und perkutane Spickdrahtosteosynthesen oder alleinige Retention im Gipsverband zurück. Belastungsaufnahmen beider Füße in 2 Ebenen sind zur Erkennung der Instabilität und Fehlverheilung unerläßlich, gegebenenfalls Vorfußabduktions- bzw. Adduktionsaufnahmen, eine Tomographie oder ein CT in 2 Ebenen. Bei veralteter homolateraler Lisfranc-Luxationsfraktur ist über 2 dorsale Längsinzisionen bei streng epiperiostaler Präparation das gesamte Lisfranc-Gelenk auszuräumen. Die Reorientierung beginnt – wie bei frischer Verletzung mit der anatomischen Einpassung der Metatarsale-II-Basis zum Cuneiforme II. Defekte sind mit autologer Spongiosa aufzufüllen, die Arthrodese mit 3,5er Kortikaliszugschrauben ist ausreichend. Die Nachbehandlung im Gipsschuh für 6–8 Wochen mit Vollbelastung hat sich bewährt. Der funktionelle Gewinn nach reorientierender Lisfranc-Arthrodese ist nach dem Maryland-Foot-Score von präoperativ 38,9 auf 76,8 Punkte postoperativ überzeugend.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001130050506
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  • 25
    Electronic Resource
    Electronic Resource
    Spontanheilung einer juvenilen Knochenzyste der Tibia nach pathologischer Fraktur (1999)
    Springer
    Der Unfallchirurg 102 (1999), S. 972-974 
    Details
    ISSN: 1433-044X
    Keywords: Schlüsselwörter ; Juvenile Knochenzyste • Pathologische Fraktur • Konservative Therapie • Spontanheilung ; Key words ; Juvenile bone cyst • Pathological fracture • Conservative therapy • Spontaneous healing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Up to the present only few cases of spontaneous healing of juvenile bone cysts after pathological fractures were published. Most authors will not accept the possibility of a “healing fracture” in bone cysts because of missing documentation. In our clinic we could observe spontaneous healing of a juvenile bone cyst of the tibia after a pathological fracture in a ten-year old boy. Therefore healing of bone cysts after fracture is proven. On the other hand healing of bone cysts following conservative treatment after a fracture is not sure. Conservative treatment depends on the localization and type of the fracture. We recommend nonoperative treatment of first pathological fractures in small-sized bone cysts. This kind of treatment can be especially advised for young patients up to the tenth year because there are only few complications in fracture healing and a relatively high recurrence rate following operative treatment. In case of a refracture there are better conditions for fracture healing after surgery.
    Notes: Zusammenfassung Nach pathologischer Fraktur juveniler Knochenzysten (JKZ) wurde in der Literatur über einzelne Fälle von Spontanheilungen der Zysten im Rahmen der Frakturheilung berichtet. Vollständig dokumentierte Fälle liegen jedoch nicht vor, so daß die Möglichkeit einer sog. „heilenden Fraktur“ von den meisten Autoren nicht akzeptiert oder sogar prinzipiell ausgeschlossen wird. In unserer Klinik wurde eine Spontanheilung einer juvenilen Knochenzyste der Tibia nach pathologischer Unterschenkelfraktur bei einem 10 jährigen Jungen beobachtet. Eine Spontanheilung der JKZ im Rahmen der Frakturheilung ist also sicher grundsätzlich möglich. Eine zuverlässige Ausheilung der Zyste kann allerdings auf konservativem Wege nicht erreicht werden, da die osteolytische Potenz erhalten bleibt. Voraussetzung für ein konservatives Vorgehen ist eine geeignete Frakturlokalistation und -form. Unseres Erachtens ist die konservative Behandlung bei einer erstmaligen Spontanfraktur kleinerer Zysten indiziert. Insbesondere gilt dies für junge Patienten bis zum 10. Lebensjahr, aufgrund des günstigen Frakturheilungspotentials bei gleichzeitig bestehendem hohen Zystenrezidivrisiko trotz operativer Therapie. Im Falle der Refraktur ergeben sich für den dann notwendigen Eingriff evtl. günstigere Voraussetzungen aufgrund der Alterszunahme.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001130050512
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  • 26
    Electronic Resource
    Electronic Resource
    Bedeutung von Begleitverletzungen bei Malleolarfrakturen (1999)
    Springer
    Der Unfallchirurg 102 (1999), S. 949-954 
    Details
    ISSN: 1433-044X
    Keywords: Schlüsselwörter ; Sprunggelenk • Begleitverletzungen •¶Fraktur • Prognose • Knorpelschaden ; Key words ; Ankle • Injury • Fracture • Outcome •¶Cartilaginous lesion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The objective of this prospective study was to determine clinical and radiological results 2 years after ankle fractures and to compare them with preoperative arthroscopic findings. Of 135 consecutive patients undergoing osteosynthetic treatment, 128 (type A, 2; type B, 97; type C, 29) were reviewed 2 years later. The Kitaokascore for functional and clinical rating and the Kannusscore for radiological rating were used. Initial cartilaginous lesions localized on the medial malleolus led to poor clinical ratings (P 〈 0.01) and cartilaginous lesions of the pilon tibiale and talus caused poor radiological results (P 〈 0.032 and P 〈 0.046). After rupture of the deltoid ligament, more pain was observed (P 〈 0.038). Rupture of the syndesmosis, however, did not affect the outcome. Clinical outcome was poor among the 30- to 65-year-old patients. The clinical and radiological outcome of women was poorer (P 〈 0.018 and P 〈 0.046) than for men. The older the patients, the more radiological signs of arthritis were found. The outcome of ankle fracture seems to correlate significantly with the nature, dimension and localization of fracture-associated cartilaginous and ligament lesions. Age and sex also seem to play a significant role in the outcome.
    Notes: Zusammenfassung Die Ziele dieser prospektiven Studie war es, die klinischen und radiologischen Resultate 2 Jahre nach Malleolarfraktur zu bestimmen und diese mit den initialen, arthroskopisch erhobenen Begleitverletzungen nach dem Unfall zu vergleichen. Von 135 konsekutiven Patienten (135 Füsse), die vor der osteosynthetischen Versorgung einer Malleolarfraktur arthroskopisch untersucht wurden, konnten 128 Patienten (Typ A, 2; Typ B, 97; und Typ C, 29) nach durchschnittlich 2 Jahren nachkontrolliert werden. Dabei wurden der Kitaoka-Score (Klinik, Funktion) und der Kannus-Score (Röntgen) verwendet. Initiale Knorpelschäden am medialen Malleolus führten zu einem schlechteren klinischen Resultat (P 〈 0.010), wohingegen Knorpelschäden am Pilon tibiale und Talus ein schlechteres radiologisches Resultat (P 〈 0.032 bzw. P 〈 0.046) zeigten. Nach Ruptur des Lig. deltoideum waren assoziierte Schmerzen gehäuft (P 〈 0.038). Eine Syndesmosenruptur beeinflusste das Resultat nicht. Generell war das klinische Resultat bei den 30- bis 65 jährigen Patienten am schlechtesten und bei Frauen klinisch und radiologisch schlechter als bei Männern (P 〈 0.018 bzw. P 〈 0.046). Die radiologischen Veränderungen nahmen mit dem Alter zu. Das Resultat nach Malleolarfrakturen scheint demnach entscheidend von der Art, Ausmass und Lokalisation der Begleitverletzungen des Knorpels und der Bänder abzuhängen. Daneben könnten Alter und Geschlecht des Patienten präjudizierende Faktoren des Endergebnisses sein.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001130050509
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  • 27
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    Electronic Resource
    Bakterielle Koxitis durch Salmonella enteritidis (1999)
    Springer
    Der Unfallchirurg 102 (1999), S. 967-971 
    Details
    ISSN: 1433-044X
    Keywords: Schlüsselwörter ; Bakterielle Arthritis • Salmonella enteritidis • Hüftgelenk • Pathologische Diagnostik • Therapie ; Key words ; Bacterial arthritis • Salmonella enteritidis • Hip joint • Pathologic diagnosis • Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Secondary haematogenous joint involvement is seen in less than 1 % of patients with Salmonella infections. These atypical infections are frequently encouraged by pre-existing local or systemic disease. We present a case of a patient with known alcohol abuse who developed a septic infection of her right hip requiring resection of the femoral head. Histologic analysis showed signs of pre-existing osteonecrosis probably induced by alcohol intake. Cartilage and bone were invaded and destructed by an aggressive granulation tissue. Initially, a biopsy evaluated without knowledge of the positive bacteriological result had been interpreted as indicative of a tumour. The onset, clinical course, diagnosis and therapy of joint involvement by Salmonella are discussed with regard to our case and the relevant literature. This case illustrates the necessity for clinicians to share all their information about the patient with the pathologist.
    Notes: Zusammenfassung Sekundäre hämatogene Gelenkinfektionen werden bei weniger als 1 % aller systemischen Salmonellosen beobachtet. Lokale Gewebeschädigungen oder systemische Grunderkrankungen begünstigen das Zustandekommen dieser atypischen Infektionen. Wir stellen den Fall einer alkoholabhängigen Patientin dar, bei welcher eine Salmonellenkoxitis auf dem Boden einer ischämischen Knochennekrose des Hüftkopfes entstand. Die weit fortgeschrittene Zerstörung des Gelenks erforderte eine Resektionsarthroplastik. Histologisch fand sich eine destruierende Invasion von Knorpel und spongiösem Knochen durch zellreiches Entzündungsgewebe. In Unkenntnis des bakteriologischen Befundes war zunächst der Verdacht auf eine neoplastische Veränderung geäußert worden. Entstehung, Verlauf, Diagnostik und Therapie der Salmonellenarthritis werden anhand dieses Falles und der Literatur diskutiert. Die erfolgreiche Befundung einer Knochenbiopsie ist auf eine gute Kommunikation zwischen Kliniker und Pathologe angewiesen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001130050511
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  • 28
    Electronic Resource
    Electronic Resource
    Operative Behandlung von Verletzungen des thorakolumbalen Übergangs (1999)
    Springer
    Der Unfallchirurg 102 (1999), S. 924-935 
    Details
    ISSN: 1433-044X
    Keywords: Schlüsselwörter ; Arbeitsgemeinschaft „Wirbelsäule“ der DGU • Thorakolumbale Wirbelsäule • Wirbelsäulenverletzung • Operative Behandlung • Epidemiologie • Magerl-Klassifikation • Querschnittlähmung • Frankel-/ASIA-Score •¶Hannover Wirbelsäulenscore ; Key words ; Working group “spine“ of the German Society of Trauma Surgery • Thoracolumbar spine • Spinal fracture • Injuries of the spine • Operative treatment • Epidemiology • Classification of thoracolumbar spinal injuries by Magerl • Paraplegia • Frankel/ASIA grading system • Hannover Spine Score
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The authors report on a prospective multicenter study with regard to the operative treatment of fractures and dislocations of the thoracolumbar spine. 18 traumatologic centers in Germany and Austria, forming the working group “spine“ of the German Society of Trauma Surgery, are participating in this continuing study. Between September 1994 and December 1996 682 patients (64 % male) with an average age of 391/2 (7–83) years were entered. The entry criteria included all patients with acute and operatively treated (within 3 weeks after trauma) fractures and dislocations of the thoracolumbar spine (Th 10-L 2). Part 1 of this publication outlines the protocol and epidemiologic data. The incidence of fractures and dislocations of the thoracolumbar spine and associated injuries were recorded according to a standardized protocol, as well as the different operative methods and complications, duration of hospital stay, rehabilitation and incapacity. The analysis of the clinical social and radiological course was a second focus. The most frequent mechanism of injury was a fall (50 %) or traffic accident (22 %). Most of the fractures occured at the L 1 level (49 %). All injuries were classified according to the ASIF (AO) classification. 65 % sustained an A-type fracture (compression fracture). Associated injuries were observed in 35 % and 6 % were polytraumatized. Extremities and thorax were most frequently affected. Younger age and traffic accidents lead more often to C-type fracture (fracture dislocation) and polytrauma. An increased number of multisegmental or multilevel lesions were observed in polytraumatized patients. There were 16 % with incomplete paraplegia (Frankel/ASIA B–D) and 5 % with complete paraplegia (Frankel/ASIA A). The rate of patients with initial neurologic deficits significantly increased with the severity of spinal injury according to the Magerl classification. Until discharge a neurologic improvement (at least 1 Frankel/ASIA grade) was observed in 32 % of the partially paralyzed (Frankel/ASIA B–D) and in 12 % of the patients with complete paraplegia (Frankel/ASIA A). A neurologic deterioration occured in 3 patients (0.4 %). As a base for further follow-up and late results the individual starting point was determined by collecting relevant data of the patients' history: 277 (40.6 %) patients suffered from simultaneous diseases, one half was spine related. At the time of injury 559 (82.0 %) patients were employed; 429 (62.9 %) doing manual work. 369 (54.1 %) patients stated sportive activities before the injury and 561 (82.3 %) designated their “back function“ as normal. For the time before injury the patients scored an average of 93.4 points in the Hannover Spine Score (0–100 points concerning complaints and function of the back/spine).
    Notes: Zusammenfassung Die Autoren berichten über eine prospektive, multizentrische Studie zur operativen Behandlung frischer Verletzungen des thorakolumbalen Übergangs der Wirbelsäule. An der noch nicht abgeschlossenen Studie sind insgesamt 18 unfallchirurgische Kliniken in Deutschland und Österreich beteiligt; sie bilden die Arbeitsgemeinschaft „Wirbelsäule“ der Deutschen Gesellschaft für Unfallchirurgie. Von September 1994 bis Dezember 1996 wurden 682 Patienten (64 % männlich) mit einem Durchschnittsalter von 391/2 (7–83) Jahren erfaßt. Die Eingangkriterien schlossen alle Patienten mit frischer und innerhalb von 3 Wochen operierter thorakolumbaler Verletzung (Th 10-L 2) ein. Im Teil 1 des Berichts schildern wir den Aufbau der Studie und epidemiologische Daten. Häufigkeit und Art von Wirbelsäulen- und Begleitverletzungen wurden ebenso einheitlich erfaßt wie Angaben zu den verschiedenen operativen Behandlungskonzepten und Komplikationen, der Dauer der Behandlung, Rehabilitation und Arbeitsunfähigkeit. Die Analyse des klinischen, sozialen und röntgenologischen Verlaufs stellte einen weiteren Schwerpunkt dar. Häufigste Unfallursachen waren Stürze aus der Höhe (50 %) und Verkehrsunfälle (22 %). Der erste Lendenwirbelkörper war mit Abstand am häufigsten betroffen (49 %). Alle Verletzungen wurden nach der AO-Einteilung klassifiziert; 65 % aller Patienten erlitten Kompressionsverletzungen (Typ A). Bei 59 % lag eine isolierte Wirbelsäulenverletzung vor, die übrigen wiesen Begleitverletzungen auf und 6 % waren polytraumatisiert. Begleitverletzungen betrafen am häufigsten Extremitäten und Thorax. Jüngere Patienten und Verkehrsunfallopfer erlitten häufiger eine Rotationsverletzung (Typ C) und waren häufiger polytraumatisiert. Mehrsegment- oder Mehretagenläsionen waren häufiger bei Polytraumatisierten. Eine inkomplette Querschnittläsion (Frankel/ASIA B–D) wiesen 16 %, eine komplette (Frankel/ASIA A) 5 % auf. Der Anteil neurologisch beeinträchtigter Patienten nahm mit der Verletzungsschwere signifikant zu. Bei 32 % der Patienten mit inkomplettter Lähmung besserte sich der neurologische Befund bis zur Entlassung um mindestens 1 Stufe nach dem Frankel-/ASIA-Schema, bei 12 % nach Paraplegie. Zu einer Verschlechterung um mindestens 1 Stufe kam es bei 3 Patienten (0,4 %). Als Grundlage differenzierter Nachuntersuchungsergebnisse wurden Angaben zur individuellen Situation vor dem Unfall erfaßt: 277 (40,6 %) Patienten wiesen Vorerkrankungen auf, etwa die Hälfte davon solche der Wirbelsäule. 559 (82,0 %) Patienten waren zum Zeitpunkt des Unfalls berufstätig; 429 (62,9 %) gingen einer körperlichen Arbeit nach. 369 (54,1 %) Patienten gaben sportliche Freizeitaktivitäten an und 561 (82,3 %) bezeichneten ihre Rückenbeweglichkeit als normal. Im Hannover Wirbelsäulen-Score (0–100 Punkte zu Beschwerden und Funktion) erzielten die Patienten für die Zeit vor dem Unfall im Mittel 93,4 Punkte.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001130050507
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  • 29
    Electronic Resource
    Electronic Resource
    Ersatz des vorderen Kreuzbands in der TransFix®-Technik (1999)
    Springer
    Arthroskopie 12 (1999), S. 305-312 
    Details
    ISSN: 1434-3924
    Keywords: Schlüsselwörter ; Kreuzbandersatzoperation ; Hamstring-Sehnen ; Femorale Fixation ; Tibiale Fixation ; Key words ; Anterior cruciate ligament reconstruction ; Hamstrings ; Femoral fixation ; Tibial fixation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: In recent years ACL reconsruction with the midpatellar tendon has been being called into question more and more because of high morbidity at the harvest site and problems with fixation near the joint. The”wiper effect” or “bungee-effect” may be mentioned as an example. In this paper, ACL reconstruction using the hamstrings is presented, which, in contrast to fixation with the Endobutton, has a very high pull out strength and also tibial fixation near the joint with a biodegradable interference screw. This surgical method has been carefully developed and is technically sophisticated. The technique can be used mainly in younger women with small patellae, athletically inactive persons with a high level of instability, all patients with parapatellar problems or pain, and patients whose occupation involves kneeling. The short-term results are excellent; long-term results with this new method are not yet available. This method should be seen as an alternative to ACL reconstruction with the midpatellar tendon and, in our view, the security of fixation is at least as good as with the Endobutton.
    Notes: In den letzten Jahren wird die Kreuzbandersatzoperation mit dem mittleren Patellarsehnendrittel zunehmend mehr in Frage gestellt. Gründe sind die hohe Transplantatentnahmemorbidität sowie Probleme bei der gelenknahen Fixation. Der Scheibenwischereffekt, der Bungee-Effekt u. a. seien hierfür stellvertretend genannt. Im folgenden wird daher eine Kreuzbandersatzoperationstechnik unter Verwendung der Hamstring-Sehnen vorgestellt, die im Gegensatz zur Fixation über den Endobutton ® eine sehr ausreißfeste femorale Fixation sowie eine ebenfalls gelenknahe tibiale Fixation über eine biodegradierbare Interferenzschraube beinhaltet. Die Operationsmethode ist durchdacht und technisch ausgereift. Indikationen stellen vorwiegend jüngere Frauen mit kleiner Kniescheibe, sportlich wenig aktive Menschen mit hochgradiger Instabilität sowie alle Patienten mit parapatellaren Problemen oder Schmerzen, des weiteren Patienten mit kniender Tätigkeit dar. Die Kurzzeitresultate sind hervorragend, Langzeitergebnisse stehen bei dieser jungen Methode noch aus. Die Methode sollte als Alternativvariante zur Kreuzbandersatzoperation mit dem mittleren freien Patellarsehnendrittel gesehen werden und ist in ihrer Fixationssicherheit aus unserer Sicht dem Endobutton mindestens gleichwertig.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001420050107
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    Electronic Resource
    All-Press-FIT, eine neue Operationsmethode zum vorderen Kreuzbandersatz mit gleichzeitiger femoraler und tibialer Press-Fit-Verankerung (1999)
    Springer
    Arthroskopie 12 (1999), S. 299-304 
    Details
    ISSN: 1434-3924
    Keywords: Schlüsselwörter ; Vorderes Kreuzband ; Rekonstruktion ; Patella-bone-tendon-bone ; Press-fit-Fixation ; All-Press-fit ; Doppelblockfixierung ; Key words ; ACL Reconstruction ; Bone-Patellar-tendon-bone autograft ; Press-fit ; Implant free fixation ; All-Press-Fit-fixation ; Doubleblock fixation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: In the treatment of anterior cruciate ligament reconstruction, bone-patellar-tendon-bone allograft has been developed to a standard. Fixation of the graft with interference screws in the femur and/or with staple in the tibia are usual. ALL-PRESS-FIT fixation makes an implant-free acl-reconstruction possible. The bone-patellar-tendon-bone allograft is harvested with oversized bone blocks. The “Bone-Compactor” is used for modelling the oversized boneblocks for press-fit-fixation in femur und tibia. Implantation can be managed in either an arthroscopic or open procedure. The proximal boneblock is implanted with a sagittal alignment of the tendon. While rotating the distal block 90° to medial, a recontruction of anteromedial und posterolateral fascicle is possible. Tension can be controlled after step-by-step fixation proximal and distally with a distalisation of the tibial block at the end. The prominent tibial block will be pressed in on corticalis-niveau with the “Reconcillation-Hit”. A femoral or tibial “Doubleblock-Fixation” allows a better anatomical reconstruction. A third bone block, harvested from the tibial channel, fixed on the distal ligament, is used to fill up the tibial channel with bone to the tibial plateau. The “tibial doubleblock-fixation” allows a better biomechanical bone fixation of the ligament. Alternatively, a patellar-bone-tendon-bone allograft can be used with a high tibial press-fit fixation with a ligament outlet directly onto the tibia plateau. The proximal boneblock is implanted deep in the whole femur whole and fixed with the third bone block harvested from the tibial channel.
    Notes: Bei der operativen Versorgung der vorderen Kreuzbandruptur hat sich die Verwendung des mittleren Drittels der Patellarsehne als Standard etabliert. Die Knochenblöcke aus Patella und Tibiakopf werden üblicherweise mit Interferenzschrauben oder Staple fixiert. Mit der All-Press-FIT-Verankerung ist eine fremdimplantatfreie femorale und tibiale Verankerung möglich. Der mittlere Sehnenanteil des Lig. patellae wird mit Knochenblöcken aus der distalen Patella und dem Tibiakopf gewonnen. Mit dem Knochenkompaktor, der als Zurichtungsinstrument und Schablone dient, werden die Knochenblöcke in notwendiger Übergröße so zugerichtet, daß sie später femoral und tibial ohne zusätzliche Hilfsmittel press fit verankert werden können. Die Implantation ist sowohl arthroskopisch als auch offen möglich. Der obere Knochenblock wird so eingebracht, daß ein vorderes und hinteres Bündel entsteht. Durch Rotieren des unteren Knochenblocks entsteht ein anteromediales und posterolaterales Bündel. Zur nachträglichen Korrektur der Bandspannung kann der tibiale Knochenblock nach distal ausgetrieben werden. Der Knochenblock wird dann mit dem „Versöhnungsschlag“ auf Kortikalisniveau versenkt. Die femorale oder tibiale „Doppelblockfixierung“ ermöglicht eine anatomiegerechte Rekonstruktion. Ein aus dem Tibiakopf entnommener dritter kortikospongiöser Knochenblock armiert den Ligamentanteil im Tibiakanal für eine bessere knöcherne Führung des Bands. Die so erzielte tibiale Doppelblockfixierung ermöglicht eine anatomiegerechte sagittale Ausrichtung des Ligaments durch eine langstreckige knöcherne Stabilisierung im Tibiaplateau. Alternativ wird der tibiale Knochenblock auf Höhe des Tibiaplateau press fit festgesetzt. Der patellare Knochenblock wird tief in dem femoralen Kanal eingesetzt. Das Ligament wird mit dem Eintreiben des aus dem Tibiabohrkanal gewonnenen Knochenblocks angespannt und femoral gelenknah verankert. Es entsteht die femorale Doppelblockfixierung.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001420050106
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    Long-term application of disease modifying antirheumatic drugs (DMARD). A single-center, observational study of 1681 patients with rheumatoid arthritis (RA) (1999)
    Springer
    Zeitschrift für Rheumatologie 58 (1999), S. 267-276 
    Details
    ISSN: 0340-1855
    Keywords: Key words ; Rheumatoid arthritis ; DMARD therapy ; observation study ; Schlüsselwörter ; Rheumatoide Arthritis ; Basistherapie ; Langzeitverlauf
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Ziel der Arbeit: Untersuchung der Langzeiteffektivität und Verträglichkeit der Basistherapie mit Methotrexat (MTX), Azathioprin (AZA), intramuskulärem Gold, D-Penicillamin (DPA), Sulfasalazin (SASP) und Cholorochin (CQ) bei rheumatoider Arthritis (RA). Methoden: Zwischen 1979 und 1994 wurden Daten von 1681 Patienten des Rheumazentrums Rostock prospektiv erfaßt. Eine 50%ige Reduktion der Anzahl geschwollener Gelenke war erforderlich, um die Therapie fortzuführen. Zusätzlich wurden in halbjährlichen Abständen ein modifizierter Lansbury-Index, der Bewegungsfunktionstest nach KEITEL sowie akute-Phase-Parameter erfaßt. Nebenwirkungen, die zum Abbruch der Therapie führten, wurden ebenfalls festgehalten. Ergebnisse: Nach einer Beobachtungszeit von mindestents vier Jahren nahmen noch 39,6% bzw. 28,3% der Patienten MTX bzw. AZA ein. 18,2% bekamen Gold, 16,9% DPA. SASP und CQ wurden von 13,5 bzw. 6,6% der Patienten eingenommen. Die Abbruchraten wegen Nebenwirkungen (NW) betrugen für MTX, AZA and SASP 15,9%, 15,3% bzw. 17,7%, während 34,8% CQ wegen NW absetzten (Gold: 27,4%, DPA: 26,9%). Die Mehrzahl der Therapieabbrüche erfolgte bereits im ersten Jahr der Behandlung. Subgruppen seropositiver Patienten bzw. Patienten mit Rheumaknoten oder erosiven Verläufen hatten ein schlechteres Ansprechen auf die Behandlung, unabhängig von der Art des eingesetzten Basistherapeutikums. Schlußfolgerung: MTX war in der Langzeittherapie die effizienteste Substanz, gefolgt von AZA, während CQ die geringste Rate von Langzeitanwendern aufwies. Die Ergebnisse unterstreichen den Stellenwert von Langzeitbeobachtungen unter klinischen Alltagsbedingungen in Ergänzung zu kontrollierten klinischen Studien.
    Notes: Summary Objective: To study the long-term efficacy and safety of methotrexate (MTX), intramuscular gold, azathioprine (AZA), chloroquine (CQ), sulphasalazine (SASP), and D-penicillamine (DPA) in rheumatoid arthritis (RA) patients. Methods: Between 1979 and 1994, clinical data were prospectively gathered in a single center. 1681 patients were followed-up for at least 4 years. A 50% reduction of the swollen joint count was required to continue therapy. In addition, a modified Lansbury index, the Keitel function test, and laboratory parameters were determined every six months. Side effects leading to the discontinuation of treatment were recorded as well. Results: After an observation period of more than four years, 39.6% and 28.3% of patients were taking MTX and AZA, respectively; 18.2% were receiving gold, 16.9% remained on DPA. SASP and CQ were still applied in 13.5% and 6.6%. MTX, AZA and SASP had a drop-out rate due to toxicity of 15.9%, 15.3% and 17.7%, whereas 34.8% had to discontinue CQ (gold: 27.4%, DPA: 26.9%). The majority of dropouts occurred within the first year of treatment. Subgroups of seropositive patients and patients with rheumatoid nodules had a poorer treatment efficacy irrespective of the DMARD. Conclusion: In the long-term application, MTX was the most efficient compound, followed by AZA, whereas CQ had the poorest drug survival. Our results underline the value of long-term observations under the conditions of clinical practice as a supplement to controlled clinical trials.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003930050181
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    Electronic Resource
    Chronische Krankheitsbilder am Sprunggelenk (1999)
    Springer
    Der Radiologe 39 (1999), S. 52-59 
    Details
    ISSN: 1432-2102
    Keywords: Schlüsselwörter ; Key words
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The etiology of chronic diseases of the ankle joint comprises a wide spectrum including chronic inflammatory processes and chronic degenerative, tumorous and neuropathic processes, as well as some specific syndromes based on chronic changes of the ankle joint. Of the inflammatory processes, chronic juvenile arthritis (JVC) is the most common disease. However, also Reiter disease, psoriasis or chronic monoarthritid diseases such as gout, as well as granulomatous diseases (tuberculosis, sarcoidosis) and fungal infections, may affect the ankle joint in a chronic course. Chronic degenerative changes are usually secondary due to abnormal positioning of the joint constituents or repetitive trauma. Neuropathic changes, as frequently seen in the course of diabetes, present with massive osseous destruction and malposition of the articular constituents. Chronic osseous as well as cartilaginous and synovial changes are seen in hemophilic patients. Chronic traumatic changes are represented by pigmented villonodular synovitis (PVNS), and chondromatosis, both with a predilection for the ankle joint. Due to the possibilities of magnetic resonance imaging (MRI), diagnosis of chronic ankle changes includes chronic ligamentous, tendinous and soft tissue changes. With the use of MRI, specific syndromes can be defined which particularly affect the ankle joint in a chronic way, such as the os trigonum syndrome, the anterolateral impingement syndrome and the sinus tarsi syndrome. Nevertheless, plain film radiographs are still the basic element of any investigation. MRI, however, can be potentially used as a second investigation, saving an unnecessary cascade of investigations with ultrasound and CT. The latter investigations are used only with very specific indications, for instance CT for subtle bone structures and sonography for a limited investigation of tendons or evaluation of fluid. Particularly due to the possibilities of MRI and the development of special gradient-echo imaging or high-resolution coils, the investigation of the ankle joint still offers a wide spectrum of innovation for the next years, which is particularly enforced by the increasing demand for specific diagnosis of chronic diseases in orthopedic medicine.
    Notes: Zusammenfassung Die Ätiologie chronischer Krankheitsbilder am Sprunggelenk ist vielfältig. Chronisch entzündliche Veränderungen, wie sie im Rahmen einer chronisch juvenilen Arthritis, des M. Reiter, der Psoriasis oder chronischer Monoarthritiden, wie der chronischen Gicht zu beobachten sind, haben nicht selten ihre Manifestation am Sprunggelenk. Seltenere entzündlich chronische Affektionen hingegen können jedoch auch bei enteropathischen Arthritiden, granulomatösen Erkrankungen, wie der Tuberkulose oder Sarkoidose, beobachtet werden. Auch chronisch verlaufende Pilzaffektionen können zu atypischen Bildern führen. Chronisch degenerative Erkrankungen entstehen am Sprunggelenk fast ausschließlich sekundär. Prädisponierend sind hier angeborene oder erworbene Fehlhaltungen sowie chronische Veränderungen auf Basis abgelaufener oder repetitiver Traumen. Der neuropathische Formenkreis stellt eine weitere Causa chronischer Veränderungen dar, mit im fortgeschrittenem Stadium massiven Gelenks- und ossären Veränderungen. Chronische Veränderungen sind auch bei der Hämophilie im Rahmen des Blutergelenkes zu erwarten. Als chronisch tumoröse Veränderungen können die pigmentierte villonoduläre Synovitis (PVNS) und die Gelenkschondromatose betrachtet werden, mit teils ossären und teils charakteristischen Kapsel und Weichteilveränderungen. Die modernen Gelenkdiagnostik umfaßt zudem auch chronische Veränderungen an den Sehnen und Bändern. Besondere diagnostische Herausforderungen stellen letzendlich Syndrome dar, die klinisch zwar beobachtet, jedoch erst durch moderne Bildgebung in den letzten Jahren zunehmend spezifiziert werden konnten. Diese umfassen zum Beispiel das „Os-trigonum-Syndrom”, das „anterolaterale Weichteilimpingement” und das „Sinus-tarsi-Syndrom”. Wie in der allgemeinen Gelenkdiagnostik ist auch weiterhin das Nativbild als Basisuntersuchung unerläßlich. Der Einsatz der Magnetresonanztomographie (MRT) als Zweituntersuchung erspart oft eine kostenintensive und belastende Untersuchungskaskade. Der Einsatz moderner Sequenzen oder gezielte Kontrastmittelgabe erlauben zunehmend spezifische Diagnosen. Der Einsatz der Sonographie und ebenso der CT muß gezielt durchgeführt werden. Die Vielfalt der möglichen chronisch pathologischen Veränderungen und dem gegenüberstehend die Vielfalt der Untersuchungsmethoden, im speziellen der MRT-Techniken, zusammen mit den komplexen anatomischen Verhältnissen am Sprunggelenk stellen eine besondere Herausforderung an den Radiologen dar.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001170050477
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    Electronic Resource
    Breast cancer screening by mammography in Norway. Is it cost- effective? (1999)
    Springer
    Annals of oncology 10 (1999), S. 197-203 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; cost-effectiveness ; mammography ; screening
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Mammography screening is a promising method for improving prognosis in breast cancer. Patients and methods: In this economic analysis, data from the Norwegian Mammography Project (NMP), the National Health Administration (NMA) and the Norwegian Medical Association (NMA) were employed in a model for cost-effectiveness analysis. According to the annual report of the NMP for 1996, 60,147 women aged 50–69 years had been invited to a two-yearly mammographic screening programme. 46,329 (77%) had been screened and 337 (0.7%) breast cancers had been revealed. The use of breast conserving surgery (BCS) was in this study estimated raised by 17% due to screening, the breast cancer mortality decreased by 30% and the number of life years saved per prevented breast cancer death was calculated 15 years. Results: The cost per woman screened was calculated £75.4, the cost per cancer detected £10,365 and the cost per life year (LY) saved £8,561. A raised frequency of BCS, diagnosis and adjuvant chemotherapy brought two years forward, follow-up costs and costs/savings due to prevented breast cancer deaths were all included in the analysis. A sensitivity analysis documented mammography screening cost-effective in Norway when four to nine years are gained per prevented breast cancer death. Conclusion: Mammography screening in Norway looks cost- effective. Time has come to encourage national screening programmes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008376608270
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    The third-generation non-steroidal aromatase inhibitors: A review of their clinical benefits in the second-line hormonal treatment of advanced breast cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 377-384 
    Details
    ISSN: 1569-8041
    Keywords: anastrozole ; aromatase inhibitors ; breast cancer ; hormonal therapy ; letrozole ; review ; vorozole
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Three new aromatase inhibitors have recently completed phase III evaluation as treatment of metastatic breast cancer in post-menopausal women whose disease has progressed despite tamoxifen therapy: anastrozole (ARIMIDEX, Zeneca), letrozole (FEMARA, Novartis) and vorozole (RIVIZOR, Janssen). All belong to the third generation of non-steroidal aromatase inhibitors, and each is superior to previous generations in terms of potency and selectivity. The trials that have been performed compare each agent to megestrol acetate, and letrozole and vorozole to aminoglutethimide. Although the studies are not directly comparable due to differing study designs and patient populations, it has been demonstrated each of these drugs provides single agent, once-daily, oral palliation of hormone-responsive, post-menopausal metastatic breast cancer. Letrozole is clearly more effective than megestrol acetate, and anastrozole and vorozole are possibly so. All three are better tolerated than the progestin, particularly in terms of weight gain. Both letrozole and vorozole are significantly more effective, and better tolerated than aminoglutethimide. Overall, this most recent generation of aromatase inhibitors is a clear improvement on our current standard second-line therapies. In 1999, tamoxifen remains the first choice in the hormonal therapy of breast cancer. Following tamoxifen failure, the optimal second-line hormonal therapy remains undefined, but aminoglutethimide and megestrol acetate are no longer optimal therapy in this setting. The third-generation non-steroidal aromatase inhibitors must now be compared to each other, to the steroidal aromatase inhibitors, to the pure anti-oestrogens, and to tamoxifen.
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    URL: http://dx.doi.org/10.1023/A:1008368300827
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    Synchronous inflammatory breast cancer and advanced ovarian carcinoma: A case with prolonged disease-free survival (1999)
    Springer
    Annals of oncology 10 (1999), S. 585-588 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; cisplatin ; ovarian cancer ; paclitaxel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Despite the known association of these malignancies, the incidence of a synchronous presentation of breast and ovarian cancer is low, and the current literature does not address an approach to this clinical problem directly. We report a greater than 2.5 year disease-free survival in a patient treated for synchronous stage IIIB inflammatory breast cancer and stage IIIC epithelial ovarian cancer. The prolonged disease-free survival in our case may provide some guidance in this unusual clinical situation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008239124657
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  • 36
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    Autologous stem-cell transplant after conventional dose adjuvant chemotherapy for high-risk breast cancer: Impact on the delivery of local-regional radiation therapy (1999)
    Springer
    Annals of oncology 10 (1999), S. 929-936 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; local regional therapy ; stem-cell transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: High-dose chemotherapy with autologous stem-cell transplantation is used increasingly in the treatment of poor-prognosis primary breast cancer. Because these patients may be cured with standard multimodality therapy, it is important to address both the efficacy of transplantation, and its effect on the delivery of standard treatments including local radiation therapy. Patients and methods: Patients with high risk primary breast cancer were treated with high-dose cyclophosphamide and thiotepa and stem-cell transplant following surgery and conventional-dose adjuvant chemotherapy. Outcome, including sites of failure and delivery of local radiation therapy, was assessed for 103 patients. Results: Overall and disease-free survival rates at 18 months were 83% (± 4%) and 77% (± 4%) respectively. Twenty patients (19.4%) received radiation therapy prior to transplant. Of the remaining 83, 77 received radiation therapy after transplant. Overall, 5 (19.2%) of 26 first sites of recurrence were local alone. For patients receiving radiation prior to transplant, 3 of 7 (43%, 95% CI: 6%–80%) sites of first recurrence were local, while 2 of 19 (10.5%, 95% CI: 0%–24.5%) sites of first recurrence were local alone in patients receiving post-transplant radiation or no radiation. Conclusion: Transplantation does not appear to significantly compromise the delivery or outcome of local radiation therapy for primary breast cancer.
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    URL: http://dx.doi.org/10.1023/A:1008393204854
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    Electronic Resource
    Adjuvant Therapy of Breast Cancer: Update (1999)
    Springer
    Annals of oncology 10 (1999), S. 129-137 
    Details
    ISSN: 1569-8041
    Keywords: adjuvant treatment ; breast cancer ; systemic therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The theoretical prediction that breast cancer is a systemic disease, and that patients may benefit from addition of systemic therapy to local treatment, has now been confirmed by three decades of clinical investigations. A long-term follow up of individual trials and the International Overview based on meta-analyses clearly showed the potential of both hormonal therapies and chemotherapy to prolong disease-free and overall survival in nearly all groups of patients. The benefits have been demonstrated for both premenopausal and postmenopausal patients, with both node-negative and node-positive disease. However, there is still considerable uncertainty regarding the most appropriate treatment for each individual patient. In the present review, the results of meta-analysis are highlighted in the context of the new trials supporting the value of chemoendocrine therapy and anthracycline-based therapy. The results of prospective randomised trials evaluating the role of dose intensification, drug sequencing and dose density are discussed. Also presented are new treatment strategies, such as preoperative chemotherapy and high-dose chemotherapy with stem cell support, the value of which remains to be confirmed. Future possibilities opened by inclusion of biologics into adjuvant therapy are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008362521127
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  • 38
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    Electronic Resource
    New Developments in Chemotherapy of Advanced Breast Cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 139-146 
    Details
    ISSN: 1569-8041
    Keywords: anthracycline ; breast cancer ; chemotherapy ; HER-2 antibody ; N,N-diethyl-2[4-(phenylmethyl)-phenoxy] ethanamine.HCl (DPPE, BMS-217380-01) ; paclitaxel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Anthracyclines and taxanes are the two most active classes of chemotherapy for the treatment of advanced breast cancer. Recent studies have investigated combination therapy including doxorubicin (Dox) and paclitaxel. The efficacy of this combination has been established in a phase III study conducted by ECOG, comparing Dox/paclitaxel versus Dox versus paclitaxel. The combination is superior to Dox or paclitaxel with respect to response rate and time to disease progression, indicating that the combination provides a new standard for the first line treatment of metastatic breast cancer [1]. Phase II studies using higher doses of Dox and using shorter infusions of paclitaxel have suggested the combination can be further optimised; Gianni reported a 94% objective response rate using Dox 60 mg/m2 followed by paclitaxel 175 mg/m2 given over three hours [2]. The more active regimens are associated with enhanced cardiotoxicity; this toxicity can be avoided, however, by limiting the exposure to doxorubicin. The newer regimens have now been moved into phase III studies. Future progress for this disease will depend on the introduction of new agents. Two novel drugs are currently being investigated in randomised phase III trials as potentiators of Dox and/or paclitaxel. One is a monoclonal antibody from Genentech (Herceptin, trastuzumab) directed at the HER-2/neu oncogene, which is overexpressed in 〉25% of breast cancers [3]. Recent results indicate that Herceptin in combination with paclitaxel (or with a Dox plus cyclophosphamide regimen) induces a higher response rate (RR) and prolongs the time to disease progression when compared to chemotherapy alone. The second agent N,N-diethyl-2[4-(phenylmethyl)-phenoxyl] ethanamine.HCl (DPPE, BMS-217380-01), when combined with Dox, was associated with a higher RR than previously observed with Dox alone [4]. A randomised trial of Dox versus Dox plus DPPE is ongoing. The possible mechanisms underlying chemo-potentiation by these agents are discussed. As new anthracycline/taxane combinations establish themselves in earlier stages of the disease, the need for effective, non-cross resistant salvage regimens will emerge.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008318725670
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  • 39
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    Electronic Resource
    Cowden disease and Lhermitte Duclos disease, markers of breast carcinoma: Report of two patients (1999)
    Springer
    Annals of oncology 10 (1999), S. 1241-1243 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; Cowden disease ; Lhermitte Duclos
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008317923860
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  • 40
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    Electronic Resource
    A randomized, open, parallel-group trial to compare the endocrine effects of oral anastrozole (Arimidex®) with intramuscular formestane in postmenopausal women with advanced breast cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 1219-1225 
    Details
    ISSN: 1569-8041
    Keywords: anastrozole ; Arimidex® ; aromatase inhibitor ; breast cancer ; formestane ; oestradiol ; tolerability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: This study provides a direct randomized comparison of a new-generation, non-steroidal aromatase inhibitor, anastrozole (Arimidex®), with a steroidal aromatase inhibitor (formestane) with respect to oestrogen (oestradiol, oestrone, and oestrone sulphate) suppression and tolerability. Patients and methods: Sixty postmenopausal women with advanced breast cancer were randomized to receive either anastrozole 1 mg once daily orally (n = 29), or formestane 250 mg once every two weeks by intramuscular injection (n = 31). Treatment was continued until progression of disease or withdrawal from the study. The primary endpoints of this study were oestradiol suppression and tolerability. The secondary endpoints included oestrone and oestrone sulphate suppression. All laboratory analyses were conducted ‘blind’ of the randomized drug treatment. Results: Anastrozole produced a greater and more consistent suppression of oestradiol levels compared with formestane. Based on two- and four-week measurements, the mean fall from baseline (pre-dose) in oestradiol level was 79% and 58% in the anastrozole and formestane groups, respectively (P = 0.0001). After four weeks of treatment, oestrone and oestrone sulphate levels were also suppressed to a greater extent by anastrozole compared with formestane (oestrone: 85% versus67%, respectively, P = 0.0043; oestrone sulphate: 92% versus 67%, respectively, P = 0.0007). No statistical differences were seen between the two drugs in the incidence of adverse events. Conclusions: Anastrozole provides a more consistent and significantly more effective suppression of oestradiol compared with formestane. Similar results were observed for oestrone and oestrone sulphate. The clinical significance of these differences in total oestrogen suppression remains to be established.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008308609325
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  • 41
    Electronic Resource
    Electronic Resource
    Screening Mammography for Early Detection of Breast Cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 121-127 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; mammography ; prevention ; screening
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract From numerous studies on breast cancer it can be concluded that no single measure can lessen the burden of this frequent cancer in women in all developed countries. Complex strategies including primary prevention by identification of risk factors and their modification, secondary prevention by earlier detection and tertiary prevention by improving treatment outcome are needed to control the disease. Besides age, the established breast cancer risk factors include certain benign breast diseases, family history, ionising radiation, some reproductive factors and obesity. Primary prevention includes general recommendation for healthy lifestyle, e.g., avoidance of obesity, proper diet, physical activity and moderate alcohol consumption. Randomised controlled trials conducted in the USA, Canada, Scotland and Sweden have shown that regular mammography, alone or in combination with clinical examination, is effective in reducing mortality for about 30% in women over the age of 50, and much less in younger population. However, mammography screening has several drawbacks, the major being its tendency towards false positive and false negative results with all their potential psychosocial consequences. High quality assurance and control, as well as effective and readily available treatment, all of which demand high investments, are indispensable for good results. Even in the absence of organised screening, the availability of effective treatment may contribute to reduction in breast cancer mortality.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008310503380
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  • 42
    Electronic Resource
    Electronic Resource
    Cytomegalovirus pneumonia in a patient with breast cancer on chemotherapy: Case report and review of the literature (1999)
    Springer
    Annals of oncology 10 (1999), S. 461-465 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; cytomegalovirus pneumonia ; dexamethasone ; ganciclovir ; standard dose chemotherapy regimen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cytomegalovirus (CMV) pneumonia in the setting of non-transplantation patients is a rarity. We present a case of CMV pneumonitis in a woman with stage IV breast cancer, with brain metastases, receiving both chemotherapy and systemic corticosteroids. A review of the literature reveals this as a unique case. Potential viral etiologies should therefore be considered in cancer patients with pneumonia receiving non-transplantation chemotherapy-regimens, particularly if steroids are a component of their therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008360927507
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  • 43
    Electronic Resource
    Electronic Resource
    Front-line treatment of metastatic breast cancer with docetaxel and epirubicin: A multicenter dose-escalation study (1999)
    Springer
    Annals of oncology 10 (1999), S. 547-552 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; docetaxel ; epirubicin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To determine the maximum tolerable dose (MTD) and the dose-limiting toxicity (DLT) of docetaxel (D) in combination with epirubicin (Epi) in patients with advanced breast cancer. Patients and methods: Forty-seven chemotherapy-naïve metastatic breast cancer patients aged 〈75 years with PS (WHO) 0–2 and adequate bone marrow, renal, liver and cardiac function, were enrolled in the study. Epi was given as a five-min bolus i.v. infusion on day 1 (d1) in escalated doses with increments of 10 mg/m2; D was given in a one-hour infusion after appropriate premedication on either day 1 or on day 2 in escalated doses with increments of 10 mg/m2. The patients' median age was 60 years, 42 (89%) had a PS (WHO) 0–1, 16 (34%) were premenopausal and 25 (53%) had visceral disease. Results: When the two drugs were given on the same day, the MTD1 was reached at the doses of Epi 60 mg/m2 and D 80 mg/m2; administration of G-CSF could not result in a dose intensification. When the drugs were given on two consecutive days, the MTD2 was reached at the doses of Epi 80 mg/m2 (d1) and D 90 mg/m2 (d2). The dose-limiting events were febrile neutropenia and grade 4 neutropenia, which developed in 30 (64%) patients during the study; among 227 delivered cycles grade 3–4 neutropenia occurred in 64 (28%) cycles but only 22 (10%) of them were complicated by fever. There were no septic deaths. Grade 1–2 neurosensory toxicity occurred in nine (19%) patients, mild edema in eight (17%) and allergic reactions in five (11%). Four (9%) patients presented a greater than 10% decrease of LVEF and treatment discontinuation was required in two of them; none of the patients developed congestive heart failure. Nevertheless, one patient suddenly died 10 days after treatment initiation of myocardial ischemia, and this death is considered treatment-related. Five (14.7%) complete and thirteen (38.2%) partial responses (ORR: 53.9%; 95% confidence interval: 36.1%–69.7%) were observed in 34 evaluable patients. Ten (29.4%) and six (17.6%) patients had stable and progressive disease, respectively. The median duration of response and time to tumor progression were five and seven months, respectively. The median survival has not yet been reached. Conclusions: The combination of epirubicin and docetaxel is a feasible and well tolerated regimen, but the MTD depends on the administration schedule of the drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026441804889
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  • 44
    Electronic Resource
    Electronic Resource
    Depression in breast cancer patients: The need for treatment (1999)
    Springer
    Annals of oncology 10 (1999), S. 627-636 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; depression ; diagnosis ; treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008328005050
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  • 45
    Electronic Resource
    Electronic Resource
    A phase I study of sequential vinorelbine followed by paclitaxel (1999)
    Springer
    Annals of oncology 10 (1999), S. 861-863 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; paclitaxel ; phase I ; vinorelbine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: In vitro experiments suggest that administration of vinorelbine preceding paclitaxel results in synergistic cytotoxic effects. A phase I dose escalation trial of vinorelbine daily × 3 with paclitaxel on day 3 repeated every 28 days in metastatic breast cancer patients was completed. Patients and methods: Female patients, PS 0–2, without evidence of CNS disease or prior neuropathies were treated with vinorelbine at dose levels 7, 10, 13 mg/m2 per day and paclitaxel over three hours at dose levels of 135, 175, and 200 mg/m2. Results: Twenty-eight patients with six dose levels were studied. At dose level 1, patients developed intolerable but reversible neutropenia. Subsequent dose levels required filgrastim. Dose limiting toxicities were myalgia and fatigue at vinorelbine 13 mg/m2 /day and paclitaxel 200 mg/m2. Neuropathy was minor. Twelve of twenty-five patients with measurable disease had a rapid response which did not correlate with dose level. Conclusions: Sequential administration of these two agents demonstrates activity in breast cancer patients. Phase II dosing on this schedule should be vinorelbine 13 mg/m2/day × 3 and paclitaxel 175 mg/m2. With proper selection of patients, concern about neurologic toxicity should not impede future trials of vinorelbine with paclitaxel.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008351915582
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  • 46
    Electronic Resource
    Electronic Resource
    Ala99ser mutation in RIα Regulatory Subunit of protein kinase A causes reduced kinase activation by cAMP and arrest of hormone-dependent breast cancer cell growth (1999)
    Springer
    Molecular and cellular biochemistry 195 (1999), S. 77-86 
    Details
    ISSN: 1573-4919
    Keywords: protein kinase A ; site-directed mutagenesis ; breast cancer ; growth arrest ; cAMP response element
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Expression of the RIα regulatory subunit of protein kinase A type I is increased in human cancer cell lines, in primary tumors, in cells after transformation, and in cells upon stimulation of growth. Ala99 (the pseudophosphorylation site) of human RIα was replaced with Ser (RIα-p) for the structure-function analysis of RIα. MCF-7 hormone- dependent breast cancer cells were transfected with an expression vector for the wild-type RIα or mutant RIα-p. Overexpression of RIα-P resulted in suppression of protein kinase A type II, the isozyme of type I kinase, production of kinase exhibiting reduced cAMP activation, and inhibition of cell growth showing an increase in G0/G1 phase of the cell cycle and apoptosis. The wild-type RIα overexpression had no effect on protein kinase A isozyme distribution or cell growth. Overexpression of protein kinase A type II regulatory subunit, RIIβ, suppressed RIα and protein kinase A type I and inhibited cell growth. These results show that the growth of hormone-dependent breast cancer cells is dependent on the functional protein kinase A type I.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006934113439
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  • 47
    Electronic Resource
    Electronic Resource
    Agonist and antagonist-induced qualitative and quantitative alterations of progesterone receptor from breast cancer cells (1999)
    Springer
    Molecular and cellular biochemistry 199 (1999), S. 49-56 
    Details
    ISSN: 1573-4919
    Keywords: progesterone receptor ; breast cancer ; steroid receptor agonists ; antagonists ; T47D cells ; RU486
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract T47D cells, cultured in medium containing serum stripped of endogenous steroids, proliferate in response to treatment with the progesterone receptor (PR) agonist, R5020 or the PR agonist/antagonist, RU486, whereas the full PR antagonist, ZK98299 has no proliferative effects. Under estrogenized conditions, all of the PR ligands tested inhibit cell growth [23]. In order to determine whether the levels or phosphorylation state of PR are reflected in the growth patterns of T47D cells, we monitored the effects of these PR ligands on the immunoblotted PR band intensities, the relative intensities, of PR-A and PR-B, and their phosphorylation states that are reflected in their altered mobility during SDS-PAGE. Under conditions where the PR ligands inhibit cell proliferation, each ligand had distinctively different qualitative and quantitative effects on PR. Short term treatment of the cells with R5020 or RU486 induced a characteristic phosphorylation-dependent upshift of both PR-A and PR-B. The phosphorylated PR was stable for up to 4 days after treatment of the cells with RU486, but was down regulated between 6-24 h after treatment with R5020. No replenishment of PR in cells treated with R5020 was detected. ZK98299, at concentrations tested, had no qualitative or quantitative effects on PR. Culturing cells for 8 days in medium containing steroid-depleted serum caused a significant reduction in the PR band intensity without causing a change in the ratio of PR-A and PR-B or their phosphorylation states. This decrease in the PR band intensity was reversed by maintaining the cells in 1 nM estrogen, but was potentiated by RU486 or ZK98299. These observations support the view that decreased PR levels may play a role in the stimulatory effects of R5020 and RU486 when cells are cultured under non-estrogenized conditions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006982528297
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  • 48
    Electronic Resource
    Electronic Resource
    Effects of antiprogestins on the rate of proliferation of breast cancer cells (1999)
    Springer
    Molecular and cellular biochemistry 198 (1999), S. 141-149 
    Details
    ISSN: 1573-4919
    Keywords: T47D cells ; breast cancer ; cellular proliferation ; progesterone ; estradiol ; steroid receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract We have examined the influence of progestins (progesterone, R5020) and antiprogestins (RU486, ZK98299, Org 31710 and Org 31806) on the rate of proliferation of wild type T47D cells cultured in whole fetal bovine serum (FBS) or in single charcoal stripped fetal bovine serum (SSFBS). All of the progesterone antagonists RU486, ZK98299 and two novel antiprogestins Org 31710 and Org 31806 inhibited cell proliferation when cells were cultured in FBS. In contrast, all of the antiprogestins with the exception of ZK98299 enhanced cell growth when cells were cultured in SSFBS. This stimulatory effect of RU486 was observed only at a high concentration of the ligand (1 μM). The effect of R5020, however, was concentration independent. The number of cells in the presence of RU486 was ~ 600% followed by R5020 ~ 400% above control values after a 28 day culturing period. In contrast, when the cells were grown in the presence of medium containing non-stripped whole serum, RU486 inhibited the extent of cell proliferation by 45%. Estradiol (E2) stimulated the rate of proliferation in cells cultured in SSFBS. Similar to when cells were cultured in whole serum, the antiprogestins inhibited cell growth in E2-supplemented SSFBS. Detection of the growth enhancement effects of progesterone receptor (PR) ligands such as RU486 and R5020 on the cells grown in charcoal-stripped medium appear to require the removal of E2 by charcoal stripping of the serum.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006945813508
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  • 49
    Electronic Resource
    Electronic Resource
    Toward Checkmate: Biology and Breast Cancer Therapy for the New Millennium (1999)
    Springer
    Investigational new drugs 17 (1999), S. 417-427 
    Details
    ISSN: 1573-0646
    Keywords: breast cancer ; growth factors ; metalloproteinase ; angiogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract A better understanding of the biology of breast cancer should leadto the rational development of new treatments and the ability tocustomize therapy for individual patients. Though promising intheory, translating advances in biological knowledge to the clinichas been difficult. Recently several areas of research haveproduced treatments which have entered clinical trials; three willbe reviewed here. The growth of breast cancer is regulated bygrowth factors and their receptors; amplification or overexpressionis associated with poor prognosis. As such inhibition of growthfactors and/or growth factor receptors may provide an idealtherapeutic target. Herceptin binds to c-erbB-2, a member of theepidermal growth factor receptor family. Significant responses wereseen in patients with c-erbB-2 overexpressing breast cancer withHerceptin administered as a single agent or in combination withchemotherapy. Herceptin was approved by the Food and DrugAdministration in late 1998. Breast cancer invasion and metastasisrequires degradation of the surrounding basement membrane by matrixmetalloproteinases and other proteolytic enzymes. Syntheticinhibitors of these enzymes are now in clinical trials. Breastcancers must stimulate angiogenesis, the growth of new bloodvessels, in order to grow beyond a few millimeters in diameter.This nascent vascular network provides another opportunity fortherapy. Preclinical models support the critical role ofangiogenesis and the therapeutic benefit of angiogenesisinhibition; clinical trials are underway.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006311227965
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  • 50
    Electronic Resource
    Electronic Resource
    Evaluation of seprase activity (1999)
    Springer
    Clinical & experimental metastasis 17 (1999), S. 67-72 
    Details
    ISSN: 1573-7276
    Keywords: breast cancer ; extracellular matrix ; gelatinase ; invasion ; matrix metalloproteinase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Seprase is a serine protease that is integral to the plasma membrane and is overexpressed by invasive tumor cells (Piñeiro-Sánchez et al., J Biol Chem 1997; 272: 7595–601; Monsky et al., Cancer Res 1994; 54: 5702–10). Seprase activity is most often assessed by zymography, which is not a quantitative assay. This study establishes a relatively simple and quantitative method for determining seprase activity. The degradation of a 3H-gelatin substrate is measured in the presence of 5 mM EDTA which inhibits matrix metalloproteinases but not seprase. The quantitative character of the assay was demonstrated using partially purified seprase from chicken embryos, a preparation that lacks detectable matrix metalloproteinase activity. In this assay, release of 3H-gelatin fragments is linear over time for 1.5 μg/assay seprase concentration as well as for preparations concentrated or diluted by five fold (7.5 μg/assay and 0.3 μg/assay respectively). Additional experiments were performed to validate the quantification of seprase activity using the radiographic assay by comparing the results to zymography. Exposure to 22 or 37 °C results in maximal seprase activity while exposure to 80 or 100 °C completely abolishes seprase activity in both zymography and the radiographic assay. Exposure to 60 °C abolished seprase activity as judged by zymography, but about 50% gelatinase activity was observed using the 3H-gelatin substrate. Immunopreciptiation with seprase-specific antibody specifically removed seprase and lowered the seprase activity remaining in the extracts as judged by both assays. Investigation of the seprase that was partially purified from human breast cancer tissue revealed that its specific activity (cpm gelatin fragments released/ {mg protein×h}) is five times greater than that of seprase purified from chicken embryos. This assay will be useful for determining the seprase activity in extracts of tumor tissues and cells as well as for identifying inhibitors of seprase.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026430206274
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  • 51
    Electronic Resource
    Electronic Resource
    Loss of heterozygosity in BRCA1 and BRCA2 markers and high‐grade malignancy in breast cancer (1999)
    Springer
    Breast cancer research and treatment 53 (1999), S. 9-17 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; microsatellites ; prognostic factors ; 17q21 region ; 13q12‐13 region
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Loss of heterozygosity (LOH) in loci of the 17q21 and 13q12‐13 regions can collaborate in the inactivation of BRCA1, BRCA2, and possibly other genes implicated in the pathogenesis of breast carcinomas. We investigate allelic losses in microsatellites of the BRCA1 and BRCA2 regions, and their correlations with seven pathologic parameters in 140 breast carcinomas. Those cases showing LOH in the region of the RB gene, 13q14, were excluded from the study. The LOH analysis was performed by amplifying DNA by PCR, using four markers of the 17q21 region (D17S856, D17S855, D17S1323, and D17S1327) and four markers of the 13q12‐13 region (D13S290, D13S260, D13S310, and D13S267). LOH in the BRCA1 region was found in 47% of tumors, correlating significantly with estrogen receptor content (p = 0.025), progesterone receptors (p = 0.004), higher grade (p = 0.0008), peritumoral vessel invasion (p = 0.001), and lymph node metastases (p = 0.002). When we excluded the cases with LOH in the BRCA2 region and those not informative for it, the significance disappeared. In the BRCA2 region, a rate of LOH of 51% was found; it correlated significantly with estrogen receptor content (p = 0.002), progesterone receptors (p =0.03), peritumoral vessel invasion (p = 0.005), higher grade (p =0.002), and lymph node metastases (p = 0.001). When cases with BRCA1 losses and those not informative were excluded, again the significance disappeared. Concomitant losses in the BRCA1 and BRCA2 regions were found in 32% of cases, correlating significantly with lymph node metastases (p = 0.0002), estrogen receptor content (p = 0.003), progesterone receptors (p = 0.001), histologic grade (p =0.01), and peritumoral vessel invasion (p = 0.0004). These results suggest that concomitant losses in both regions could have a functional effect, influencing the presence of a poor tumor pathophenotype in breast carcinomas.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006082117266
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  • 52
    Electronic Resource
    Electronic Resource
    Quantitative changes in cytological molecular markers during primary medical treatment of breast cancer: A pilot study (1999)
    Springer
    Breast cancer research and treatment 53 (1999), S. 51-59 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; neoadjuvant therapy ; FNA ; estrogen receptor ; progesterone receptor ; p53 ; Bcl‐2 ; Ki67 ; SPF ; ploidy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aim: To quantify the changes in biological molecular markers during primary medical treatment in patients with operable breast cancer and to assess their possible relationship with response to treatment. Methods: The treatment group consisted of 31 patients with operable breast carcinomas, median age 57 years (range 41–67), treated with four 3‐weekly cycles of chemotherapy with Mitoxantrone, methotrexate (± mitomycin C), and tamoxifen before surgery. Fine needle aspiration (FNA) was used to obtain samples from patients prior to and at 10 or 21 days post‐treatment. The following molecular markers were assessed: estrogen receptor (ER), progesterone receptor (PgR), p53, Bcl‐2, and Ki67 measured by immunocytochemistry, and ploidy and S‐phase fraction (SPF) by flow cytometry. To evaluate the reproducibility of the technique, repeat FNA was performed in a separate non‐treatment control group of 20 patients and the same molecular markers assessed, two weeks after the first sample with no intervening treatment. Results: The non‐treatment control group showed a high reproducibility for the measurement of molecular markers from repeat FNA. In the treatment group there was a non‐significant reduction in SPF and a significant reduction (p = 0.005) in Ki67. Patients who responded to neoadjuvant therapy were more likely to have a reduction in these two markers than those who failed to respond. Similarly, a reduction in ER scores was observed between the first and second samples (p = 0.04). For PgR, the change between the first and second samples was not significant although there was a significant difference between responders and non‐responders (p = 0.03). All nine patients with an increase in PgR were responders. No significant changes in p53 or Bcl‐2 were observed during treatment. Conclusion: Molecular markers can be adequately measured from FNA samples prior to and during neoadjuvant therapy. Changes in cellular proliferation and hormone receptors have been shown that may be related to tumour response. These relationships should be assessed in a larger cohort of patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006179511178
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  • 53
    Electronic Resource
    Electronic Resource
    Human papillomavirus 16 in breast cancer of women treated for high grade cervical intraepithelial neoplasia (CIN III). (1999)
    Springer
    Breast cancer research and treatment 53 (1999), S. 121-135 
    Details
    ISSN: 1573-7217
    Keywords: HPV 16 ; breast cancer ; CIN III ; PCR ; southern blot ; in situ hybridization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Women with both a history of high grade cervical intraepithelial neoplasia (CIN III) and breast carcinoma as second primary cancer were selected for studying the presence of HPV in breast carcinomas. Paraffin embedded material from 38 patients with 41 breast carcinoma cases after CIN III were examined by polymerase chain reaction (PCR) and in situ hybridization. By PCR we detected HPV 16 DNA in 19 out of 41 cases (46%) of the breast carcinomas. One case proved to be HPV 16 positive also by in situ hybridization. HPV 16 was also detected in 32 out of the 38 patients with CIN III (84%). All HPV 16 positive breast carcinomas were HPV 16 positive in their corresponding CIN III lesions. Eight patients with diagnosed breast cancer before the CIN III lesions were used as controls. None of these had HPV positive breast carcinomas. No cases were positive for HPV 11, 18, or 33. HPV 16 was detected in the primary tumours, in local metastases from HPV 16 positive tumours, in a distant HPV 16 positive breast carcinoma metastasis to the colon, and in other primary cancers in patients with HPV 16 positive breast carcinomas and HPV 16 positive CIN III. Estrogen and progesterone receptors were quantified in the HPV positive and HPV negative breast carcinomas, and there was no significant difference in the fraction positive in the two groups. Oncogenic HPV DNA might be transported from an original site of infection to other organs by blood or lymph, and possibly be a factor in the development of cancer in different organs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006162609420
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  • 54
    Electronic Resource
    Electronic Resource
    Genetic anticipation and breast cancer: a prospective follow‐up study (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 21-28 
    Details
    ISSN: 1573-7217
    Keywords: age of diagnosis ; ascertainment ; breast cancer ; genetic anticipation ; prospective cohort family study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Genetic anticipation is characterized by an earlier age of disease onset, increased severity, and a greater proportion of affected individuals in succeeding generations. The discovery of trinucleotide repeat expansion (TRE) mutations as the molecular correlate of anticipation in a number of rare Mendelian neurodegenerative disorders has led to a resurgence of interest in this phenomenon. Because of the difficulties presented to traditional genetics by complex diseases, the testing for genetic anticipation coupled with TRE detection has been proposed as a strategy for expediting the identification of susceptibility genes for complex disorders. In the case of breast cancer, a number of previous studies found evidence consistent with genetic anticipation. It is known that a proportion of such families are linked to either BRCA1 or BRCA2, but no TRE mutations have been identified. It has been shown that the typical ascertainment employed in studies purporting to demonstrate genetic anticipation combined with unadjusted statistical analysis can dramatically elevate the type I error. We re‐examine the evidence for anticipation in breast cancer by applying a new statistical approach that appears to have validity in the analysis of anticipation to data ascertained from a recent follow‐up of a large prospective cohort family study of breast cancer. Using this approach, we find no statistically significant evidence for genetic anticipation in familial breast cancer. We discuss the limitations of our analysis, including the problem of adequate sample size for this new statistical test.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006151132592
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  • 55
    Electronic Resource
    Electronic Resource
    Differential regulation of normal and tumoral breast epithelial cell growth by fibroblasts and 1,25‐dihydroxyvitamin D3 (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 29-39 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; cell interactions ; 1,25‐dihydroxyvitamin D3 ; fibroblast ; normal epithelial cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Mesenchymal‐epithelial interactions are of paramount importance during normal and tumoral breast developments. We have investigated the paracrine growth regulation of normal and tumoral breast epithelial cells by fibroblasts derived from normal or pathological breast tissues. In some cases, breast cancer MCF‐7 cells or normal epithelial cells in primary culture were cocultured with fibroblasts in a Transwell system allowing diffusible factor exchanges. Alternatively, conditioned medium produced by fibroblast cultures was added to epithelial cell cultures. Fibroblasts were shown to stimulate the proliferation of normal and carcinoma cells through paracrine mechanisms. However, the paracrine exchanges appeared to be different in normal versus tumoral breast epithelial cell growth regulation. Moreover, vitamin D‐related compounds that have been proposed as anti‐tumoral drugs were studied for their ability to affect normal and tumoral mammary epithelial cell proliferation and to interfere with the growth‐regulatory activity of fibroblasts. Whereas vitamin D compounds inhibited MCF‐7 cell growth, they led to a marked stimulation of the proliferation of normal mammary epithelial cells. Moreover, it was shown that the vitamin D analog EB 1089 can block the mitogenic effect of fibroblast‐conditioned medium on tumoral but not normal breast epithelial cells. The differential effects of vitamin D compounds on cell proliferation provide further data in favor of the different behaviours of normal and tumoral mammary epithelial cells. The potential therapeutic use of vitamin D derivatives in the treatment of breast cancer is supported by these results but their growth‐stimulatory properties on normal epithelial cells cannot be overlooked.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006163418479
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  • 56
    Electronic Resource
    Electronic Resource
    Regulation of BAX and BCL‐2 expression in breast cancer cells by chemotherapy (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 107-117 
    Details
    ISSN: 1573-7217
    Keywords: apoptosis ; Bax ; Bcl‐2 ; breast cancer ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Optimizing chemotherapeutic drug delivery strategies relies, in part, on identification of the most clinically effective sequence, dose, and duration of drug exposure. The combination of dose intensive etoposide (VP‐16) followed by cyclophosphamide has clinical efficacy in the treatment of advanced breast cancer. However, molecular mechanisms that underlie the effectiveness of this combination of chemotherapeutic agents have not been investigated. In this study we investigated regulation of BAX and BCL‐2 expression by VP‐16 and cyclophosphamide as a potential mechanism for the induction of breast cancer cell death induced by this regimen. There was a dose and time dependent increase in BAX expression in the breast cancer cell lines MCF‐7, MDA‐MB‐435S, and MDA‐MB‐A231 following in vitro treatment with 50–100 μM VP‐16. Elevation of BAX protein expression in the presence of VP‐16 alone did not correlate with reduced viability or induction of apoptosis in MCF‐7, MDA‐MB‐435S, or MDA‐MB‐A231. VP‐16 did effectively block the breast cancer cell lines evaluated (MCF‐7 and MDA‐MB‐435S) at G2/M phase of the cell cycle, confirming activity of the drug in vitro. MCF‐7 and MDA‐MB‐435S cells that were pre‐treated with VP‐16 and subsequently exposed to 1.0–12.0 μg/m1 4‐hydroperoxycyclophosphamide (4HC), an active metabolite of cyclophosphamide, had markedly reduced viability when compared to matched controls treated with either VP‐16 or 4HC individually. Consistent with this loss of viability, exposure of all three cell lines to the combination of VP‐16 and 4HC resulted in higher BAX protein levels than those observed following treatment with either single agent. This combination of chemotherapeutic agents also resulted in reduced BCL‐2 expression. These observations suggest that combination chemotherapy may derive its efficacy, in part, through coordinated regulation of specific gene products associated with apoptosis. Characterization of molecular events that underlie susceptibility of specific tumor cells to combination chemotherapeutic regimens may lead to additional improvements in treatment strategies for this disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006175811676
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    Cathepsin D expression by cancer and stromal cells in breast cancer: an immunohistochemical study of 1348 cases (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 135-145 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; cathepsin D ; immunohistochemistry ; protease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study was aimed at investigating the influence of cathepsin D (CD) expression by cancer cells and stromal cells on breast cancer prognosis. This is a study of 1348 node‐positive (NPBC) and node‐negative (NNBC) breast cancers diagnosed between 1980 and 1986 and with a minimum follow‐up of 5.2 years. CD expression was assessed by immunohistochemistry on archival material using a polyclonal antibody. The expression by cancer and stromal cells was assessed separately and correlated with distant metastasis free (DMFS) and overall survival (OS). Cancer cells expressed CD (more than 10% cells expressing CD) in 38.9% of cases and reactive stromal cells in 43.6%. CD expression by reactive stromal cells, and not cancer cells, correlated with several factors of poor prognosis by cancer cells. A strong association was also found with expression of other proteases (stromelysin‐3, gelatinase A, and urokinase Plasminogen Activator) by these same reactive stromal cells. CD expression by cancer cells did not predict DMFS or OS but, by univariate analysis, CD expression by reactive stromal cells was associated with earlier recurrence and shorter survival in NNBC (p = 0.0425) and NPBC patients submitted to adjuvant chemotherapy (p = 0.0234). However, CD expression by reactive stromal cells remained a significant predictor of recurrence by multivariate analyses only in a subgroup of NPBC submitted to adjuvant chemotherapy. Overall, those data support the concept that proteases produced by reactive stromal cells are under cancer cell stimulation and that CD by stromal cells, and not cancer cells, influences the prognosis, but only in a subgroup of patients with breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006140213493
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    Assessment of quality of life in women undergoing hormonal therapy for breast cancer: validation of an endocrine symptom subscale for the FACT‐B (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 187-197 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; endocrine therapy ; FACT‐B ; FACT‐ES ; quality of life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Existing quality of life instruments do not include adequate items to measure the side effects and putative benefits of hormonal treatments given in breast cancer. We report the development and validation of an 18 item endocrine subscale (ES) to accompany a standardised breast cancer quality of life measure, the Functional Assessment of Cancer Therapy (FACT‐B) [1]. The FACT‐ES (FACT‐B plus ES) was tested initially on 268 women with breast cancer receiving endocrine treatments. Alpha coefficients for all subscales demonstrated good internal consistency (range α = 0.65–0.87). Test‐retest reliability of the ES indicated good stability (r = 0.93, p 〈 0.001). Advanced breast cancer patients' quality of life was high, showing the efficacy of endocrine therapy, but women with primary disease reported better physical, social, and functional well‐being and fewer breast cancer concerns. Most frequently reported symptoms were loss of sexual interest (31%), weight gain (25%), and hot flushes (24%). Significant differences were found between treatment groups for hot flushes and vaginal dryness. Two assessments of the instrument's responsiveness to change were made; 32 women in a clinical trial of endocrine therapy and 18 women without breast cancer taking HRT completed the FACT‐ES at baseline, 4, 8, and 12 weeks. Trial patients reported significantly more symptoms at 8 and 12 weeks than at baseline. Women taking HRT reported significantly fewer or less severe symptoms than at baseline. In conclusion the FACT‐ES has acceptable validity and reliability and is sensitive to clinically significant change, making it suitable for clinical trials of endocrine therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006263818115
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  • 59
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    Electronic Resource
    Induction of insulin‐like growth factor binding protein expression by ICI 182,780 in a tamoxifen‐resistant human breast cancer cell line (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 231-242 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; ICI 182 ; 780 ; IGFBPs ; tamoxifen resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Earlier studies in our laboratory demonstrated that the steroidal antiestrogen ICI 182,780 is very effective in abolishing the tamoxifen‐resistant proliferation of MCF 7/5‐23 cells [1]. In addition, preliminary binding studies showed that ICI 182,780 increased the binding of insulin‐like growth factor (IGF)‐I to the MCF 7/5‐23 cells, although this finding was not the result of an increase in the expression of the insulin‐like growth factor‐I receptor (IGF‐IR). Hence, we reasoned that the inhibition of tamoxifen‐resistant cell growth by ICI 182,780 might have been due to increased expression of insulin‐like growth factor binding proteins (IGFBPs). We observed the up‐regulation of non‐insulin‐suppressible IGF‐I binding in both the tamoxifen‐sensitive MCF 7/5‐21 cell line (1.5‐fold) and the tamoxifen‐resistant MCF 7/5‐23 cell line (2.5‐fold) after 5 days of treatment with ICI 182,780 (10−7 M) in serum‐free medium, suggesting a role for cell‐associated IGFBPs. Affinity cross‐linking experiments confirmed the presence of an IGF‐I:IGFBP complex of approximately 38‐kDa in tamoxifen or ICI 182,780‐treated cells. Western ligand blots showed higher levels of a soluble 30‐kDa IGFBP in media conditioned by either of the subclones that had been treated with ICI 182,780, an effect consistently opposed by estrogen (E2:10−9 M). RT‐PCR showed higher levels of IGFBP‐5 mRNA than any of the other known IGFBPs, suggesting that this was the major IGFBP subtype. The protein was subsequently identified by Western immunoblotting as IGFBP‐5. In conclusion, we postulate that this may be a mechanism contributing to the greater potency of ICI 182,780 in the growth inhibition of the MCF 7/5‐23, tamoxifen‐resistant cell line.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006274712664
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  • 60
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    A study on the cost effectiveness of sestamibi scintimammography for screening women with dense breasts for breast cancer (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 243-258 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; cost effectiveness ; dense breasts ; mammographic parenchymal patterns ; Sestamibi scintimammography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The potential impact of Sestamibi scintimammography (SSMM) on the cost effective management of women with dense breasts is not known. This study addresses this issue quantitatively by examining the impact of SSMM based screening strategies on the ∼3,000,000 women over 40 with very dense breasts (DY patterns) without palpable masses and who have had one or more prior mammograms, who undergo routine screening each year. Quantitative decision tree sensitivity analysis was used to compare the conventional mammography (MM) strategy (strategy A), which does not subject patients with negative mammograms to any further examination until their next screening, with two decision strategies for screening with SSMM SSMM after a negative mammogram (strategy B) or SSMM as the only screening test for women already identified as having dense breasts by a previous mammogram (strategy C). Cost effectiveness was measured by calculating the incremental cost effectiveness ratio (ICER) of strategies B and C, which is the cost of achieving an additional year of life in the screening population by choosing a SSMM based decision strategy rather than the conventional strategy. Strategies B and C reduced the number of false negative diagnoses by 62% and 8%, respectively. The ICER was $632,000 and $3.18M per life year for strategy B and C, respectively. To be cost effective, the pre‐test probability of cancer in the study population must be greater than 3% for strategy B or the cost of SSMM must be less than $50 for strategy C. These results show the ICER of an SSMM based breast cancer screening strategy in the management of patients with dense breasts is not currently within the range (∼$50,000 per year life saved) of other commonly performed medical interventions that are considered cost effective.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006211817207
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  • 61
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    Electronic Resource
    Vorozole results in greater oestrogen suppression than formestane in postmenopausal women and when added to goserelin in premenopausal women with advanced breast cancer (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 25-34 
    Details
    ISSN: 1573-7217
    Keywords: aromatase inhibition ; breast cancer ; formestane ; GnRH agonist ; goserelin ; pharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The high potency and selectivity of new aromatase inhibitors has translated to greater efficacy and improved tolerability in comparison with established second‐line hormonal agents for advanced breast cancer in phase III clinical trials. Two pharmacological studies are reported which assess the use of one of these inhibitors, vorozole, in combination or comparison with well‐established methods of oestrogen deprivation in pre and postmenopausal patients. When combined with the gonadotrophin‐releasing hormone agonist (GnRHa) goserelin in 10 premenopausal patients, vorozole markedly enhanced the suppression of serum levels of oestrone, oestradiol and, oestrone sulphate beyond that achieved by goserelin alone (by a mean 74%, 83%, and 89%, respectively). The combination was well‐tolerated and had no significant effects on androgen levels. Vorozole was compared with formestane in 13 postmenopausal women and serum oestrone, oestradiol, and oestrone sulphate levels were suppressed by 47%, 30%, and 70%, respectively, more by vorozole than by the steroidal aromatase inhibitor. Again the tolerability was excellent. The plasma oestrogen levels in the postmenopausal patients on vorozole were lower than in the premenopausal patients on goserelin plus vorozole, indicating that ovarian oestrogen synthesis may be relatively resistant to aromatase inhibition, even during GnRHa treatment. Thus, in both pre and postmenopausal patients substantially greater suppression of oestrogen can be achieved by vorozole compared with alternative approaches. Existing clinical–pharmacological correlates suggest that these increases in pharmacological effectiveness may result in enhanced clinical effectiveness.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006289811540
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    Electronic Resource
    Hsp27 overexpression inhibits doxorubicin–induced apoptosis in human breast cancer cells (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 185-194 
    Details
    ISSN: 1573-7217
    Keywords: apoptosis ; breast cancer ; doxorubicin ; hsp27 ; topoisomerase II
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previously we demonstrated that heat shock protein 27 (hsp27) overexpression confers resistance to the chemotherapeutic agent doxorubicin in MDA–MB–231 breast cancer cells. Since induction of apoptosis is one underlying mechanism of chemotherapeutic drug action, we investigated the effect of hsp27 overexpression on doxorubicin–induced apoptosis, finding that hsp27 protects MDA–MB–231 cells from apoptosis. We also examined expression of the doxorubicin target, topoisomerase II (topo II), in control and hsp27–overexpressing stable transfectants, as topo II expression is important for both drug sensitivity and the initiation of apoptosis by doxorubicin. The relative levels of both topo IIα and β were higher in the controls than the hsp27–overexpressing clones, suggesting that the apoptotic protective effect of hsp27 overexpression in MDA–MB–231 cells is associated with altered topo II expression.abstract
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006207009260
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    pS2 (TFF1) levels in human breast cancer tumor samples: correlation with clinical and histological prognostic markers (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 251-263 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; mRNA ; pS2 ; prognostic marker ; RT–PCR ; TFF1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The expression of pS2 (TFF1) has been previously shown to identify patients with improved response to anti–hormonal therapy and more favorable outcome. In the current study, 100 human breast carcinoma samples obtained from the Manitoba Breast Tumor Bank were analyzed for pS2 mRNA using a quantitative, competitive reverse transcriptase–polymerase chain reaction (qcRT–PCR) assay. A pS2/ß–actin cut–off criterion of 0.010 was established to classify tumors as either pS2 positive or pS2 negative. pS2 mRNA levels were positively associated with both ER and PR, with the majority of ER+ (59) and PR+ (60) tumors also being positive for pS2. In addition, a significant linear correlation was observed between the amount of pS2 mRNA and ER (p〈0.0001) and PR (p〈0.0001) protein. pS2 mRNA levels also exhibited an inverse association with tumor size and histological grade, consistent with the observation that pS2 is primarily expressed in small (T 〈 2.0 cm), but well differentiated tumors (Grades I and II). No associations were observed with tumor cell type, patient age, or lymph node status. The strong correlation displayed between pS2 and a number of currently used breast cancer prognostic markers supports the clinical use of pS2 to further assess tumor status and patient outcome.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006215310169
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  • 64
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    Electronic Resource
    Synergistic action of apoptosis induced by eicosapentaenoic acid and TNP‐470 on human breast cancer cells (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 147-158 
    Details
    ISSN: 1573-7217
    Keywords: angiogenesis inhibitor ; apoptosis ; Bcl‐2 ; breast cancer ; eicosapentaenoic acid ; TNP‐470
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of eicosapentaenoic acid (EPA) and an angiogenesis inhibitor (TNP‐470) on the suppression of breast cancer cell growth were examined in five human breast cancer cell lines (MDA‐MB‐231, T‐47D, MCF‐7, KPL‐1, and MKL‐F). In all five cell lines, EPA and TNP‐470 alone both showed tumor growth inhibition in a time‐ and dose‐dependent manner, and in combination, a synergistic effect was seen at high concentrations. EPA plus TNP‐470 treatment evoked apoptosis as confirmed by the appearance of sub G1 populations, by DNA fragmentation, and by cell morphology. With the combination, the expression of Bax and Bc1‐xS, the apoptosis‐enhancing proteins, was more up‐regulated and that of Bcl‐2 and Bcl‐xL, the apoptosis‐suppressing proteins, was more down‐regulated compared to the use of EPA or TNP‐470 alone, suggesting that their synergistic effect was due to an acceleration of apoptosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006283131240
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  • 65
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    Electronic Resource
    Down‐regulation of gelsolin expression in human breast ductal carcinoma in situ with and without invasion (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 177-186 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; ductal carcinoma in situ (DCIS) ; gelsolin ; prognostic features
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Expression of gelsolin, an actin filament regulatory protein, in human breast ductal carcinoma in situ (DCIS) was analyzed by immunohistochemistry using a monoclonal antibody. Formalin‐fixed paraffin‐embedded tissues from 59 pure DCIS specimens and 33 DCIS specimens with associated invasive components were evaluated for gelsolin reactivity and compared to eight normal breast cases and 76 invasive breast cancers. The proportion of cases exhibiting negative/low expression of gelsolin in the epithelium was as follows – normal, 0%; pure DCIS, 56%; DCIS associated with invasion, 58% in the DCIS component and 66% in the invasive component; invasive carcinoma, 70%. These data demonstrate that down‐regulation of gelsolin expression in breast epithelium frequently parallels progression to malignancy. Testing gelsolin expression (normal vs. negative/low levels) in the DCIS lesions for associations with patient age or any of the following histopathologic parameters revealed no significant (95% probability level) correlations – tumor size; pathologic (Van Nuys system) grade; nuclear grade; necrosis; presence of histologic calcifications; presence or type of adjacent benign lesions; architectural histologic pattern; and mammographic extent. Gelsolin loss was more commonly associated with mammographic soft tissue lesions as compared to calcified lesions (P = 0.009). A positive trend of borderline significance (P = 0.06) found in the DCIS with invasion group was a correlation between down‐regulated gelsolin expression in the DCIS component and size (〈 versus ≥ 15 mm) of the invasive tumor. In conclusion, reduced gelsolin protein is detectable in at least half of breast lesions which have progressed to DCIS. The trend between increasing gelsolin loss and malignant progression from normal epithelium to DCIS to invasive breast cancer (P 〈 0.0001) suggests additional investigation is needed to determine the potential of altered gelsolin expression as a marker for prognosis and for therapeutic interventions in breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006203632228
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  • 66
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    Electronic Resource
    Anti‐human procathepsin D activation peptide antibodies inhibit breast cancer development (1999)
    Springer
    Breast cancer research and treatment 57 (1999), S. 261-269 
    Details
    ISSN: 1573-7217
    Keywords: activation peptide ; antibodies ; breast cancer ; immunotherapy ; procathepsin D
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Enzymatically inactive procathepsin D secreted from cancer cells has been confirmed to play a role in development of human breast cancer. In the present study, we focused on the role of activation peptide which was in our preliminary studies suggested to be most probably responsible for mitogenic activity of procathepsin D. Using synthetic fragments and antibodies raised against individual fragments, we demonstrated that the growth factor activity of activation peptide is localized in a nine amino acid stretch (AA 36–44) of activation peptide and moreover both anti‐activation peptide and anti‐ 27–44 peptide antibodies administered in vivo inhibited the growth of human breast tumors in athymic nude mice. Taking into account our previous results and presented data, we hypothesize that the interaction of procathepsin D activation peptide with an unknown surface receptor is mediated by a sequence 36–44 plus close vicinity. We also propose that this interaction leads in certain types of tumor derived cell lines to proliferation and higher motility. Blocking of the interaction of activation peptide by specific antibodies or antagonists might be a valuable tool in breast cancer inhibition.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006238003772
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  • 67
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    Coexpression of c-kit and stem cell factor in breast cancer results in enhanced sensitivity to members of the EGF family of growth factors (1999)
    Springer
    Breast cancer research and treatment 58 (1999), S. 1-10 
    Details
    ISSN: 1573-7217
    Keywords: Akt ; breast cancer ; c-kit ; EGF ; ERK ; heregulin ; stem cell factor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Kit, a tyrosine kinase growth factor receptor, and its ligand, stem cell factor (SCF), are commonly coexpressed in breast cancer. We have previously shown that MCF7 cells (that naturally express SCF) transfected with a c-kit expression vector exhibit enhanced growth in serum-free medium supplemented with IGF-1. Consequently, we wished to examine the interaction of Kit/SCF with additional growth factors important in the biology of breast cancer. MCF7 transfectants expressing Kit, cultured in serum-free medium supplemented with EGF, displayed more than twice the growth of controls at identical EGF concentrations. Similar responses were seen in the presence of heregulin. The specificity of the Kit-mediated response was illustrated by a reduction in heregulin-stimulated growth in the presence of a monoclonal antibody directed against the Kit receptor. In addition, EGF- and heregulin-stimulated growth of the ZR75-1 cell line that naturally coexpresses Kit and SCF was also inhibited by the Kit blocking antibody. Preliminary investigations into the signal transduction pathways activated by these growth factors revealed that SCF activated both the Ras-MAP kinase and phosphatidyl-inositol-3-kinase (PI3 kinase) pathway. Both EGF and heregulin activated MAPK but to a lesser degree than SCF, and combination of SCF with these growth factors resulted in enhanced MAPK activation. Assessment of PI3K pathway activation using anti-phospho-Akt antibodies revealed that EGF was a poor activator of Akt; activation of this pathway was markedly enhanced by the addition of SCF. Heregulin activated Akt and addition of SCF provided no further activation. Taken together these results suggest that coexpression of SCF and Kit may enhance responsiveness to erbB ligands by enhancing activation of the MAPK and PI3K pathways.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006272527435
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    Hypermethylation of the Wilms' tumor suppressor gene CpG island in human breast carcinomas (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 35-43 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; CpG island ; DNA hypermethylation ; Wilms' tumor suppressor gene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract CpG island hypermethylation is known to be associated with transcriptional silencing of tumor suppressor genes in neoplasia. We have previously detected aberrantly methylated sites in the first intron of the Wilms' tumor suppressor (WT1) gene in breast cancer. In the present study, we extended the investigation to a CpG island located in the promoter and first exon regions of WT1. Methylation of this CpG island was found to be extensive in MCF‐7 and MDA‐MB‐231 breast cancer cells, as well as in 25% (five of 20 patients) of primary breast tumors. While levels of the known 3.0‐kb WT1 mRNAs were decreased or not detected in these cell lines, the expression could be partially restored following treatment with a demethylation agent, 5‐aza‐2′‐deoxycytidine. Surprisingly, a novel 2.5‐kb WT1 transcript was expressed at high levels in both untreated and treated MDA‐MB‐231 cells. This novel transcript was likely a WT1 variant missing the first exon, and therefore escaped the methylation control present in the normal transcript. Our study implicates the future need to investigate the significance of this aberrant transcript as well as the role of WT1 CpG island hypermethylation in breast neoplasia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006222803788
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  • 69
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    Electronic Resource
    Breast cancer and timing of surgery during menstrual cycle: a 5‐year analysis of 248 premenopausal women (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 259-266 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; menstrual cycle phase ; premenopausal ; prognosis ; surgery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the present report, we retrospectively analyzed the impact of the timing of surgery during menstrual cycle on disease‐free and overall survival of 248 premenopausal patients with stage I/Il breast cancer who underwent surgery followed by anthracycline‐containing adjuvant chemotherapy. With a median follow‐up of 5 years, no statistically significant differences were observed in disease‐free or overall survival between women operated upon during the follicular (days 0–14) and the luteal (days 15–32) phase of the menstrual cycle. The impact on disease‐free and overall survival of lymph‐node status, tumor size and hormone receptor expression, but not of the phase of the menstrual cycle at the time of surgery, was confirmed by univariate and multivariate analysis. However, when combined with hormone receptor status, the phase of the menstrual cycle at the time of surgery proved useful to better define the prognosis of primary breast cancer patients, with significantly longer disease‐free and overall survival for patients operated upon during the follicular phase and with positive hormone receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006276120841
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  • 70
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    Early age at menopause and breast cancer: are leaner women more protected? A prospective analysis of the Dutch DOM cohort (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 285-291 
    Details
    ISSN: 1573-7217
    Keywords: body mass index ; breast cancer ; menopause ; smoking
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To investigate the relationship between age at menopause, body mass index, and breast cancer risk, we used data from a prospective cohort study (DOM cohort) in the Netherlands. Participants in this breast cancer‐screening project included 10,591 women living in Utrecht, aged 49–66 years at enrolment. During a median follow‐up period of 19 years, women attended screening rounds at which anthropometric measurements were taken and questions were asked about menopausal status, age at menopause, medication use and other risk factors for breast cancer. Cox regression analysis was used to investigate the relationship between age at menopause and subsequent breast cancer risk. Breast cancer incidence decreased with an earlier age at menopause. Women with a menopausal age of 44 years or younger had a 34% lower risk of breast cancer, than women with a menopausal age over 54 years (hazard ratio is 0.66 (95% confidence interval 0.43–0.91)). The annual hazard of breast cancer incidence decreased by 2.6% per year reduction in age at menopause. The protective effect of an early age at menopause was stronger for women with a low body mass index (≤27 kg/m2; reduction of 44%) than for women with a high body mass index (〉27 kg/m2; reduction of 24%), although this difference was not statistically significant (P for interaction = 0.58). This difference was most pronounced in women who had ever smoked. Adjustment for known breast cancer risk factors did not alter the crude risk estimates significantly. In conclusion, this study provides evidence of the protective effect of lower age at menopause on subsequent breast cancer risk. This protective effect may be even stronger in leaner women.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006277207963
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    Suppression of parathyroid hormone‐related protein messenger RNA expression by medroxyprogesterone acetate in breast cancer tissues (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 11-23 
    Details
    ISSN: 1573-7217
    Keywords: androgen receptor ; bone metastasis ; breast cancer ; medroxyprogesterone acetate ; parathyroid hormone‐related protein ; progesterone receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The level of parathyroid hormone‐related protein (PTHrP) expressed in breast cancer tissue is closely related to the incidence of bone metastasis. We examined the PTHrP mRNA expression in breast cancer tissues by coamplification polymerase chain reaction (PCR) in mole ratio to internal standard β‐actin mRNA. The PTHrP expression was higher in premenopausal patients than in postmenopausal patients (P〈0.05). More pronounced difference by menopause found in estrogen receptor (ER) positive groups (P〈0.001) indicated that the PTHrP expression in breast cancer tissue is hormonally regulated and might be altered by endocrine agents. To clarify the changes of PTHrP expression by endocrine therapy of breast cancer, we measured PTHrP expression in the breast cancer tissue incubated for 24 h with 1 × 10−8 M of estradiol (E2), 1 × 10−6 M of tamoxifen (TAM) and 1 × 10−5 M of medroxyprogesterone acetate (MPA). The PTHrP expression was decreased significantly by MPA (P〈0.005), while E2 and TAM did not change the PTHrP expression. Progesterone receptor (PgR) mRNA expression was also examined to confirm that the breast cancer tissue responds to E2 and TAM. The results were well compatible with the better therapeutic effect of MPA reported for the treatment of breast cancer with bone metastases. As a potential candidate for the receptor that mediates the suppressive effect of MPA, androgen receptor (AR) is suggested most probable. Present results also demonstrated that the clinical response of individual tumors is closely associated with the early in vitro changes of gene expression detected in the cancer specimen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006254006088
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  • 72
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    Electronic Resource
    Quality of life in the first year after breast cancer surgery: rehabilitation needs and patterns of recovery (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 45-57 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; psychological distress ; quality of life ; rehabilitation needs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. Although mortality rates from breast cancer are declining, many breast cancer survivors will experience physical and psychological sequelae that affect their everyday lives. Few prospective studies have examined the rehabilitation needs of newly diagnosed breast cancer patients, and little is known about the predictors of health‐related quality of life (QOL) in this population. Methods. Between 1987 and 1990, 227 women with early stage breast cancer participated in a prospective longitudinal study in which detailed information was collected through interviews, standardized measures of QOL and psychological distress, and clinical evaluation. Comparisons of physical and treatment‐related problems were made according to type of surgical treatment. Multivariate regression analysis was performed to examine the predictors of QOL at one year after surgery. Results. Physical and treatment‐related problems were reported frequently one month after breast cancer surgery, and occurred with equal frequency in women receiving modified radical mastectomy or breast conservation treatment. There were no significant differences in problems reported at one year by type of surgery; however, frequently reported problems include ‘numbness in the chest wall or axilla,’ ‘tightness, pulling or stretching in the arm or axilla,’ ‘less energy or fatigue,’ ‘difficulty in sleeping,’ and ‘hot flashes’. There was no relationship between the type of surgery and mood or QOL. Poorer QOL one year after surgery was significantly associated with greater mood disturbance and body image discomfort one month after surgery, as well as positive lymph node involvement. Although the majority of patients experienced substantial disruptions in the physical and psychosocial dimensions of QOL post‐operatively, most women recovered during the year after surgery, with only a minority (〈10%) significantly worsening during that time. Conclusions. At one year after surgery, most women report high levels of functioning and QOL, with no relationship between the type of surgery and QOL. Women who reported lower levels of QOL at one year after diagnosis had greater mood disturbance and poorer body image one month after surgery, as well as lower income and positive axillary nodes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006214830854
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  • 73
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    Electronic Resource
    Postoperative chemo–endocrine treatment with mitomycin C, tamoxifen, and UFT is effective for patients with premenopausal estrogen receptor–positive stage II breast cancer (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 111-122 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; estrogen receptor ; mitomycin C ; postoperative chemotherapy ; tamoxifen ; UFT
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effectiveness of combining mitomycin C (MMC), tamoxifen (TAM), and 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) was evident in patients with estrogen receptor-positive (ER+) breast cancers. UFT, an oral preparation of tegafur and uracil at a molar ratio of 1:4, was reported to have higher antitumor effects than tegafur alone for patients with breast cancer. Therefore, the combined chemotherapy of MMC, TAM and UFT may possibly be effective for breast cancer. From 1988 to 1991, we studied the effects of postoperative adjuvant therapy for Japanese women with stage II breast cancer, all seen at 71 institutions in western areas of Japan. Five hundred and ninety four patients with stage II primary breast cancer who had undergone curative surgery, including total mastectomy and axillary lymph node dissection, were enrolled. On the day of surgery, each patient was given 13 mg/m2 of MMC intravenously. Patients with ER+ tumors were then assigned to group A or group B. Group A received 30 mg/day of TAM given orally from postoperative 2 weeks, for 2 years. Group B was additionally given an oral dose of 300 mg/day of UFT for 2 years, given concomitantly with 30 mg/day of TAM. Patients with ER− tumors were assigned to group C or group D. Group C were prescribed 300 mg/day of UFT, orally, from postoperative 2 weeks for 2 years, and group D were additionally given an oral dose of 30 mg/day of TAM together with 300 mg/day of UFT. There were no differences among the groups regarding prognostic factors or doses of MMC and TAM in ER+ patients and MMC and UFT in ER− patients. Toxicity rates for leukopenia, anorexia, and nausea/vomiting were higher in group B than in group A patients. There were no statistical differences in the overall survival and disease–free survival times between groups A and B, or groups C and D, for all eligible cases. In a retrospective subgroup analysis using Bonferroni's adjustments, the additional effect of UFT on the combined treatment of MMC and TAM lengthened the disease-free survival time for patients with premenopausal ER+ cancers (corrected P value by Bonferroni's adjustments 〈0.05). Multivariate analysis showed that effects of the combined treatment of MMC, TAM, and UFT was significantly related to the menopausal status (P〈0.0 1). Our findings show that postoperative ingestion of MMC, TAM, and UFT was effective for patients with premenopausal ER+ stage II breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006221425652
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  • 74
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    Electronic Resource
    Expression of inducible nitric oxide synthase in human breast cancer depends on tumor grade (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 143-149 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; immunohistochemistry ; nitric oxide synthases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Expression of inducible nitric oxide synthase (iNOS) by tumor cells has been suggested to abrogate metastasis in several tumor models, whereas constitutive NOS expression correlated positively with tumor grade in human breast carcinoma. Whether or not expression of one of the various NOS isoforms could predict the prognosis of breast cancer, however, has not been established. In the present report we investigated the cellular distribution of NOS isoforms in a series of benign and malignant breast tumors and in normal breast tissue. Immunohistochemistry revealed that in samples of benign disease the number of iNOS + epithelial cells or total epithelial cells was 69 ± 16% (n=50). In samples of grade II invasive ductal breast carcinomas the number of iNOS+ tumor cells or total tumor cells was 62 ± 20 (n=40), compared to 12 ± 9 (n=40) in samples of grade III carcinomas (P 〈 0.0001). iNOS protein was also identifiable in most of the epithelial cells of normal breast tissue (n=4). In contrast, eNOS protein was restricted to vascular endothelial cells in all of the specimens studied. Since the presence of tumor cell iNOS protein is inversely related to the tumor’s metastatic potential, we conclude that endogenous tumor cell mediated iNOS expression might have an inhibitory effect on the metastatic process in breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006288526311
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  • 75
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    Electronic Resource
    PACAP (6–38) is a PACAP receptor antagonist for breast cancer cells (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 175-184 
    Details
    ISSN: 1573-7217
    Keywords: PACAP ; VIP ; breast cancer ; proliferation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of pituitary adenylate cyclase activating polypeptide (PACAP) analogs were investigated using breast cancer cells. 125I–PACAP–27 bound with high affinity (Kd=5 nM) to T47D cells (Bmax = 29,000 per cell). Specific 125I–PACAP–27 binding was inhibited half maximally by PACAP–27, PACAP–38, PACAP(6–38) and PACAP(28–38) with IC50 values of 8, 17, 750 and 〉3000 nM, respectively. By RT–PCR, PACAP receptor mRNA was present in MCF–7 and T47D cell lines. Polyclonal antibodies to a PACAP receptor fragment (A–8–C) were elicited. The antibodies were affinity purified, recognized a 60–kDa protein by western blot, and stained malignant cells in breast cancer biopsy specimens by immunohistochemistry. PACAP–27 elevated the cAMP in T47D cells and the increase in cAMP caused by PACAP was inhibited by PACAP(6–38). PACAP–27 stimulated c–fos mRNA in T47D cells and the increase in c-fos gene expression caused by PACAP was reversed by PACAP (6–38). PACAP (6–38) inhibited colony formation using a soft agar assay and inhibited breast cancer xenograft growth in nude mice. These data suggest that PACAP (6–38) functions as a breast cancer PACAP receptor antagonist.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006262611290
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  • 76
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    Electronic Resource
    Changes in body composition during breast cancer chemotherapy with the CMF‐regimen (1999)
    Springer
    Breast cancer research and treatment 57 (1999), S. 285-290 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; chemotherapy ; CMF ; weight gain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Weight gain is a reported problem associated with adjuvant chemotherapy for breast cancer and often generates psychosocial stress in women [1]. It also may affect prognosis and survival. Changes in body composition and weight during chemotherapy, particularly adjuvant treatment of breast carcinoma, have been previously reported [1–3]. Multiple reasons for this weight gain have been suggested though few theories have been scientifically validated [4]. The aim of this study was to investigate body composition and its relationship to weight change associated with the CMF‐based breast cancer chemotherapy protocols. Total body nitrogen (TBN), body fat, total body water (TBW), and anthropometric measurements were conducted on 25 female out‐patients (median age 47, range 26–70 years) receiving adjuvant CMF‐based chemotherapy for breast cancer. Total body nitrogen was measured using the In Vivo Neutron Capture Analysis (IVNCA) technique (on day 1 of cycles 2–6) and TBP was calculated by multiplying TBN by 6.25 [5]. Nitrogen Index (NI) was calculated by expressing TBN as a percentage of normal. There was a significant increase in mean body weight during chemotherapy of 2.35 kg (p〈0.0001). Serial measurements showed no significant change in mean TBN, NI, or percentage body fat. Break down of body weight showed a significant increase in mean TBW of 0.79 kg (p=0.003) and mean fat mass of 1.49 kg (p=0.008). We conclude that weight gain observed during adjuvant chemotherapy for breast carcinoma is primarily due to an increase in fat and TBW.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006220510597
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  • 77
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    Electronic Resource
    Involvement of nuclear steroid/thyroid/retinoid receptors and of protein kinases in the regulation of growth and of c‐erbB and retinoic acid receptor expression in MCF‐7 breast cancer cells (1999)
    Springer
    Breast cancer research and treatment 58 (1999), S. 171-181 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; c‐erbB ; cross‐talk regulation ; RAR ; retinoid ; steroid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Nuclear steroid/thyroid/retinoid receptors and c‐erbB membrane receptor tyrosine kinases control epithelial growth and differentiation. Retinoid receptors can dimerize with the vitamin D receptor, the glucocorticoid receptor or the thyroid receptor. Furthermore, multiple c‐erbB receptor dimers have been identified. It has been shown that some of these receptor pathways communicate with each other via cross‐connected regulatory networks. Molecular interactions between retinoid receptors or estrogen receptors (ER) and c‐erbB‐2, and between ER and retinoic acid receptor(RAR)‐α have been reported. Here, we demonstrate the effects of steroids/thyroids/retinoids and of activators of protein kinase A (forskolin, Forsk) and C (12‐O‐tetradecanoylphorbol‐13‐acetate, TPA), on growth and expression of c‐erbB and RARs in MCF‐7 breast cancer cells, which contain high levels of RAR‐α and ‐γ, and which express significant amounts of c‐erbB‐2 and ‐3. All trans‐retinoic acid (tRA), the anti‐estrogen ICI 182 780 (ICI), Forsk and TPA reduced, whereas triiodothyronine and 17β‐estradiol (E2) stimulated cell growth. Flow cytometry revealed that tRA and E2 reduced c‐erbB‐2 and ‐3, whereas tamoxifen, Forsk and TPA up‐regulatedc‐erbB‐2. c‐erbB‐3 was co‐regulated with c‐erbB‐2. Northern analysis demonstrated that RAR‐α was down‐regulated by dexamethasone, ICI, and TPA, whereas vitamin D3 and E2 up‐regulated RAR‐α. RAR‐γ expression was less responsive to such treatment, being reduced only by ICI and Forsk. These data indicate that nuclear receptor and protein kinase signaling communicate with each other and control the expression of RARs and c‐erbB receptors. Efficient growth control requires the coordinated interplay of both receptor systems.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006377006816
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  • 78
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    Electronic Resource
    Quantitation of erbB-2 gene copy number in breast cancer by an improved polymerase chain reaction (PCR) technique, competitively differential PCR (1999)
    Springer
    Breast cancer research and treatment 58 (1999), S. 211-215 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; gene amplification ; polymerase chain reaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A new method of measuring gene copy number in small samples of DNA was used to measure amplification of the erbB-2 gene and a reference gene in breast cancers. The method, termed 'competitively differential polymerase chain reaction' (CD-PCR), combines the advantages of two other techniques for measuring amplification by PCR, namely differential PCR (D-PCR) and competitive PCR (C-PCR). The CD-PCR methodology was evaluated for sensitivity and specificity by comparing amplification measured by CD-PCR with that obtained by fluorescence in situ hybridization (FISH), C-PCR, and Southern blotting analysis. CD-PCR analysis proved to be an accurate predictor of amplification. CD-PCR also overcomes the problems involved in variation of PCR efficiencies and DNA concentrations in tumor samples, and the problems caused by the plateau effect in PCR.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006367700783
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  • 79
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    Electronic Resource
    Influence of estrogen receptor variants on the determination of ER status in human breast cancer (1999)
    Springer
    Breast cancer research and treatment 58 (1999), S. 217-223 
    Details
    ISSN: 1573-7217
    Keywords: estrogen receptor variant mRNAs ; estrogen receptor status ; immunohistochemistry ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Determination of estrogen receptor alpha (ER) status in breast cancer is an important predictive factor for clinical response to endocrine therapy. We have recently shown that discrepancies in ER status determined by immunohistochemical assay (ER-IHA) can occur between amino-terminal (1D5) and carboxyl-terminal (AER-311) targeted ER antibodies and that those tumors which demonstrate discordance are associated with increased expression of truncated ER variant mRNAs. In this study, we have explored this observation to examine if ER variant expression can exert a direct effect on ER-IHA or whether this association is attributable to the characteristics of the antibodies. ER negative cos-1 cells were transfected with expression vectors containing wild type ER (wt-ER) and/or a frequently expressed truncated variant, ER-clone-4 variant. We found that ER-IHA performed with the same N- and C-terminal targeting ER antibodies on cos-1 cells expressing wt-ER alone demonstrated no difference in signals by western blot (P〉0.1). However, co-expression of wt-ER and the truncated ER-clone-4 variant, resulted in discordant IHA results with relatively higher ER-IHA H-scores from N-terminal antibodies (P〈0.03). Furthermore, re-examination of a subset of breast tumors previously studied by ER-IHA showed persistent concordance in 4/5 cases and persistent differences in 3/5 cases with a different pair of ER antibodies. We conclude that the presence of truncated ER variant proteins can interfere with the interpretation of ER status determined by IHA and that this may account for some of the inconsistencies between ER status and response to endocrine therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006375902601
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  • 80
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    Electronic Resource
    Occupational physical activity and risk for breast cancer in a nationwide cohort study in Sweden (1999)
    Springer
    Cancer causes & control 10 (1999), S. 423-430 
    Details
    ISSN: 1573-7225
    Keywords: breast cancer ; physical activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: Our purpose was to investigate effects of physical activity on risk for breast cancer. Methods: From the Swedish nationwide censuses in 1960 and 1970 we defined three partly overlapping cohorts of women whose occupational titles allowed reproducible classification of physical demands at work in 1960 (n=704,904), in 1970 (n=982,270), or with the same demands in both 1960 and 1970 (n=253,336). The incidence of breast cancer during 1971–89 was ascertained through record linkage to the Swedish Cancer Register. We used Poisson regression to estimate relative risks (RR). Results: A total of 20,419, 22,840, and 8261 breast cancers, respectively, were detected in the three cohorts. In all three cohorts the risk for breast cancer increased monotonically with decreasing level of occupational physical activity and with increasing socioeconomic status. Among women with the same estimated physical activity level in 1960 and 1970 the RR was 1.3 for sedentary as compared with high/very high activity level (95% CI 1.2–1.4; p for trend〈0.001). Adjustment for socioeconomic status virtually eliminated this association (RR 1.1; 95% CI 0.9–1.2; p for trend 0.12) leaving a statistically significant 30% gradient only among women aged 50–59 years at follow-up. The association between socioeconomic status and breast cancer risk was largely unchanged after adjustment for occupational physical activity. Conclusion: The protective effect of occupational physical activity on breast cancer risk, if any, appears to be confined to certain age groups.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008922205665
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  • 81
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    Electronic Resource
    Microvessel density and vascular basement membrane immunostaining in tumours of the breast (1999)
    Springer
    Angiogenesis 3 (1999), S. 175-180 
    Details
    ISSN: 1573-7209
    Keywords: angiogenesis ; breast cancer ; collagen IV ; heparan sulphate proteoglycan ; laminin ; vascular basement membrane
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There is a well established correlation between increased breast tumour microvessel density (MVD) and reduced prognosis. The aims of this study were to investigate (1) if MVD is elevated in regions other than `hotspots' of node positive versus node negative breast tumours, and (2) to quantitate the percentage of vessels without vascular basement membrane (VBM) components in high vascular density (HVD) and average vascular density (AVD) regions of node positive and node negative breast tumours. Serial sections were immunostained for CD31 and double-stained for CD31 and collagen IV (CollIV), laminin (LAM) or heparan sulphate proteoglycan (HSPG). Microvessel counts were obtained from HVD and AVD regions and the number of VBM positive vessels were expressed as a percentage of total CD31 positive vessels. MVD was significantly higher in both the HVD and AVD regions of node positive compared with node negative breast tumours (t-test; P 〈 0.03). The average percent vessels positive for CollIV, LAM or HSPG ranged from 18%–45% and did not differ between node positive and negative breast tumours (t-test; P 〉 0.05). No differences were observed in VBM immunostaining between regions of HVD and AVD (t-test; P 〉 0.05). These results demonstrate that vascular density is elevated throughout node positive breast tumours, rather than just in `hotspots', and show that there is no apparent difference in the percentage of VBM-naked vessels in node positive versus node negative breast tumours.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009035123733
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  • 82
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    Electronic Resource
    The methodology of quantitation of microvessel density and prognostic value of neovascularization associated with long‐term survival in Japanese patients with breast cancer (1999)
    Springer
    Breast cancer research and treatment 53 (1999), S. 19-31 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; long‐term survival ; microvessel density ; neovascularization ; quantitation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study updates results on methodology of quantitation of tumor neovascularization and those on the prognostic value of microvessel density (MVD) in breast cancer tissue previously published in the World J. Surg. 21: 49–56, 1997. The follow‐up period of observation of the series was extended to 20 years, and new biological indicators (i.e., proliferating cell nuclear antigen (PCNA), c‐erbB‐2, and p53) were included in the analysis. There were 109 patients with primary breast cancer, from 1971 to 1979, followed up for a median of 14 years (range, 1–20). A representative median longitudinal section of each breast tumor was immunohistochemically stained with factor VIII‐related antigen and analyzed. The three methods of identifying MVD were: (1) average microvessel count (AMC)/mm2, (2) central microvessel count (CMC)/mm2, and (3) highest microvessel count (HMC)/mm2. Thirty‐one patients (28.4%) died of breast cancer. There was a relationship between MVD and peritumor blood vessel invasion (AMC: p = 0.0114, CMC: p = 0.0319, and HMC: p = 0.0009). However, there was no relationship between MVD and other factors. Univariate analysis showed that node status (p 〈 0.0001), histological grade (p 〈 0.0001), clinical tumor size (T) (p = 0.0002), PCNA (p = 0.0033), p53 (p = 0.0043), mitotic grade (p = 0.0092), AMC (p = 0.0214), and peritumor lymphatic vessel invasion (p = 0.0467) were significantly predictive of overall survival. HMC was borderline significant (p = 0.0702), while CMC and c‐erbB‐2 were not significant. Multivariate analysis showed that T (p = 0.0005), node status (p = 0.0053), and AMC (p = 0.0485) were independent factors, but neither CMC nor HMC was independent. AMC, a significant independent prognostic factor, might be a better method than the others for evaluating angiogenesis, but further and larger studies are warranted.
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    URL: http://dx.doi.org/10.1023/A:1006193024382
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  • 83
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    Prognostic factors in patients with isolated recurrences of breast cancer (stage IV-NED) (1999)
    Springer
    Breast cancer research and treatment 53 (1999), S. 105-112 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; combined modality therapy ; isolated recurrences ; radiation therapy ; surgery ; systemic therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: One to 10% of women with metastatic breast cancer have a recurrence of their disease as an isolated lesion (local, regional, or distant) which may be treated by surgical resection, irradiation, or both. These are patients with stage IV breast cancer with no evidence of disease, or stage IV-NED. Because natural history and prognostic factors for patients with stage IV-NED are poorly determined, we decided to evaluate a group of patients with stage IV-NED treated at a single institution. Patients and methods: Ninety-six patients with isolated recurrence of stage IV breast cancer were analyzed retrospectively. Treatment of loco-regional or distant recurrence was surgery in 18 patients and surgery plus irradiation in 78 patients. Seventy-nine patients received systemic therapy after loco-regional treatment (24 chemotherapy and 55 hormonotherapy). Prognostic factors were analyzed and correlated with disease-free survival (DFS) and overall survival (OS). Results: Five-year DFS and OS for the whole group were 29% and 49% respectively. On the univariate analysis, patients without axillary nodal involvement at the time of mastectomy had significantly greater 5-year DFS and OS than patients with nodal involvement (51% vs. 14% and 70% vs. 34% respectively, p〈 0.05). DFS was also significantly better for patients receiving systemic therapy after local treatment (31% vs. 19%). On the multivariate analysis, absence of nodal involvement and systemic therapy were associated with longer DFS (p = 0.044 and p = 0.008, respectively) and OS (p = 0.009 and p = 0.011, respectively). None of the other factors analyzed including menopausal status, T-stage, number of involved nodes, receptor status, adjuvant therapy, sites of first recurrence, or time from mastectomy to first recurrence had a predictive value for DFS and OS. Conclusion: Patients with stage IV-NED have poor prognosis due to early development of metastatic disease. Absence of axillary nodal involvement at the time of mastectomy and systemic therapy following local management is associated with improved DFS and OS. These results suggest that systemic therapy after local treatment in stage IV-NED is indicated. Poor prognosis in patients with previous nodal involvement warrants new approaches.
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    URL: http://dx.doi.org/10.1023/A:1006090319083
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  • 84
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    Electronic Resource
    Combined effect of vitamin D3 analogs and paclitaxel on the growth of MCF-7 breast cancer cells in vivo (1999)
    Springer
    Breast cancer research and treatment 53 (1999), S. 113-120 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; BNX nude mouse ; paclitaxel ; Vitamin D3 analogs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Vitamin D3 analogs and paclitaxel (Taxol) are able to inhibit the in vitro growth of a variety of malignant cells including breast cancer cells. These two compounds decrease growth by different mechanisms and they have non-overlapping toxicities. We examined the abilities of three vitamin D3 compounds to inhibit growth of a human mammary cancer (MCF-7) in BNX triple immunodeficient mice either alone or with Taxol. Vitamin D3 analogs were 1,25(OH)2D3 (code name, Compound C), 1,25(OH)2-16-ene-23-yne-19-n or-26,27-F6-D3 (Compound LH), and 24a,26a,27a,-trihomo-22,24-diene-1,25(OH)2D3 (EB1089). At the doses chosen, the antitumor effect of vitamin D3 analogs alone was greater than that of Taxol alone, and an additive effect was observed when a vitamin D3 analog and Taxol were administered together. EB1089 was the most potent compound, and the EB1089 plus Taxol was the most active combination, decreasing the tumor mass nearly 4-fold compared to controls. Weight-gain in each of the experimental cohorts at the end of the study was less than the control group, but the gain was significantly less in only two experimental groups (those receiving either EB1089 or Compound C plus Taxol). None of the animals became hypercalcemic, and their complete blood counts, serum electrolyte analyses, and liver and renal functions were all fairly similar and within the normal range. In summary, this combination of a vitamin D3 analog and Taxol has the potential to be a therapy for breast cancer.
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    URL: http://dx.doi.org/10.1023/A:1006123819675
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  • 85
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    Comparative analysis of breast cancer recurrence risk for patients receiving or not receiving adjuvant cyclophosphamide, methotrexate, fluorouracil (CMF). Data supporting the occurrence of ‘cures’ (1999)
    Springer
    Breast cancer research and treatment 53 (1999), S. 209-215 
    Details
    ISSN: 1573-7217
    Keywords: adjuvant chemotherapy ; breast cancer ; cure ; early recurrences ; late recurrences ; recurrence risk pattern
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To comparatively analyse the risk of recurrence at given times after surgery for breast cancer patients receiving or not receiving adjuvant CMF. Patients and methods: A total of 1452 node positive patients, who entered controlled clinical trials carried out at the Milan Cancer Institute and underwent radical or modified radical mastectomy for operable breast cancer, were examined. In 575 cases no further treatment was performed, whereas 877 pts were given 6 or 12 courses of adjuvant Cyclophosphamide, Methotrexate, Fluorouracil (CMF). The recurrence risk was estimated by the event-specific hazard rate for first failure and distant metastases, and, following Efron, hazard rates were fitted by logistic regression models. Results: The hazard rate for first failure and distant metastases showed a double peaked pattern for both treated patients and controls, with a first major peak at about 18–24 months from surgery (early metastases), a second minor peak at the 5th–6th year, and a tapered plateau-like tail extending over 10 years from surgery (late metastases). As expected, the recurrence risk of CMF treated patients was lower than the corresponding risk of patients undergoing surgery only. However, the difference was highly evident for early recurrences, while it declined and disappeared afterwards. Conclusion: Our findings confirm previous reports on patients not receiving adjuvant chemotherapy, suggesting that the recurrence risk for operable breast cancer has a multipeak pattern. As far as CMF treated patients are concerned, the unchanged peak timing together with the early recurrence risk reduction in comparison to controls are much more consistent with the real nonappearance of some early recurrences (putatively ‘cured’ patients) than with the delay in their manifestation. As late relapsing patients seem to have at most marginal benefits from adjuvant CMF, ways to recognize patients doomed to have late recurrence and new ways for treating micrometastases resulting in late recurrences are required.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006134702484
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  • 86
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    Electronic Resource
    Analyzing prognostic factors in breast cancer using a multistate model (1999)
    Springer
    Breast cancer research and treatment 54 (1999), S. 83-89 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; multivariate analysis ; multistate model ; prognostic factors ; risk ; survival analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In breast cancer clinical research, an important goal is to analyze how factors are seen to affect the disease process. Meanwhile, the disease progression is not fully modelled using standard analysis since transitions between intermediate events such as local-regional recurrences (LRR) or metachronous contralateral breast cancer (MCBC) are not considered. In the present study, the progression of disease was modelled using a multistate model. By this approach, we assessed transitions during the course of the disease and studied prognostic factors for each transition. The model was applied to 6,185 patients with unilateral ductal invasive breast cancer, clinical stage I through III, treated between 1981 and 1988 at the Curie Institute. At first diagnosis, high clinical stage, high histological grade, positive lymph nodes, and age less than 40 years were associated with increased risks of LRR, metastases, or death. Except age, the same factors remained predictive for metastases or death following LRR. Chemotherapy for the first cancer was associated with a decreased risk for developing MCBC. As the time interval from diagnosis of the primary tumor to that of a local or contralateral recurrence increased, the risk of metastases or death decreased. Nodal status for the first tumor and clinical stage for the contralateral tumor increased the risk of metastases or death following MCBC. Conversely, the risk decreased for patients who received adjuvant hormone therapy following MCBC. In conclusion, the multistate model offers us a much more appropriate way to study prognostic factors for each transition in breast cancer disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006197524405
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  • 87
    Electronic Resource
    Electronic Resource
    Methodological arguments for the necessity of randomized trials in high-dose chemotherapy for breast cancer (1999)
    Springer
    Breast cancer research and treatment 54 (1999), S. 31-38 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; high-dose chemotherapy ; randomized trials ; stem-cell transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the past ten years high-dose chemotherapy with autologous haematopoetic stem-cell support (HD-CT) has increasingly been used for breast cancer. But the vast majority of trials are small phase I/II studies showing until now not enough evidence that HD-CT is superior to conventional-dose chemotherapy (CD-CT). In contrast to this, the public perception of this treatment is different. Patients as well as physicians often uncritically believe in reports contrasting the positive results obtained in case series treated by HD-CT with those of historical control groups. This leads to the problem that many patients and also clinicians are not willing to participate in randomized trials on this topic. A critical assessment of current knowledge on the effectiveness of HD-CT in breast cancer is given. The problems related to the use of historical controls, in general, and especially in the setting of HD-CT are demonstrated. Using data of patients treated with CD-CT within trials of the German Breast Cancer Study Group (GBSG) it will be shown that results similarly favorable to those reported from patients treated with a high-dose regimen may be produced using quite simple selection mechanisms. Comparisons of patients treated with HD-CT with historical control groups of patients treated with CD-CT may be misleading. A valid treatment comparison is only possible by means of large randomized trials. Clinicians should participate in the ongoing trials and enter all eligible patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006111821492
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  • 88
    Electronic Resource
    Electronic Resource
    Diet and risk for breast cancer recurrence and survival (1999)
    Springer
    Breast cancer research and treatment 53 (1999), S. 241-253 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; diet ; recurrence ; survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Dietary factors may influence the risk for breast cancer and also the prognosis following diagnosis and treatment. The aim of this study was to assess whether self-reported prediagnosis diet or other patient factors associated with breast cancer incidence were predictive of recurrence and survival. Patients (n=149) diagnosed with primary breast cancer between 1989 and 1991 were followed for five or more years. Total energy (hazard ratio (HR)=1.58, 95%, confidence interval (CI)= 1.05, 2.38) as well as total (HR = 1.46, 95% CI = 1.05, 2.01), saturated (HR = 1.79,95% CI = 1.05, 3.04), and monounsaturated (HR = 1.65, 95% CI = 1.09,2.49) fat intakes were associated with increased risk, and energy-adjusted bread and cereal consumption (HR = 0.55, 95% CI = 0.33, 0.93) with decreased risk of recurrence. Both total energy (HR = 1.58, 95% CI = 1.03, 2.43) and polyunsaturated fat (HR = 1.84, 95% CI = 1.09, 3.13) intakes were associated with an increased risk of death. All associations between dietary fat and recurrence and survival attenuated following energy adjustment. Oral contraceptive use (HR = 1.28, 95% CI = 1.03, 1.60), lymph node positive status (HR = 2.36, 95% CI = 1.01, 5.49), and tumor stage (HR = 2.22, 95% CI = 1.02, 4.81) were associated with increased risk of recurrence. Tumor stage (HR = 4.96, 95% CI = 1.86, 13.23), lymph node positive status (HR = 3.31, 95% CI = 1.38, 7.95, and estrogen receptor negative status (HR = 2.46, 95% CI = 1.02, 5.94) were associated with increased risk, and arm muscle circumference (HR = 0.27, 95% CI = 0.09, 0.86) and mammographic utilization (HR = 0.77, 95% CI = 0.61, 0.98) with decreased risk of death. Higher levels of energy, fat intakes, and selected patient characteristics (particularly disease stage and anthropometric indicators of adiposity) appear to increase risk of recurrence and/or shortened survival following the diagnosis of breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006190820231
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  • 89
    Electronic Resource
    Electronic Resource
    Recognition of an epitope of a breast cancer antigen by human antibody (1999)
    Springer
    Breast cancer research and treatment 53 (1999), S. 279-290 
    Details
    ISSN: 1573-7217
    Keywords: human antibody ; antigen epitope ; breast cancer ; peptide ; retinoblastoma binding protein 1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A novel tumor-associated peptide epitope KASIFLK expressed preferentially by breast cancer cells was identified using an IgG antibody from a breast cancer patient. A cDNA library from a MCF-7 breast cancer cell line was screened to isolate three cDNA clones that were immunoreactive with this antibody. KASIFLK was located in clones 27 and 40, both of which were identical to the cDNA and protein sequence of retinoblastoma binding protein 1 (RBP1, 250–256). An affinity-purified IgG antibody against the peptide epitope was completely absorbed by cytoplasmic extracts of MCF-7 cells. Immunohistochemical staining using this antibody revealed the antigen in MCF-7 cells and in 12 of 15 primary breast cancer tissues and 3 of 34 other cancer tissues, but in none of 6 normal breast tissues. Anti-KASIFLK antibody titers were significantly higher in sera of 55 breast cancer patients than in sera from 30 normal healthy donors (P 〉 0.001). These results suggest that KASIFLK or its cross-reactive epitope is a breast cancer antigen and is immunogenic in humans.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006115922401
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  • 90
    Electronic Resource
    Electronic Resource
    Synergistic cooperation between c-Myc and Bcl-2 in lymph node progression of T1 human breast carcinomas (1999)
    Springer
    Breast cancer research and treatment 54 (1999), S. 39-45 
    Details
    ISSN: 1573-7217
    Keywords: apoptosis ; Bcl-2 ; breast cancer ; c-Myc ; metastasis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The overexpression of Bcl-2, an anti-apoptotic oncogene, identifies human T1 breast cancer patients who have an increased risk of lymph-node metastasis. We examined in these patients (n=142) whether the c-Myc oncogene influences metastatic progression in conjunction or not with Bcl-2 expression and the loss of apoptosis in tumors. The association between Bcl-2 and lymph-node metastasis was only significant when c-Myc was concomitantly expressed (χ2 test, p=0.008). Moreover, very large associations (pOR=6.4) between c-Myc and lymph-node metastasis were observed among Bcl-2 positive tumors and tumors with loss of apoptosis (pOR=8.4). In contrast, the metastatic advantage linked to Bcl-2 was decreased (pOR=2) when c-Myc was not coexpressed. It is concluded that the synergism between Bcl-2 and c-Myc oncogenes may promote metastasis in breast tumors, linked to loss of apoptosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006120006471
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  • 91
    Electronic Resource
    Electronic Resource
    Tumor flow in malignant breast tumors measured by Doppler ultrasound: an independent predictor of survival (1999)
    Springer
    Breast cancer research and treatment 54 (1999), S. 65-71 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; blood flow ; Doppler ; prognosis ; ultrasound
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of this study was to investigate tumor blood flow in breast cancers with regard to its impact on the overall survival of patients. Tumor blood flow was assessed in seventy-four patients with primary breast cancer by the use of color-coded Doppler ultrasound techniques. Preoperatively obtained Doppler frequency spectra were analyzed for peak systolic flow velocity (Vmax). Color Doppler signals were detected in 71 (96%) of the breast tumors. Out of 74 patients, 17 experienced a relapse or distant metastasis, and 15 women had died due to breast cancer at the time of data analysis. The mean Vmax of the patients who had died was 0.27 m s−1, whereas survivors showed a mean Vmax of 0.16 m s−1(p=0.01. Vmax, nodal status, and progesterone receptor status remained the only significant factors of overall survival in the multivariate model, whereas tumor size, tumor grade, and estrogen receptor status failed to retain prognostic significance. Moreover, Vmax was identified as the most important prognostic marker for survival in our series. The five-year-survival was 82.3% in Vmax≤ 0.25 m s−1 patients versus 36.6% in women with tumor flow greater than 0.25 m s−1. Patients with Vmax 〉 0.25 m s−1 experienced a 4.33-fold increased risk of death secondary to the underlying disease. In summary, our data showed that tumor blood flow velocity measured by ultrasonography is an independent prognostic factor of survival in breast cancer patients. Furthermore, tumor flow velocity allows identification of patients at very high risk of death due to breast cancer. Large scale clinical trials should evaluate the clinical usefulness and future impact of this procedure for adjuvant treatment decisions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006148812831
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  • 92
    Electronic Resource
    Electronic Resource
    Rural breast cancer treatment: evidence from the Reaching Communities for Cancer Care (REACH) project (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 59-66 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; neoplasm ; recommendations ; rural ; treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. Research shows that rural populations are more likely than their urban counterparts to be diagnosed with late‐stage cancer, but less is known about appropriateness of cancer treatment in rural locations after diagnosis. The objective of this analysis was to assess the degree to which rural breast cancer treatment was received in concordance with national recommendations. Methods. Data came from 251 stage I and II breast cancer patients residing in rural North Carolina. State‐of‐the‐art care was defined using the National Cancer Institute's (NCI) physician data query (PDQ) database, and cases were categorized into appropriate primary and/or adjuvant treatment. Chi‐square and Fishers' exact tests were used to assess changes in appropriate treatment over time (1991–1996) and between stage. Multiple logistic regression was used to determine whether any patient or disease characteristics were associated with receipt of appropriate treatment. Results. Most (81–90%) of the breast cancer cases received the appropriate primary therapy (mastectomy or lumpectomy followed by radiation therapy); of these, the majority received a mastectomy (66–72%). Fewer women received adjuvant therapy as recommended (27–61%), although significantly more stage II than stage I cases did so (p≤0.05). Regression showed that stage and estrogen‐receptor (ER) status were associated with appropriate therapy. Conclusions. The findings suggest that there exist deviations from NCI established treatment recommendations among rural breast cancer patients. More research is needed to develop better methods for dissemination of state‐of‐the‐art cancer information to rural physicians and patients, and to understand how treatment decisions are made.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006279117650
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  • 93
    Electronic Resource
    Electronic Resource
    Randomized trial of diethylstilbestrol vs. tamoxifen in postmenopausal women with metastatic breast cancer. An updated analysis (1999)
    Springer
    Breast cancer research and treatment 54 (1999), S. 117-122 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; diethylstilbestrol ; postmenopausal women ; tamoxifen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract One hundred fifty‐one postmenopausal women with progressive metastatic breast cancer and no prior hormonal therapy were treated with either diethylstilbestrol (DES) or tamoxifen (TAM). One hundred forty‐three eligible patients were followed until death or for a minimum of 14.1 years on the DES arm or 16.7 years on the TAM arm. The overall objective response was 42% for DES and 33% for TAM (p=0.31) and the median duration of response was 11.8 months for DES and 9.9 months for TAM (p=0.38). Duration of response and progression‐free survival were not found to be significantly different between DES and TAM (p=0.32 and 0.65, respectively). The median survival was 3.0 years for DES vs. 2.4 years for TAM. The 5‐year survival was 35% for the DES arm and 16% for the TAM arm. Survival was significantly better for women on DES than for women on TAM (adjusted p=0.039). Review of records did not show any difference in pattern of treatment failure or subsequent treatments in the DES and TAM arms. Treatment with DES was more commonly associated with toxicity such as nausea, edema, vaginal bleeding, and cardiac problems, whereas hot flashes were commonly seen with TAM therapy. The initial treatment with DES is associated with increased survival. The basis of this survival advantage is not known. TAM still is the preferred agent in the treatment of metastatic breast cancer, but this trial underscores the fact that estrogens have activity and remain in the armamentarium for treatment of selected patients with metastatic breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006185805079
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  • 94
    Electronic Resource
    Electronic Resource
    Invasion marker PAI‐1 remains a strong prognostic factor after long‐term follow‐up both for primary breast cancer and following first relapse (1999)
    Springer
    Breast cancer research and treatment 54 (1999), S. 147-157 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; cathepsin D ; PAI‐1 ; prognosis ; S‐phase fraction ; uPA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In 1991, our group was the first to report the prognostic strength of plasminogen activator inhibitor type 1 (PAI‐1) in primary breast cancer. The prognostic impact of invasion markers PAI‐1 and urokinase‐type plasminogen activator (uPA) on disease‐free survival (DFS) and overall survival (OS) in breast cancer has since been independently confirmed. We now report on the prognostic impact of PAI‐1 and uPA after long‐term median follow‐up of 77 months for our cohort (n=316). Levels of uPA, PAI‐1, and cathepsin D were determined in tumor tissue extracts by immunoenzymatic methods. S‐phase fraction (SPF) was measured flowcytometrically in paraffin sections. Using log‐rank statistics, optimized cutoffs were found for PAI‐1 (14 ng/mg), uPA (3 ng/mg), cathepsin D (41 pmol/mg), and SPF (6%). In all patients, various factors (PAI‐1, uPA, nodal status, SPF, cathepsin D, grading, tumor size, hormone receptor status) showed significant univariate impact on DFS. In Cox analysis, only nodal status (p 〈 0.001, RR: 3.1) and PAI‐1 (p 〈 0.001, RR: 2.7) remained significant. In node‐negative patients (n = 147), PAI‐1, uPA, and SPF had significant univariate impact on DFS, whereas in Cox analysis, only PAI‐1 was significant. PAI‐1 was also significant for DFS within subgroups defined by established factors. In CART analysis, uPA enhanced the prognostic value of PAI‐1 and nodal status for determination of a very‐low‐risk subgroup. For OS, only lymph node status and PAI‐1 were significant in multivariate analysis. PAI‐1 levels in the primary tumor were also a significant prognostic marker for survival after first relapse in both univariate and multivariate analysis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006118828278
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  • 95
    Electronic Resource
    Electronic Resource
    Association between endometrial cancer and tamoxifen treatment of breast cancer (1999)
    Springer
    Breast cancer research and treatment 54 (1999), S. 255-260 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; endometrial cancer ; tamoxifen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A retrospective cohort‐study in 4109 breast cancer patients was undertaken to determine how tamoxifen affected the risk of endometrial cancer. Data on 1701 tamoxifen‐treated women were analysed. Two thousand four hundred and eight non‐tamoxifen users served as control group. The occurrence of new primary uterine cancers was assessed by computerized linkage to the Austrian Cancer Registry. Twenty‐five women who subsequently developed endometrial cancer were identified. Eight uterine cancers occurred in the tamoxifen group, whereas 17 uterine cancers were found in the control group. The estimate of the relative risk (RR) showed an increased risk to develop endometrial cancer for the tamoxifen group RR 1.136 (95% CI 0.71; 1.80). Analysis of relevant confounding variables did not show any differences in the two groups. In conclusion, this retrospective study demonstrated a non‐significant increased risk of endometrial cancer in women receiving tamoxifen as treatment for breast cancer. However, the magnitude of RR and the absolute number of endometrial cancer cases in this long term observation demonstrate clearly that the clinical benefit of tamoxifen therapy greatly outweighs the risk.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006126411210
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  • 96
    Electronic Resource
    Electronic Resource
    Tissue inhibitor of metalloprotease (TIMP)‐1 and proliferative behaviour of clonal breast cancer cells (1999)
    Springer
    Breast cancer research and treatment 54 (1999), S. 235-244 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; cell culture ; cell growth ; TIMP‐1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the present paper, we have examined whether human tissue inhibitor of metalloprotease‐1 (hTIMP‐1) is able to exert a growth factor‐like effect on two clonal cell lines (BC‐3A and BC‐61), isolated from a parental line of human breast carcinoma cells (8701‐BC), and endowed with different growth and invasive behaviour ‘in vitro’ and in nude mouse. The data obtained indicate that only the more tumorigenic clonal cell line (BC‐61) is responsive to hTIMP‐1 treatment by increasing its proliferative rate in a dose‐dependent manner. It was also found that BC‐61 cells selectively express a transmembrane protein of about 80 kDa able to bind hTIMP‐1 ‘in vitro’ and ‘in vivo’ with high affinity (Kd of 0.07 ± 0.004   nM), and that treatment of BC‐61 cells with a proliferation‐promoting concentration of hTIMP‐1 is able to stimulate tyrosine‐targeted phosphorylation. The cumulative results obtained strongly support the hypothesis that hTIMP‐1, ‘classically’ regarded as a collagenase inhibitor, may be a crucial element of the extracellular signalling network during breast cancer development by controlling cell growth phenotype in autocrine and paracrine manner, and that intratumoural heterogeneity for the biological response to TIMP‐1 may exist within the composite cell population of the primary tumour site.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006121129382
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  • 97
    Electronic Resource
    Electronic Resource
    Allelic loss of the PTEN region (10q23) in breast carcinomas of poor pathophenotype (1999)
    Springer
    Breast cancer research and treatment 57 (1999), S. 237-243 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; LOH ; polymorphic marker ; poor prognosis ; PTEN
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Loss of heterozygosity (LOH) in loci of the 10q23 region that harbor the PTEN gene and mutations in the sequence of this gene have been found in several primary human tumors including breast carcinomas, suggesting that this gene could be implicated in their pathogenesis. We investigated allelic losses in microsatellites of the 10q23 region, and their correlations with nine pathologic parameters in 105 breast carcinomas. The LOH analysis was performcd by amplifying DNA by PCR, using five markers of the 10q23 region (D10S1687, D10S541, D10S2491, D10S583 and D10S571). LOH in at least one marker of the PTEN region was found in 29.5% of tumors. The statistical comparison between carcinomas with and without LOH in terms of the pathologic parameters showed significant differences in age (p=0.03), lymph node metastases (p=0.02), and higher histological grade (p=0.02); a trend toward significance was found for progesterone receptors (p=0.05). LOH in an individual marker and statistically significant relationships to tumor characteristics were observed at locus D10S541 for lymph node metastases (p=0.04), at D10S2491 (intragenic to the PTEN gene) for lymph node metastases (p=0.02), and at D10S583 for progesterone receptors (p=0.01) and for high grade (p=0.03). These results suggest the PTEN gene, or other genes of the 10q23 region, could be functionally related to breast cancer, probably influencing the development of histological features associated with poor prognosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006273516976
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  • 98
    Electronic Resource
    Electronic Resource
    Insulin‐like growth factor (IGF)‐I rescues breast cancer cells from chemotherapy‐induced cell death – proliferative and anti‐apoptotic effects (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 1-10 
    Details
    ISSN: 1573-7217
    Keywords: apoptosis ; breast cancer ; doxorubicin ; IGF‐I ; paclitaxel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Insulin‐like growth factor (IGF)‐I protects many cell types from apoptosis. As a result, it is possible that IGF‐I‐responsive cancer cells may be resistant to apoptosis‐inducing chemotherapies. Therefore, we examined the effects of IGF‐I on paclitaxel and doxorubicin‐induced apoptosis in the IGF‐I‐responsive breast cancer cell line MCF‐7. Both drugs caused DNA laddering in a dose‐dependent fashion, and IGF‐I reduced the formation of ladders. We next examined the effects of IGF‐I and estradiol on cell survival following drug treatment in monolayer culture. IGF‐I, but not estradiol, increased survival of MCF‐7 cells in the presence of either drug. Cell cycle progression and counting of trypan‐blue stained cells showed that IGF‐I was inducing proliferation in paclitaxel‐treated but not doxorubicin‐treated cells. However, IGF‐I decreased the fraction of apoptotic cells in doxorubicin‐ but not paclitaxel‐treated cells. Recent work has shown that mitogen‐activated protein kinase (MAPK) and phosphotidylinositol‐3 (PI‐3) kinase are activated by IGF‐I in these cells. PI‐3 kinase activation has been linked to anti‐apoptotic functions while MAPK activation is associated with proliferation. We found that IGF‐I rescue of doxorubicin‐induced apoptosis required PI‐3 kinase but not MAPK function, suggesting that IGF‐I inhibited apoptosis. In contrast, IGF‐I rescue of paclitaxel‐induced apoptosis required both PI‐3 kinase and MAPK, suggesting that IGF‐I‐mediated protection was due to enhancement of proliferation. Therefore, IGF‐I attenuated the response of breast cancer cells to doxorubicin and paclitaxel by at least two mechanisms: induction of proliferation and inhibition of apoptosis. Thus, inhibition of IGF‐I action could be a useful adjuvant to cytotoxic chemotherapy in breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006208721167
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  • 99
    Electronic Resource
    Electronic Resource
    Policy guidelines for the utilization of formalin-fixed, paraffin-embedded tissue sections: the UNC SPORE experience (1999)
    Springer
    Breast cancer research and treatment 58 (1999), S. 31-39 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; formalin-fixed paraffin blocks ; policy ; quality control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Paraffin blocks represent a valuable resource that has allowed investigators to apply today's technology to address scientific questions in a shorter period of time and in more diverse populations than would have been possible with fresh or frozen tissue. However, in addition to being an exhaustible resource, there is concern regarding the appropriate use of these tissues, both with respect to medical or legal considerations and quality control and quality assurance practices. We describe policy guidelines to address these concerns, including: safeguards to address medical/legal and patient confidentiality issues, quality control and quality assurance for tissue sectioning, processing and storage, database management for sample tracking, and scientific review for utilization of specimens. These policies and procedures have been developed and implemented by the University of North Carolina (UNC) Specialized Program of Research Excellence (SPORE) in the Breast Cancer Immunohistochemistry (IHC) Core laboratory, in collaboration with our study pathologists, participants, and research investigators. It is our hope that the information and experience described here may stimulate discussion that can ultimately lead to a uniform policy for handling formalin-fixed paraffin-embedded tissues in research.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006354627669
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  • 100
    Electronic Resource
    Electronic Resource
    Short and long‐term effects on survival in breast cancer patients treated by primary chemotherapy: an updated analysis of a randomized trial (1999)
    Springer
    Breast cancer research and treatment 58 (1999), S. 151-156 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; long term effect ; primary chemotherapy ; short term effect ; weighted logrank tests
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A potential advantage of primary over adjuvant chemotherapy in breast cancer survival had been proposed on theoretical grounds. In 1994, early results of the S6‐trial comparing primary chemotherapy vs. adjuvant chemotherapy for operable breast cancer in 390 premenopausal patients had shown significant improvement in survival of the primary chemotherapy arm (p=0.04). An updated analysis conducted in 1995 showed the disappearance of this difference between the two arms (p=0.18). In the present analysis, we investigated the potential short and long‐term benefits attributable to primary chemotherapy by applying weighted logrank tests designed to assess specifically these effects. Results were compared to those obtained with the classical logrank test. At a median follow‐up of 105 months, a significant short‐term survival benefit (p=0.02) in favor of the primary chemotherapy has been shown. However, no long‐term survival benefit (p=0.36) could be documented. The classical logrank test had revealed no significant difference (p=0.24) between the two groups but the proportional hazard assumption being rejected (p=0.04), the efficiency of this test can be questioned. Results using the present analysis suggested that primary chemotherapy delayed early death rates, without significantly modifying long‐term event rates. It emphasizes that a short‐term effect which is not necessarily associated with a long‐term benefit may be seen at an early evaluation and disappear later on.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006339918798
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