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  • 2000-2004  (261)
  • 1920-1924  (1,159)
  • Organic Chemistry  (1,159)
  • breast cancer  (140)
  • MRI  (121)
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  • 101
    Electronic Resource
    Electronic Resource
    Position und Beweglichkeit des Discus articularis nach operativer Versorgung diakapitulärer und hoher Kiefergelenkluxationsfrakturen (2000)
    Springer
    Mund-, Kiefer- und Gesichtschirurgie 4 (2000), S. 111-117 
    Details
    ISSN: 1434-3940
    Keywords: Schlüsselwörter Kiefergelenkfrakturen ; Kernspintomographie ; Achsiographie ; Diskusmobilität ; Diskusposition ; Key words TMJ fractures ; MRI ; Axiography ; Disc mobility ; Disc position
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Magnetic resonance imaging (MRI) assessment of traumatized temporomandibular joints (TMJ) usually focuses on disc position, defining regular joint function by normal, excentric or displaced disc position. So far, there are only few reports regarding disc position after open reduction of diacapitular or high condylar fractures of the TMJ with dislocation. The aim of the present study was to evaluate the role of the disc as regards postoperative functional outcome by electronic axiographic recordings of condylar movements and MRI, displacement of the disc and lesions of TMJ soft tissues being frequent in this type of mandibular fractures. A total of 30 subjects with 37 condylar fractures in whom osteosynthesis was performed using a preauricular approach were imaged postoperatively (mean 24 months) with a 1.5-Tesla MRI system to determine, (a) the position of the disc, (b) the range of mobility of the disc and (c) condylar mobility in closed and open mouth position, comparing fractured sides (FS) vs nonfractured sides (NFS). Linear movements between the two jaw positions in the sagittal plane were measured by superimposing transparencies. The results indicate: (1) more than 70% of the discs (FS) were found to be in normal position; there was no disc displacement without reduction. However, these data stood in contrast to severe limitations of the axiographic tracings as presented by almost 30% of the subjects. (2) Significant correlations were found between fixed (α = 0.05) or highly immobilized (α = 0.01) discs and axiographic limitations, suggesting disc mobility to be a valuable parameter for assessment of the postoperative functional outcome.
    Notes: Zusammenfassung Bei diakapitulären Frakturen bzw. hohen Kollumluxationsfrakturen mit Beziehung zum Lig. laterale sind Verlagerungen des Diskus häufig und werden nach konservativer Therapie mit einer Häufigkeit zwischen 50 und 100% angegeben. Informationen über die Diskusposition nach operativer Versorgung dieser Frakturgruppen liegen bisher nicht vor. Ziel der vorliegenden Studie war es, die Bedeutung von Position und Mobilität des Diskus für das postoperative funktionelle Ergebnis dieser Frakturgruppen zu klären. Die Objektivierung der operativen Ergebnisse bei 30 Patienten mit 37 über einen präaurikulären Zugang versorgten Gelenkfrakturen erfolgte mittels elektronischer Achsiographie und Kernspintomographie (1,5-T-System), im Mittel 24 Monate postoperativ. Erhoben wurden die Position und der Bewegungsumfang des Diskus bzw. des Kondylus im Seitenvergleich. Die linearen Bewegungen zwischen mundoffener und -geschlossener Position wurden durch Folienüberlagerung korrespondierender sagittaler MRT-Schichten ermittelt. Die Ergebnisse zeigten zum einen, dass 〉 70% der Disci auf der Frakturseite orthotop (Position A) lagen und keine fixierten anterioren Dislokationen (C) auftraten. Die achsiographischen Befunde zeigten in Diskrepanz dazu bei immerhin 30% der versorgten Gelenke höhergradige Limitationen der Exkursionsbahnen. Zum anderen bestehen signifikante Zusammenhänge zwischen fixierten (α = 0,05) bzw. hochgradig immobilisierten (α = 0,01) Disken und achsiographisch erfassten Limitationen der Translationsbewegung. Im Gegensatz zu bisherigen Studien sollten nach der operativen Versorgung von Gelenkfrakturen nicht nur die (statische) Diskusposition, sondern in erster Linie die Diskusmobilität als Parameter für das funktionelle Ergebnis berücksichtigt werden.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s100060050181
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  • 102
    Electronic Resource
    Electronic Resource
    Morphological and functional imaging studies on the diagnosis and progression of Parkinson’s disease (2000)
    Springer
    Journal of neurology 247 (2000), S. II11 
    Details
    ISSN: 1432-1459
    Keywords: Key Words Diagnosis ; MRI ; MRS ; Parkinson’s disease ; SPECT ; PET
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This paper reviews the relative abilities of magnetic resonance imaging (MRI), positron emission tomography (PET), single photon emission tomography (SPECT), and proton magnetic resonance spectroscopy (MRS) to detect Parkinson’s disease and monitor its progression. Currently, the main role of MRI lies in its ability to discriminate atypical syndromes from Parkinson’s disease; however, new volumetric approaches may soon allow progression of nigral degeneration to be followed. Proton MRS can also detect reduced levels of putamen N-acetyl aspartate (NAA) in many patients with atypical parkinsonian syndromes. PET and SPECT are both sensitive means of detecting the presence of impaired dopamine terminal function in the striatum and following its progression. PET currently has the greater spatial resolution and provides the added advantages that it also allows extra-striatal dopaminergic function to be monitored.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00007755
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  • 103
    Electronic Resource
    Electronic Resource
    Combination chemotherapy with navelbine and continuous infusion of 5-fluorouracil in metastatic, chemotherapy refractory breast cancer (2000)
    Springer
    Annals of oncology 11 (2000), S. 1041-1043 
    Details
    ISSN: 1569-8041
    Keywords: 5-FU ; breast cancer ; metastatic ; navelbine ; protracted continuous infusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:The protracted continuous infusion (PCI) of5-fluorouracil (5-FU) has proven in several studies an active and welltolerated treatment for advanced, pretreated breast cancer. Navelbine has alsoactivity in this setting. Patients and methods:Heavily pretreated patients with metastaticbreast carcinoma were eligible for the study. Treatment consisted of 5-FU 250mg/m2 given as a PCI by an elastomeric pump and navelbine 20mg/m2 on days 1 and 8, every four weeks. Eighty-three patients(median age 54 years; range 32–82 years) entered the study. The mediannumber of metastatic tumour sites was 2, with visceral involvement in 56patients. Apart from five patients with contraindications, all patients hadbeen pretreated with anthracyclines. Thirty-one patients had received taxanesand seventy-four bolus 5-FU. Results:A median of 5 cycles (range 1–14) per patient wasadministered. The median duration of 5-FU infusion was 17 weeks (range, 4-90).In the 80 evaluable patients (3 not yet evaluable) 12 complete remissions and24 partial remissions occurred (response rate, 45%). Median durationof response was 9 months. Toxicity was mild. Median survival was 20 months. Conclusions:PCI–5-FU combined with navelbine offers areasonable chance of tumour regression with modest side effects in patientswith heavily pretreated breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008333327500
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  • 104
    Electronic Resource
    Electronic Resource
    Weekly docetaxel plus gemcitabine or vinorelbine in refractory advanced breast cancer patients: A parallel dose-finding study (2000)
    Springer
    Annals of oncology 11 (2000), S. 367-371 
    Details
    ISSN: 1569-8041
    Keywords: docetaxel + gemcitabine ; docetaxel + vinorelbine ; phase I ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose:The objective of this study was to determine thedocetaxel MTD when combined with gemcitabine or vinorelbine in advanced breastcancer patients who had received previous anthracycline-based chemotherapy foradvanced disease. Patients and methods:Advanced breast cancer patients aged between18 and 70 with ECOG PS 0–2 who had not responded to, or had relapsedafter, first-line anthracycline-based chemotherapy, were randomized to receiveeither gemcitabine 1000 mg/m2 or vinorelbine 25 mg/m2in combination with escalating doses of docetaxel (starting from 30mg/m2), all on days 1 and 8 every three weeks. Escalation wasstopped if 〉33% of patients treated at a given dose level showed DLTat the first cycle. Results:A total of 34 patients with locally advanced (8) ormetastatic disease (26) were treated, for a total of 94 cycles delivered.Nineteen patients received docetaxel in combination with gemcitabine and 15with vinorelbine. All patients had been pretreated with anthracyclines, and24 of 34 had also received weekly dose-dense paclitaxel. A docetaxel dose of40/m2 proved to be safe when combined on days 1 and 8 withgemcitabine, while a dose of 35 mg/m2 was tolerated in combinationwith vinorelbine. Overall, nine episodes of DLT, all of them neutropenia,occurred at the first cycle. Considering all 94 cyles, grades 3 or 4neutropenia and thrombocytopenia occurred in 15 (44%), and 7(20%) patients. Non-hematologic toxicity was mild, except for threecases of grade 2 peripheral neuropathy. All patients were assessed forresponse on an 'intent-to-treat' basis. Overall, five partial responses wererecorded (docetaxel + gemcitabine = 3 and docetaxel + vinorelbine = 2), fora 15% (95% CI: 5%–31%) overall responserate. Only 1 of 24 (4%) patients who had received weekly dose-densepaclitaxel responded to treatment. Conclusions:The weekly docetaxel administration in combinationwith either gemcitabine or vinorelbine is a well-tolerated treatment forheavily pretreated advanced breast cancer patients. This approach, althoughsometimes capable of achieving a major response, does not seem advisable inadvanced breast cancer patients refractory to both anthracyclines andpaclitaxel.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008346708604
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  • 105
    Electronic Resource
    Electronic Resource
    Bildgebende Diagnostik des Schultergelenks (2000)
    Springer
    Trauma und Berufskrankheit 2 (2000), S. 249-254 
    Details
    ISSN: 1436-6274
    Keywords: Schlüsselwörter ; Schultergelenk ; Basisdiagnostik ; Röntgendiagnostik ; Sonographie ; Computertomographie ; Kernspintomographie ; Arthrographie ; Keywords ; Shoulder joint ; Basic diagnosis ; X-rays ; Sonography ; Computed tomography ; MRI ; Arthrography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: It is its ball-and-socket anatomy that makes the shoulder joint the most flexible of all human joints. This high degree of freedom of movement means, however, on the one hand that early degenerative damage is likely to occur as a result of sports and occupational strains and on the other that it is particularly vulnerable to injuries. Diagnostic radiology from two different perspectives is the basic diagnostic procedure for unexplained shoulder pain and for shoulder injuries. Dislocating osseous injuries or luxations can be detected most precisely or assessed most reliably during follow-up by this means. Intra-articular findings and alterations to the soft tissues (degenerative, traumatic) can be delineated by sonography, computed tomography and magnetic resonance imaging, albeit with differing degrees of reliability and specificity. Sonography is generally available, but not reliably standardized. Computed tomography is the method of choice for diagnosis of osseous and joint injuries. Over the last 10 years magnetic resonance imaging (MRI) has improved in sensitivity and specificity with technical progress (coils, sequences, reconstruction modalities) and has therefore moved into the focus of clinical interest.
    Notes: Das Schultergelenk ist infolge seiner anatomischen Ausbildung als Kugelgelenk das beweglichste Gelenk des menschlichen Körpers. Die sich hieraus ergebenden Bewegungsmöglichkeiten bedingen einerseits bereits frühzeitig degenerative Schädigungen infolge beruflicher oder sportlicher Belastungen und andererseits eine besondere ¶Angriffsfläche für Verletzungen. Die Basisdiagnostik sowohl des unklaren Schulterschmerzes als auch verletzungsbedingter Schädigungen am Schultergelenk ist die Röntgendiagnostik in 2 Ebenen. Dislozierende ossäre Verletzungen bzw. Luxationen sind hiermit treffsicher nachzuweisen bzw. in der Verlaufskontrolle zu beurteilen. Intraartikuläre Befunde und Weichteilveränderungen (degenerativ, traumatisch) sind hingegen mit den Schnittbildverfahren der Sonographie, Computertomographie und Kernspintomographie mit unterschiedlicher Treffsicherheit und Spezifität nachzuweisen. Die klassische Gelenkarthrographie hingegen tritt gegenüber diesen Verfahren deutlich in ihrer Bedeutung zurück. Die Sonographie ist ein ubiquitär verfügbares, jedoch wenig standardisiertes Verfahren. Die Reproduzierbarkeit der Befunde ist fraglich. Die Computertomographie stellt die Methode der Wahl bei der Diagnostik von okkulten ossären bzw. Gelenkverletzungen dar. Die Methode ist breit verfügbar und mit vertretbarem Aufwand durchzuführen. In den letzten 10 Jahren hat die Kernspintomographie infolge der technischen Weiterentwicklung (Spulen, Sequenzen, Rekonstruktionsmöglichkeiten usw.) an Sensitivität und Spezifität gewonnen. In der Summe aller klinischen Fragestellungen stellt sie neben der Basisdiagnostik derzeit die effektivste Untersuchungsmethode des Schultergelenks dar.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s100399900176
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  • 106
    Electronic Resource
    Electronic Resource
    Dose-finding study of oral idarubicin and cyclophosphamide in first-line treatment of elderly patients with metastatic breast cancer (2000)
    Springer
    Annals of oncology 11 (2000), S. 229-230 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; cyclophosphamide ; elderly ; idarubicin ; oral chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008384820279
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  • 107
    Electronic Resource
    Electronic Resource
    A feasibility study evaluating docetaxel-based sequential and combination regimens in the adjuvant therapy of node-positive breast cancer (2000)
    Springer
    Annals of oncology 11 (2000), S. 169-175 
    Details
    ISSN: 1569-8041
    Keywords: adjuvant therapy ; breast cancer ; docetaxel ; feasibility
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background and purpose:Docetaxel is an active agent in thetreatment of metastatic breast cancer. We evaluated the feasibility ofdocetaxel-based sequential and combination regimens as adjuvant therapies forpatients with node-positive breast cancer. Patients and methods:Three consecutive groups of patients withnode-positive breast cancer or locally-advanced disease, aged ≤70 years,received one of the following regimens: a) sequential A → T → CMF:doxorubicin 75 mg/m2 q 3 weeks × 3, followed by docetaxel 100mg/m2 q 3 weeks × 3, followed by i.v. CMF days 1 + 8 q 4weeks × 3; b) sequential accelerated A → T → CMF: A and T wereadministered at the same doses q 2 weeks; c) combination therapy: doxorubicin50 mg/m2 + docetaxel 75 mg/m2 q 3 weeks × 4,followed by CMF × 4. When indicated, radiotherapy was administeredduring or after CMF, and tamoxifen started after the end of CMF. Results:Seventy-nine patients have been treated. Median age was48 years. A 30% rate of early treatment discontinuation was observedin patients receiving the sequential accelerated therapy (23% duringA → T), due principally to severe skin toxicity. Median relativedose-intensity was 100% in the three treatment arms. The incidence ofG3–G4 major toxicities by treated patients, was as follows: skintoxicity a: 5%; b: 27%; c: 0%; stomatitis a: 20%;b: 20%; c: 3%. The incidence of neutropenic fever was a:30%; b: 13%; c: 48%. After a median follow-up of 18months, no late toxicity has been reported. Conclusions:The accelerated sequential A → T → CMFtreatment is not feasible due to an excess of skin toxicity. The sequentialnon accelerated and the combination regimens are feasible and under evaluationin a phase III trial of adjuvant therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008345432342
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  • 108
    Electronic Resource
    Electronic Resource
    The contribution of molecular markers to the prediction of response in the treatment of breast cancer: A review of the literature on HER-2, p53and BCL-2 (2000)
    Springer
    Annals of oncology 11 (2000), S. 647-663 
    Details
    ISSN: 1569-8041
    Keywords: BCL-2 ; breast cancer ; HER-2 ; p53 ; predictive factor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:The selection of therapies for breast cancer is todaybased on prognostic features (chemotherapy, radiotherapy), hormone receptorstatus (hormonal therapy) and HER-2 status (trastuzumab therapy). HER-2,p53and BCL-2are tumour-related proteins that have thepotential to further improve individualisation of patient management, bypredicting response to chemotherapy, hormonal therapy and radiotherapy. Materials and methods:This paper reviews the rationale for theuse of these proteins as predictive factors, as well as the publishedliterature addressing the use of each one to predict response to hormonaltherapy, chemotherapy and radiotherapy. Results:HER-2, p53and BCL-2remaininadequately assessed as predictive factors in breast cancer. HER-2 evaluationis required for the selection of patients for trastuzumab (Herceptin®)therapy, as trials of this therapy have been limited to HER-2 overexpressors.HER-2 overexpression may be predictive of resistance to hormonal therapy.Anthracyclines are effective therapy for breast cancer regardless of HER-2status, but patients whose tumours overexpress HER-2 appear to receive thegreatest relative benefit from this therapy. Studies of HER-2 as a predictorof response to CMF and to radiotherapy are inconclusive at this time. No datayet exist to support the use of p53or BCL-2as predictivefactors in the therapy of breast cancer. Conclusions:At this point in time, there is inadequate evidenceto support the use of HER-2, p53or BCL-2to guide theselection of hormonal therapy, chemotherapy or radiotherapy for breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008390429428
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  • 109
    Electronic Resource
    Electronic Resource
    Activity and toxicity of GI147211 in breast, colorectal and non-small-cell lung cancer patients: An EORTC–ECSG phase II clinical study (2000)
    Springer
    Annals of oncology 11 (2000), S. 793-797 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; camptothecins ; colorectal cancer ; GI147211 ; non-small-cell lung cancer ; topoisomerase I
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:GI147211 is a water-soluble synthetic analogue ofcamptothecin showing promising in vivoand in vitroantitumor activity and an acceptable toxicity profile. Patients and methods:Between April 1995 and November 1996, 67eligible patients with pretreated breast cancer (25 patients) andchemo-naïve colorectal (19 patients) and non-small-cell lung cancer (23patients) were entered into three multicentric, non-randomized phase IItrials. Treatment schedule consisted of intravenous GI147211 administered ata dose of 1.2 mg/m2/day for five consecutive days every threeweeks. Results:Hematological toxicity was common with grade 3–4neutropenia in 54% of patients and neutropenic fever together or notassociated with infection in 14.5% of patients. Grade 3–4thrombocytopenia and grade 2–4 anemia were observed in 20% andin 68% of patients, respectively. Non-hematological toxicity wasgenerally mild to moderate and consisted mainly of gastrointestinal toxicity,asthenia and alopecia. A dose-escalation to 1.5 mg/m2/d wasfeasible in 17 (25%) patients. The antitumor activity of GI147211 wasmoderate in breast cancer patients (3 partial responses (PRs), response rate(RR) 13%) and minimal in non-small cell lung cancer patients (2 PRs,RR 9%). No objective responses were obtained in colorectal patients. Conclusions:GI147211, at the dose and schedule employed in thisstudy, showed an acceptable safety profile but a modest antitumor activity inthe examined tumor types.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008373031714
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  • 110
    Electronic Resource
    Electronic Resource
    Front-line treatment of advanced breast cancer with docetaxel and epirubicin: A multicenter phase II study (2000)
    Springer
    Annals of oncology 11 (2000), S. 1249-1254 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; docetaxel ; epirubicin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose:In a previous phase I trial we evaluated the toxicity anddetermined the maximum tolerated doses of the docetaxel (D)–epirubicin(Epi) combination. We conducted a multicenter phase II study to evaluate theefficacy and tolerability of this regimen as front-line treatment in womenwith advanced breast cancer (ABC). Patients and methods:Fifty-four women with ABC stage IIIB (4patients) or IV (50 patients) received front-line treatment with Epi 70mg/m2 on day 1 and D 90 mg/m2 on day 2. The median agewas 55 years, performance status (WHO) was 0–1 in 49 patients andvisceral disease was present in 45 (83%). Results:All patients were evaluable for toxicity and 50 forresponse. In an intent-to-treat analysis complete remission was observed in5(9%) patients, partial remission in 31 (57%) (overall responserate 66%, 95% confidence interval: 54%–79%),stable disease in 9 (17%) and disease progression in 9 (17%).After a median follow-up of 11.5 months, the median duration of responses was8 months, the median time to disease progression 11.5 months and the mediansurvival has not yet been reached. The probability of one-year survival was65%. Three hundred six cycles of treatment were administered (median6 cycles per patient). Grade 3 and 4 neutropenia was observed in 8(15%) and 31 (57%) patients, respectively, and febrileneutropenia in 19 (35%). Prophylactic rh-G-CSF was used in 45(83%) patients or 226 (74%) cycles. Other hematologic ornon-hematologic toxicities were usually mild. In five (9%) patients theleft ventricular ejection fraction (LVEF) was decreased by more than10% with the treatment. Two patients died during the treatment ofrespiratory failure without associated neutropenia. Conclusions:The combination of docetaxel–epirubicin is aneffective and well tolerated front-line treatment in patients with ABC.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008351310818
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  • 111
    Electronic Resource
    Electronic Resource
    Paclitaxel plus vinorelbine: An active regimen in metastatic breast cancer patients with prior anthracycline exposure (2000)
    Springer
    Annals of oncology 11 (2000), S. 85-89 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; combination therapy ; paclitaxel ; vinorelbine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose:To evaluate the anti-tumour activity and tolerance of thecombination of paclitaxel plus vinorelbine in metastatic breast cancer (MBC)patients previously treated with anthracyclines. Patients and methods:Fifty-six MBC patients who have had at leastone previous anthracycline-containing chemotherapy regimen were enrolled inthis phase II trial. Patients received paclitaxel (135 mg/m2 overone-hour infusion) and vinorelbine (30 mg/m2) both on day 1 of eachthree-week course of therapy (maximum eight courses or until diseaseprogression was evident). Results:Six complete and nineteen partial responses were observedamong the fifty-four assessable patients (response rate of 46%,95% CI: 33%–60%). Responses were observed in alldisease sites and in all subsets of patients. The response rates whenpaclitaxel plus vinorelbine were used as first, second and third-linechemotherapy for metastases were 67%, 41% and 35%,respectively. The response rate among anthracycline-refractory patients was46% (6 of 13). Median time to progression in the overall patient groupwas 28 weeks. The main toxicities (CTC grade 2 or more) were alopecia,myelosuppression and peripheral neuropathy (85%, 46% and19% of patients, respectively). Nine patients (17%) hadneutropenic fever in fifteen of the three hundred twenty-eight coursesadministered (5%). Conclusions:The combination of paclitaxel and vinorelbine on day1 every three weeks is active in MBC patients with prior anthracyclineexposure. The regimen is safe, well tolerated and convenient for the patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008374425246
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  • 112
    Electronic Resource
    Electronic Resource
    Early secondary acute myelogenous leukemia in breast cancer patients after treatment with mitoxantrone, cyclophosphamide, fluorouracil and radiation therapy (2000)
    Springer
    Annals of oncology 11 (2000), S. 1289-1294 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; cyclophosphamide ; fluorouracil ; mitoxantrone ; radiation therapy ; secondary leukemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:The topoisomerase II-targeted drugs,epipodophyllotoxins and anthracyclines, have been shown to inducetherapy-related AML (t-AML) characterized by a short latency period afterchemotherapy, the absence of prior myelodysplastic syndrome and stereotypedchromosome aberrations. Few reports have been published on patients treatedwith the anthracenedione mitoxantrone which also targets topoisomerase II. Weobserved 10 cases of such t-AML over a 7-year-period in breast cancer patientstreated with mitoxantrone combined with fluorouracil, cyclophosphamide andregional radiotherapy, and in three cases with vindesine. Patients and methods:We retrospectively analyzed patientsreferred to our hospital for AML with a past history of polychemotherapy forbreast cancer, including mitoxantrone, either as adjuvant (8patients)/neoadjuvant (1 patient) therapy or for metastatic disease (1patient). We studied the probability of developing t-AML in a prospectiveseries of 350 patients treated with an adjuvant FNC regimen (mitoxantrone,fluorouracil, cyclophosphamide) and radiation therapy. Results:The median age was 45 years (range 35–67). t-AMLdeveloped 13–36 months (median 16) after beginning chemotherapy forbreast cancer, and 4–28 months (median 10.5) after ending treatment. Asdescribed in t-AML following treatment with epipodophyllotoxins oranthracyclines, we found a majority of FAB M4, M5 and M3 phenotypes (7 of 10),and characteristic karyotype abnormalities that also can be found in denovoAML: breakpoint on chromosome 11q23 (3 patients), inv(16)(p13q22)(2 patients), t(15;17)(q22;q11) (1 patient), t(8;21)(q22;q22) (1 patient) anddel(20q)(q11) (1 patient). The prognosis was poor. All patients died of AMLshortly after diagnosis. Since two patients had been enrolled in a prospectivetrial for the treatment of breast cancer which included 350 patients, theprobability of developing t-AML was calculated to be 0.7% from25–40 months, using the Kaplan–Meier method (95% confidenceinterval (95% CI): 0.1–4.5). Conclusions:The combination of mitoxantrone withcyclophosphamide, fluorouracil, and radiation therapy can induce t-AML, aswith other topoisomerase II-targeted drugs. Despite a low incidence, theprognosis appears to be poor.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008375016038
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  • 113
    Electronic Resource
    Electronic Resource
    Breast cancer in women ≤35 years: Review of 1002 cases from a single institution (2000)
    Springer
    Annals of oncology 11 (2000), S. 1255-1262 
    Details
    ISSN: 1569-8041
    Keywords: age ≤35 years ; breast cancer ; single institution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Early-onset breast cancer may differ with respect toetiology, clinical features and outcome compared with breast cancer in olderwomen. To gain further insight, we retrospectively reviewed the clinicalfeatures and outcome of women ≤35 years with primary breast cancer seen atour institution over a 30-year period. Patients and methods:Charts were reviewed for women with operablebreast cancer diagnosed ≤35 years of age seen at the Princess MargaretHospital (PMH), Toronto from 1965–1994. Results:One thousand eighty-six women with non-metastaticinvasive breast cancer, aged 18.3–35.6 years (median 32.1 years) werereferred to PMH. Symptoms at presentation included: self-detected breast lump(83%), other breast symptom (10%), physician diagnosis(4%) and unknown (3%). Tumor size was known in 936 (〉2 cm in61%) and nodal status in 888 (lymph node positive in 52%).Modified radical mastectomy was performed in 568 (57%) andbreast-conservation surgery (BCS) in 422 (42%). Five hundred sixteen(51%) patients received adjuvant radiotherapy and five hundredthirty-four (53%) adjuvant systemic therapy. Two hundred ninety-three(29%) patients had a family history of breast cancer (FH).Contralateral breast cancer (CBC) occurred more frequently in women with FH(Prange 0.042–0.008). Local recurrence (LR) was 37% and73% at 10 years in those treated by BCS with and without radiotherapy,respectively. At 10 years, disease-free survival (DFS) was 30% andoverall patient survival 48%. Conclusions:In this cohort, breast cancer was usuallyself-diagnosed and tumors were 〉2 cm at presentation in approximatelytwo-thirds of cases, suggesting the possibilities of a delay in diagnosis,more aggressive tumors or both. Our results are compatible with the knownassociation of breast cancer FH with increased CBC. Our data also corroboratesthe suggestion that positive genetic testing in this age group should lead toconsideration of more aggressive ipsilateral and contralateral breastmanagement. In those receiving adjuvant irradiation after BCS, the LR rate washigh, but did not impact on overall survival.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008391401404
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    Gemcitabine and vinorelbine in pretreated advanced breast cancer: A pilot study (2000)
    Springer
    Annals of oncology 11 (2000), S. 495-496 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; gemcitabine ; metastases ; vinorelbine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose:Gemcitabine (GEM) and vinorelbine (VNR) are both activeagainst advanced breast cancer (ABC), being able to induce a median ORR of25% and 40%, respectively. Because of their different mechanismof action and good tolerability, the combination of GEM and VNR has beentested in ABC. Patients and methods:Twenty-nine ABC patients pretreated withanthracycline-taxane were treated with GEM 1000 mg/m2 on day 1, 8,15, and VNR 25 mg/m2 on day 1 and 8 every twenty-eight days.Analysis of toxicity pattern, response rate, TTP and OS were carried out. Results:Twenty-nine patients were enrolled into the trial. TheORR was 48% (95% CI: 29–67): a CR was observed in threepatients (10%; 95% CI: 2–27), while eleven patients(38%; 95 CI: 21–58) achieved PR, eight (28%) had a SD, andseven (24%) progressed. Toxicity was mainly hematological and included:grade 3 leukopenia in 48% of cases without episodes of neutropenicfever, grade 3–4 thrombocytopenia in 10%, and grade 2 anemia in7%. Non-hematological toxicities were mild and rather infrequent. Conclusions:The GEM–VNR combination seems to be active inpretreated ABC with an acceptable toxicity pattern, and may well reppresentan interesting therapeutic choice after anthracycline/taxane regimens.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008348704373
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  • 115
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    Psychosocial predictors of survival: Metastatic breast cancer (2000)
    Springer
    Annals of oncology 11 (2000), S. 469-474 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; Prognostic factors ; psychosocial factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Research interest in psychosocial predictors of theonset and course of cancer has been active since the 1950s. Recently wereported associations between psychological factors and survival in patientswith metastatic melanoma. We now report a replication of this study in asample of women with metastatic breast cancer. Patients and methods:Ninety-nine patients with metastatic breastcancer completed questionnaires measuring cognitive appraisal of threat,coping, psychological adjustment, perceived aim of treatment, social supportand quality of life, approximately four months after diagnosis. Survival wasmeasured from date of study entry to date of death or censored at the date oflast follow-up for surviving patients. Results:In a multivariate analysis, four factors independentlypredicted outcome. Patients with metastases in the liver, lung or pleurasurvived for a shorter duration (P 〈 0.001); older patients(P 〈 0.001) and those with a better appetite (P 〈0.05) also lived for a shorter time. Patients who minimised the impact ofcancer survived longer (a median of 29.1 vs. 23.9 months after study entry,P 〈 0.01). Conclusions:Minimisation was also significantly associated withoutcome in patients with metastatic melanoma who participated in anidentically designed study, reported elsewhere. This suggests thatminimisation may have a general impact on cancer progression and deservescloser scrutiny in other cancers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008396330433
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  • 116
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    Primary node negative breast cancer in BRCA1 mutation carriers has a poor outcome (2000)
    Springer
    Annals of oncology 11 (2000), S. 307-313 
    Details
    ISSN: 1569-8041
    Keywords: BRCA1 ; breast cancer ; p53 ; survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:The association between BRCA1 germ-linemutations and breast cancer prognosis is controversial. A historical cohortstudy was designed to determine the prognosis for women with axillary lymphnode negative hereditary breast cancer. Patients and methods:We tested pathology blocks from 118Ashkenazi Jewish women with axillary lymph node negative breast cancer for thepresence of the two common BRCA1 founder mutations, 185delAG and5382insC. Patients were followed up for a median of 76 months. SomaticTP53mutations were screened for by immunohistochemistry, and directsequencing was performed in the BRCA1-positive tumours. Results:Sixteen breast cancer blocks (13.6%) carried aBRCA1 mutation. Young age of onset, high nuclear grade, negativeestrogen receptor status and over-expression of p53 were highly associatedwith BRCA1-positive status (P-values all 〈0.01).BRCA1 mutation carriers had a higher mortality than non-carriers(five-year overall survival, 50% and 89.6%, respectively,P = 0.0001). Young age of onset, estrogen receptor negative status,nuclear grade 3, and over-expression of p53 also predicted a poor outcome. Coxmultivariate analyses showed that only germ-line BRCA1 mutationstatus was an independent prognostic factor for overall survival (P= 0.01). Among nuclear grade 3 tumours, the BRCA1 mutation carrierstatus was a significant prognostic factor of death (risk ratio 5.8,95% confidence interval: 1.5–22, P = 0.009). Sequencingof BRCA1-related breast cancers revealed one TP53missensemutation not previously reported in breast cancer. Conclusions:Using a historical cohort approach, we haveidentified BRCA1 mutation status as an independent prognostic factorfor node negative breast cancer among the Ashkenazi Jewish women. Thosemanaging women carrying a BRCA1 mutation may need take these findingsinto consideration. Additionally, our preliminary results, taken together withthe work of others suggest a different carcinogenic pathway inBRCA1-related breast cancer, compared to non-hereditary cases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008340723974
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  • 117
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    Mannose 6-Phosphate/Insulin-Like Growth Factor 2 Receptor, a Bona Fide Tumor Suppressor Gene or Just a Promising Candidate? (2000)
    Springer
    Journal of mammary gland biology and neoplasia 5 (2000), S. 85-94 
    Details
    ISSN: 1573-7039
    Keywords: Mannose 6-phosphate/insulin-like growth factor 2 receptor ; tumor suppressor gene ; breast cancer ; loss of heterozygosity ; somatic mutation ; microsatellite instability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R)3 is considereda “candidate” tumor suppressor gene. This hypothesis has been provoked by the identificationof loss of heterozygosity (LOH) at the M6P/IGF2R locus on chromosome 6q26 in breast andliver cancer, accompanied by point mutations in the remaining allele. Somatic mutations incoding region microsatellites have also been described in replication error positive (RER+)tumors of the gastrointestinal tract, endometrium and brain. These genetic data are compelling,but a tumor suppressor gene candidate has to meet functional as well as genetic criteria. Thisreview weighs the evidence and discusses the observations that are necessary to promoteM6P/IGF2R from candidate to bona fide tumor suppressor gene.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009571417429
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  • 118
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    Rat Models of Premalignant Breast Disease (2000)
    Springer
    Journal of mammary gland biology and neoplasia 5 (2000), S. 409-420 
    Details
    ISSN: 1573-7039
    Keywords: Pre-malignancy ; breast cancer ; experimental model ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract While a number of agents have been shown to induce mammary carcinogenesis in the rat, premalignant stages of the disease have been best characterized in chemically-induced models, specifically those initiated by either 7,12 dimethylbenz[α]anthracene (DMBA)4 or 1-methyl-1-nitrosourea (MNU). In general, it appears that epithelial cells in mammary terminal end buds or terminal ductules are the targets of carcinogenic initiation, and that a series of morphologically identifiable steps are involved in the development of mammary carcinoma. The premalignant steps include ductal hyperplasia of the usual type and carcinoma in situ of the cribriform or comedo type; atypical ductal hyperplasia has not been reported. Thus the histogenesis of lesions occurring in chemically induced mammary carcinogenesis in the rat is similar to that observed in the human; although, the spectrum of lesions observed in the rat is limited. Opportunities to investigate the biological and molecular characteristics of premalignant breast disease in the rat are presented.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009582012493
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  • 119
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    Estrogen Metabolism as a Regulator of Estrogen Action in the Mammary Gland (2000)
    Springer
    Journal of mammary gland biology and neoplasia 5 (2000), S. 259-270 
    Details
    ISSN: 1573-7039
    Keywords: estrogens ; 17β-hydroxysteroid dehydrogenase (17HSD) ; mammary gland ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Estrogen action in the target cells is dependent on estrogen receptor activity and intracellular estrogen concentration, which, in turn, is affected by the serum concentration and local metabolism in these cells. During the reproductive years the main source of estrogens is the ovarian follicles, but in postmenopausal women most of the estrogens are formed in peripheral tissues. 17β-hydroxysteroid dehydrogenases (17HSDs)6 catalyze the reaction between 17β-hydroxysteroids and 17-ketosteroids, and several distinct 17HSD isoenzymes have been characterized. 17HSD type 1 catalyzes the reaction from low-activity estrone to high-activity estradiol. The type 2 enzyme has an opposite activity, thereby reducing the exposure of tissues to estrogen action. 17HSD type 1 is expressed both in steroidogenic tissues and in the target tissues of steroid action, such as normal and malignant breast tissue, where it may be responsible for maintaining the high intracellular estradiol concentration seen in breast cancer specimens. Therefore, 17HSD type 1 inhibitors may be useful in the treatment and/or prevention of estrogen-dependent malignancies, such as breast cancer. This article deals mainly with 17HSD types 1 and 2 and their role in estrogen action in breast tissue.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009542710520
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  • 120
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    Estrogen Receptor Alpha in Human Breast Cancer: Occurrence and Significance (2000)
    Springer
    Journal of mammary gland biology and neoplasia 5 (2000), S. 271-281 
    Details
    ISSN: 1573-7039
    Keywords: breast cancer ; estrogen receptor ; endocrine therapies ; resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Estrogens have long been recognized as being important for stimulating the growth of a large proportion of breast cancers. Now it is recognized that estrogen action is mediated by two receptors, and the presence of estrogen receptor α (ERα)3 correlates with better prognosis and the likelihood of response to hormonal therapy. Over half of all breast cancers overexpress ERα and around 70% of these respond to anti-estrogen (for example tamoxifen) therapy. In addition, the presence of elevated levels of ERα in benign breast epithelium appears to indicate an increased risk of breast cancer, suggesting a role for ERα in breast cancer initiation, as well as progression. However, a proportion of ERα-positive tumors does not respond to endocrine therapy and the majority of those that do respond eventually become resistant. Most resistant tumors remain ERα-positive and frequently respond to alternative endocrine treatment, indicative of a continued role for ERα in breast cancer cell proliferation. The problem of resistance has resulted in the search for and the development of diverse hormonal therapies designed to inhibit ERα action, while research on the mechanisms which underlie resistance has shed light on the cellular mechanisms, other than ligand binding, which control ERα function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009594727358
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  • 121
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    Historical and Epidemiologic Background of Human Premalignant Breast Disease (2000)
    Springer
    Journal of mammary gland biology and neoplasia 5 (2000), S. 341-349 
    Details
    ISSN: 1573-7039
    Keywords: Premalignancy ; risk ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Premalignant breast disease in humans is a concept that admits to a broad range of elements and possible determinants predicting the likelihood of developing breast cancer. Most of these elements are relative, such as the risk of breast cancer for women that is 130 times that of men and peaks at a younger age by about 10 years. Breast cancer is clearly a stochastic, multifactorial process that evolves over many years in which we must make predictions by likelihood. This review will present the most specially defined and reliably proven of these elements, highlighting anatomic and molecular factors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009521726605
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  • 122
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    The Basic Pathology of Human Breast Cancer (2000)
    Springer
    Journal of mammary gland biology and neoplasia 5 (2000), S. 139-163 
    Details
    ISSN: 1573-7039
    Keywords: breast cancer ; pathology atlas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This article illustrates the most common benign and malignant lesions in the breast, and is intended for the biologist working in the area of breast cancer and breast biology, not for the practicing pathologist. The atlas covers benign proliferative lesions, atypical lesions, variants of in situ cancer, the main types of invasive cancers, spindle cell lesions, and examples of vascular and lymphatic spread. Some entities are included to illustrate a point of particular relevance to the biology and histogenesis of the lesions. Some controversial diagnostic areas are considered, along with the relative risk of developing breast cancer associated with some of the proliferative lesions. The content of this atlas should be read in conjunction with the companion article by Howard and Gusterson in this issue. Their article covers the cellular origin of epithelial and stromal tumors and presents a description of some of the common benign proliferative lesions that are considered to be components of the normal spectrum of changes seen at postmortem or in biopsies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026439204849
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  • 123
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    Mammary Cancer in Humans and Mice: A Tutorial for Comparative Pathology. The CD-ROM (2000)
    Springer
    Journal of mammary gland biology and neoplasia 5 (2000), S. 243-244 
    Details
    ISSN: 1573-7039
    Keywords: mouse mammary gland ; human breast ; oncogenes ; breast cancer ; CD-ROM ; histopathology ; ammary development
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This article introduces a CD-ROM containing whole-mount and histological images of normal growth and development of both the mouse mammary gland and the human breast. It also covers nonneoplastic lesions and neoplasias in both species including a catalog of lesions in genetically engineered mice. Instructions, with examples, on techniques such as whole-mount preparation, immunohistochemistry, in situ hybridization, and common histological stains are provided. The images are based on full-scale 1996 × 1640 pixel images at 300 pixels/inch and are annotated. Every genetically engineered model has one or more accompanying citations. Tables are provided for orientation and organization. The CD includes zoom capabilities, a search engine, and a help mode.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026451607575
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  • 124
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    Biological Features of Premalignant Disease in the Human Breast (2000)
    Springer
    Journal of mammary gland biology and neoplasia 5 (2000), S. 351-364 
    Details
    ISSN: 1573-7039
    Keywords: Human ; breast cancer ; premalignant
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Most human invasive breast cancers (IBCs)4 arise from preexisting benign lesions. There are many types of benign lesions in the human breast and only a few appear to have significant premalignant potential (atypical hyperplasias and in situ carcinomas). These lesions are relatively common and only a small proportion progress to IBC. They are currently defined by their histological features and their prognosis is imprecisely estimated from indirect evidence based on epidemiological studies. Although lesions within specific categories look alike, they must possess morphologically silent biological differences motivating some to remain stable and others to progress. Understanding the biological changes responsible for the development and progression of premalignant disease is a very active area of medical research. Progress in this area may provide new opportunities for breast cancer prevention by providing strategies to treat premalignant lesions before they develop or become cancerous. A large number of biological features have been evaluated in this setting during the past decade. This review discusses a few features that appear to be particularly important and have been studied in a relatively comprehensive manner.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009573710675
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  • 125
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    Influence of chemically modified tetracyclines on proliferation, invasion and migration properties of MDA-MB-468 human breast cancer cells (2000)
    Springer
    Clinical & experimental metastasis 18 (2000), S. 139-146 
    Details
    ISSN: 1573-7276
    Keywords: BRCA1 ; breast cancer ; chemically modified tetracycline ; E-cadherin/catenin ; invasion ; migration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chemically modified tetracyclines (CMTs) are promising anti-cancer agents. In this study, we found that CMT-3 and CMT-8 showed dose-dependent cytotoxicities in MDA-MB-468 human breast cancer cells. Moreover, both CMT-3 and CMT-8 significantly inhibited in vitro cell migration and invasion at non-cytotoxic concentrations. Anti-invasion and migration potentials of the CMTs were associated with an increased expression of E-cadherin/catenins (α, β and γ-catenin) and tumor suppressor BRCA1. In addition, CMT-3 and CMT-8 abolished or reduced spontaneous and HGF/SF-induced cell invasion and migration in U-373 MG human glioblastoma cells. Our current finding is the first demonstration that CMT-3 and CMT-8 can activate the function of invasion suppressor molecules associated with the suppression of breast cancer cell invasion and migration. Thus, clinical application of CMTs may provide potential benefit for suppression of breast cancer growth, invasion and metastasis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006732424102
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    Analysis of mechanisms underlying BRMS1 suppression of metastasis (2000)
    Springer
    Clinical & experimental metastasis 18 (2000), S. 683-693 
    Details
    ISSN: 1573-7276
    Keywords: breast cancer ; chromosome 11q13 ; gap junctions ; metastasis suppressor gene ; motility
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Introduction of normal, neomycin-tagged human chromosome 11 (neo11) reduces the metastatic capacity of MDA-MB-435 human breast carcinoma cells by 70–90% without affecting tumorigenicity. Differential display comparing MDA-MB-435 and neo11/435 led to the discovery of a human breast carcinoma metastasis suppressor gene, BRMS1, which maps to chromosome 11q13.1–q13.2. Stable transfectants of MDA-MB-435 and MDA-MB-231 breast carcinoma cells with BRMS1 cDNA still form progressively growing, locally invasive tumors when injected in mammary fat pads of athymic mice but exhibit significantly lower metastatic potential (50–90% inhibition) to lungs and regional lymph nodes. To begin elucidating the mechanism(s) of action, we measured the ability of BRMS1 to perturb individual steps of the metastatic cascade modeled in vitro. Consistent differences were not observed for adhesion to extracellular matrix components (laminin, fibronectin, type IV collagen, type I collagen, Matrigel); growth rates in vitro or in vivo; expression of matrix metalloproteinases, heparanase, or invasion. Likewise, BRMS1 expression did not up regulate expression of other metastasis suppressors, such as NM23, Kai1, KiSS1 or E-cadherin. Motility of BRMS1 transfectants was modestly inhibited (30–60%) compared to parental and vector-only transfectants. Ability to grow in soft agar was also decreased in MDA-MB-435 cells by 80–89%, but the decrease for MDA-MB-231 was less (13–15% reduction). Also, transfection and re-expression of BRMS1 restored the ability of human breast carcinoma cells to form functional homotypic gap junctions. Collectively, these data suggest that BRMS1 suppresses metastasis of human breast carcinoma by complex, atypical mechanisms.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1013124725690
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    Isolation of genes overexpressed in freshly isolated breast cancer specimens (2000)
    Springer
    Breast cancer research and treatment 59 (2000), S. 41-48 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; bcg-1 ; L19 ; L34 ; MAGE-like ; MLN70 ; subtractive hybridization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A number of approaches have been used to identify genes important in breast cancer. In one approach the genes already shown to be involved in other tumors, such as p53 and Her2neu, were examined. A second approach examined genes detected through genetic screening of families with a high incidence of breast cancer, for example, BRCA-1 and BRCA-2. We used a third approach, subtractive hybridization, to identify and clone genes that were preferentially expressed in breast cancer cells compared to normal mammary epithelium. Instead of analyzing breast cancer cell lines, we examined fresh human breast cancer specimens. By subtracting normal mammary epithelial cDNA from breast cancer cDNA, we were able to clone several genes overexpressed in breast cancer. Two of these genes, L19 and MLN70, were previously reported to be overexpressed in breast cancer. Three of these genes, L19, L34, and MLN70, were localized to a region on chromosome 17 where Her2/neu and BRCA-1 are found. In addition, we isolated a gene we call breast cancer associated gene-1 that was expressed almost exclusively in fresh breast cancer tissue and not in normal mammary epithelium or breast cancer cell lines. We were unable to detect expression of breast cancer associated gene-1 in cell lines from melanoma, renal cell carcinoma, lymphoma, or leukemia. The full-length sequence from two separate breast cancer specimens revealed one amino acid difference compared to the sequence from normal breast epithelial tissue. Further studies are necessary to determine whether these genes contribute to breast cancer development or can be used as therapeutic targets.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006315919985
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    The influence of infiltrating lobular carcinoma on the outcome of patients treated with breast-conserving surgery and radiation therapy (2000)
    Springer
    Breast cancer research and treatment 59 (2000), S. 49-54 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; lobular ; ductal ; conservative surgery ; radiation therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The role of conservative surgery and radiation therapy (CS and RT) in the treatment of patients with infiltrating ductal carcinoma is well established. However, the efficacy of CS and RT for patients with infiltrating lobular carcinoma is less well documented. The goal of this study was to examine treatment outcome after CS and RT for patients with infiltrating lobular carcinoma and to compare the results to those of patients with infiltrating ductal carcinoma and patients with mixed ductal–lobular histology. Methods: Between 1970 and 1986, 1624 patients with Stage I or II invasive breast cancer were treated with CS and RT consisting of a complete gross excision of the tumor and ≥6000 cGy to the primary site. Slides were available for review for 1337 of these patients (82%). Of these, 93 had infiltrating lobular carcinoma, 1089 had infiltrating ductal carcinoma, and 59 had tumors with mixed ductal and lobular feature these patients constitute the study population. The median follow-up time for surviving patients was 133 months. A comprehensive list of clinical and pathologic features was evaluated for all patients. Additional histologic features assessed for patients with infiltrating lobular carcinoma included histologic subtype, multifocal invasion, stromal desmoplasia, and the presence of signet ring cells. Results: Five and 10-year crude results by site of first failure were similar for patients with infiltrating lobular, infiltrating ductal, and mixed histology. In particular, the 10-year crude local recurrence rates were 15%, 13%, and l3% for patients with infiltrating lobular, infiltrating ductal, and mixed histology, respectively. Ten-year distant/regional recurrence rates were 22%, 23%, and 20% for the three groups, respectively. In addition, the 10-year crude contralateral breast cancer rates were 4%, 13% and 6% for patients with infiltrating lobular, infiltrating ductal and mixed histology, respectively. In a multiple regression analysis which included established prognostic factors, histologic type was not significantly associated with either survival or time to recurrence. Conclusions: Patients with infiltrating lobular carcinoma have a similar outcome following CS and RT to patients with infiltrating ductal carcinoma and to patients with tumors that have mixed ductal and lobular features. We conclude that the presence of infiltrating lobular histology should not influence decisions regarding local therapy in patients with Stage I and II breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006384407690
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    The prognostic value of proliferation indices: a study with in vivo bromodeoxyuridine and Ki-67 (2000)
    Springer
    Breast cancer research and treatment 59 (2000), S. 113-123 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; bromodeoxyuridine ; Ki-67 ; nodes ; survival ; S-phase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Proliferation indices are intended to help patients and clinicians make treatment decisions. We have previously demonstrated that a proliferation index based on in vivo labeling of S-phase cells with bromodeoxyuridine (BrdUrd) correlates with Ki-67 labeling index (LI). We now compare the prognostic value of these indices. With written consent, we gave 129 women with biopsy confirmed breast cancer 200 mg/M2 BrdUrd during 30 min immediately preceding surgery. We used IU-4 anti BrdUrd antibody to count the immunohistochemical labeling index (LI) of DNA-incorporated BrdUrd in 2,000 cells and MIB-1 to count Ki-67 (118 cases). Patients received standard surgical and adjuvant treatment. No patients were lost to follow-up and patients were followed a minimum of 2 (median 5.1) years. We compared survival and recurrence in tumors with high vs low labeling indices. We found that women in the low BrdUrd LI group had better disease free survival (92% vs 67% 5-yr DFS p = 0.001) and overall survival (94% vs 70% 5-yr OS, p = 0.0001) than those with a high LI. In comparison, a low Ki-67 index predicted better OS (87% vs 80% 5-yr OS, p = 0.020) and a trend for better DFS (84% vs 72% DFS p = 0.055). The apparent superiority of BrdUrd LI over Ki-67 LI is likely due to chance (p = 0.18). In multivariate survival analyses we found that BrdUrd LI proliferative index significantly improves prediction of DFS or OS even when node status, age or tumor size is in the model. We conclude that markers of proliferation are useful adjuncts in predicting patient prognosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006344010050
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    Survival and tumor characteristics of German hereditary breast cancer patients (2000)
    Springer
    Breast cancer research and treatment 59 (2000), S. 185-192 
    Details
    ISSN: 1573-7217
    Keywords: BRCA1 mutation ; breast cancer ; disease-free survival ; overall survival ; pathology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Reports from different countries have been inconclusive in attempting to relate the BRCA1 mutation status to the survival of breast cancer patients. The purpose of this study was to investigate overall and disease-free survival for German hereditary breast cancer patients. Data on clinical outcome and data on age at diagnosis of breast cancer, histology, tumor size, lymph node status, histological grade, and laterality of 36 breast cancer patients from 12 families with a BRCA1 mutation and from one family with strong evidence for linkage to BRCA1 were compared with those of 49 hereditary breast cancer patients from 23 families that did not harbor a BRCA1 mutation. Overall and disease-free survival was estimated for both groups. BRCA1 mutation carriers had a significantly earlier age of diagnosis than non-carriers (p = 0.0001) and more frequently developed contralateral breast cancer (p = 0.04). Also, BRCA1-associated tumors more frequently were of larger size (p = 0.041) and higher grade of malignancy (p = 0.005) than non-BRCA1-associated tumors. Whereas no difference in overall survival was seen, disease-free survival at 10 years differed significantly with 53.3% for BRCA1 mutation carriers and 76% for non- carriers (p = 0.02). However, after stratification for age and in multivariate analysis for mutation status, age, and bilaterality, it was shown that the worse prognosis for BRCA1 mutation carriers disappeared. Our results suggest that the worse prognosis of BRCA1 mutation carriers in terms of disease-free survival may in large part be due to the age of onset of breast cancer in this population. Thus, BRCA1 mutation status does not appear to be an independent prognostic factor.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006350518190
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  • 131
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    Weekly schedule of vinorelbine in pretreated breast cancer patients (2000)
    Springer
    Breast cancer research and treatment 59 (2000), S. 223-229 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; dose-intensity ; G-CSF ; metastatic ; vinorelbine ; weekly schedule
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: In this phase II study, we explored tolerability and activity of vinorelbine administered according to a dose-dense weekly schedule with hematopoietic growth factor support in pretreated, advanced breast cancer patients. Patients and Methods: From January 1994 to March 1996, 40 patients with metastatic breast cancer, pretreated with at least one prior anthracycline-containing regimen, were entered into the study. Patient characteristics: median age 53 years (range 32–70); ECOG performance status 0-1: 34 patients, 2: 6 patients; dominant visceral metastatic disease: 15 patients, dominant non-visceral: 25; anthracycline-refractory/resistant: 2 patients, sensitive: 38 patients. Six patients were treated as first-line therapy for metastatic disease and 34 in second- or subsequent lines. All patients received vinorelbine at the dose of 25 mg/m2/week as a short intravenous infusion, together with routine antiemetic medication. Granulocyte-colony stimulating factor (Lenograstim) at the dose of 150 μg/m2 subcutaneously on day 3 was included in the treatment schedule. Results: The median number of treatment weeks was 23 (range: 4–24), with a delivered dose-intensity (DDI) of 23.8 mg/m2/week (range: 18.7–25, 95.2% of projected dose-intensity). Toxicity was mild, with non-complicated neutropenia being the main toxicity observed (grade 3–4 in 25% of the patients but only 2% of treatment weeks). Overall response rate was 52.5%, with complete responses in 12.5% of patients. Median duration of the response and median time to progression were 10 and 9 months, respectively. Median overall survival was 19 months. Conclusion: Dose-dense weekly vinorelbine is safe and effective with minimal toxicity in pretreated advanced breast cancer patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006390700480
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  • 132
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    Framing of outcome and probability of recurrence: Breast cancer patients' choice of adjuvant chemotherapy (ACT) in hypothetical patient scenarios (2000)
    Springer
    Breast cancer research and treatment 60 (2000), S. 9-14 
    Details
    ISSN: 1573-7217
    Keywords: adjuvant chemotherapy ; breast cancer ; decision-making ; treatment preference ; decision board instrument
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose.To examine the effects of framing of outcome and probabilities of cancer occurrence on the treatment preference which breast cancer patients indicate for hypothetical patient scenarios. Methods.A modified version of the Decision Board Instrument (Levine et al. 1992) was administered to 35 breast cancer patients with past ACT experience. Patients expressed their choice regarding ACT for six scenarios which were characterized by either negative or positive framing of outcome and by one of the three levels of probability of recurrence (high, medium, low). Results.The framing had no influence on ACT choices over all three probability levels. The majority chose ACT for high and medium risk and one third switched from ACT to No ACT in the low-risk condition. This switch was statistically significant. Conclusion.Hypothetical treatment decisions against ACT occur only when the probability of recurrence is low and the benefit of ACT is small. This finding for patients with past experience of ACT is similar to those reported for other oncological patient groups still in treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006342316373
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  • 133
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    Pre-existent immunity to the HER-2/neu oncogenic protein in patients with HER-2/neu overexpressing breast and ovarian cancer (2000)
    Springer
    Breast cancer research and treatment 62 (2000), S. 245-252 
    Details
    ISSN: 1573-7217
    Keywords: antibody ; breast cancer ; HER-2/neu ; immunity ; ovarian cancer ; T-cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Immunomodulatory strategies, such as antibody therapy and cancer vaccines, are increasingly being considered as potential adjuvant therapies in patients with advanced stage breast cancer to either treat minimal residual disease or prevent relapse. However, little is known concerning the incidence and magnitude of the pre-existent breast cancer specific immune response in this patient population. Using the HER-2/neu oncogenic protein as a model, a well-defined tumor antigen in breast cancer, we questioned whether patients with advanced stage HER-2/neu overexpressing breast and ovarian cancers (III/IV) had evidence of pre-existent immunity to HER-2/neu. Forty-five patients with stage III or IV HER-2/neu overexpressing breast or ovarian cancer were evaluated for HER-2/neu specific T cell and antibody immunity. Patients enrolled had not received immunosuppressive chemotherapy for at least 30 days (median 5 months, range 1–75 months). All patients were documented to be immune competent prior to entry by DTH testing using a skin test anergy battery. Five of 45 patients (11%) were found to have a significant HER-2/neu specific T cell response as defined by a stimulation index ≥ 2.0 (range 2.0–7.9). None of eight patients who were HLA-A2 had a detectable IFNγ secreting T-cell precursor frequency to a well-defined HER-2/neu HLA-A2 T cell epitope, p369-377. Three of 45 patients (7%) had detectable HER-2/neu specific IgG antibodies, range 1.2–8.9 μg/ml. These findings suggest that patients with advanced stage HER-2/neu overexpressing breast and ovarian cancer can mount a T cell and/or antibody immune response to their tumor. However, in the case of the HER-2/neu antigen, the pre-existent tumor specific immune response is found only in a minority of patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006438507898
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  • 134
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    A comparison between flow cytometric assessment of S-phase fraction and Nottingham histologic grade as prognostic instruments in breast cancer (2000)
    Springer
    Breast cancer research and treatment 63 (2000), S. 11-15 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; prognosis ; Nottingham histologic grade ; S-phase fraction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Flow cytometric DNA analysis with assessment of S-phase fraction and DNA ploidy was compared to Nottingham histologic grade. The study population consisted of 654 patients who presented between 1987 and 1996 with primary operable breast cancer and whose tumours had been analysed for S-phase fraction and DNA ploidy at the time of surgery. Grade, tumour size, node status, steroid receptor status, age, S-phase fraction and DNA ploidy were analysed univariately and multi-variately in a Cox proportional hazard analysis. In the univariate analyses all parameters were statistically significantly associated with breast cancer mortality during the follow-up period of 2–11 years. The most powerful predictor of death from breast cancer in the multiple regression analysis was grade. Patients with grade 1 tumours have excellent prognosis. We conclude that tumour grade is a strong prognostic indicator applicable to all breast cancer patients, regardless of size and nodal status, and advocate its general use.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006494625644
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  • 135
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    C-erbB-2 overexpression and survival in early onset breast cancer (2000)
    Springer
    Breast cancer research and treatment 63 (2000), S. 23-29 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; c-erbB-2 ; early onset ; HER-2/neu ; immunohistochemistry ; prognostic factors ; young age
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Young breast cancer patients have a decreased survival rate and it has been demonstrated that young age is an independent predictor of adverse prognosis. Overexpression of c-erbB-2 protein (also known as HER-2/neu) has been shown to be a prognostic indicator in breast cancer in general and especially among patients with axillary nodal metastases. The present study was initiated to determine the prognostic significance of c-erbB-2 protein overexpression in early onset breast cancer. A population consisting of 110 young breast cancer patients, ≤ 36-year-old at diagnosis, was analyzed with immunohistochemical staining for c-erbB-2 protein. Thirty patients (27%) were found to overexpress the c-erbB-2 protein. C-erbB-2 positivity was significantly associated with poor survival when all patients were included in the analysis (P = 0.002) and for patients with axillary nodal metastases (P = 0.0007). No such association was found for node-negative patients. Furthermore, the difference in prognosis in relation to c-erbB-2 among node-positive patients was maintained, when these were stratified in groups treated or not treated with adjuvant chemotherapy. The study indicates that overexpression of c-erbB-2 protein is a strong prognostic factor in young breast cancer patients with axillary nodal metastases. Moreover, the adverse prognosis associated with c-erbB-2 overexpression in node-positive patients was observed whether or not the patients had received adjuvant chemotherapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006498721508
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  • 136
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    A multicenter validation study of sentinel lymph node biopsy by the Japanese Breast Cancer Society (2000)
    Springer
    Breast cancer research and treatment 63 (2000), S. 31-40 
    Details
    ISSN: 1573-7217
    Keywords: axillary lymph node dissection ; breast cancer ; sentinel lymph node biopsy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Several pilot studies have indicated that SLN biopsy can be used to identify axillary lymph node metastases in patients with breast cancer. To confirm this finding, a multicenter study in a variety of practice settings was performed. A total of 674 patients with breast cancer at five institutions were enrolled. The techniques of SLN identification included the vital dye-guided and the vital dye- and gamma probe-guided methods. The SLN was removed, and complete axillary lymph node dissection (ALND) was performed. SLN and ALND specimens were examined separately. The SLN was successfully identified in 214 (94%) of 227 patients using the combined dye- and gamma probe-guided methods. The SLN was identified in 332 (74%) of 447 patients using vital dye-guided method alone. Patient age of at least 51 years, medially located primary tumor, and clinically positive nodes were correlated with failure to identify the SLN. The accuracy of SLN biopsy for the detection of metastatic disease was 96% (522 of 546), and the sensitivity was 90% (203 of 226). Accuracy of 100% was achieved in the patients with tumors less than 1.6 cm in diameter. All 23 false negative results occurred with larger primary tumors. SLN biopsy can accurately predict the presence or absence of axillary lymph node metastases, particularly in patients with small (≤ 1.5 cm) breast cancers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006428105579
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  • 137
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    Induction of matrix metalloproteinases MMP-1 and MMP-2 by co-culture of breast cancer cells and bone marrow fibroblasts (2000)
    Springer
    Breast cancer research and treatment 63 (2000), S. 105-115 
    Details
    ISSN: 1573-7217
    Keywords: bone marrow fibroblasts ; breast cancer ; migration ; matrix metalloproteinases ; MMP-1 ; MMP-2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two invasive breast cancer cell lines (MDA-MB-231 and BT-549) were found to be more adherent and have greater migratory capacity on bone marrow fibroblasts than three non-invasive cell lines (MCF-7, T47D and BT-483). Antibodies to the adhesion molecules CD44, E-cadherin, ICAM-1, and integrin chains α2, α3, α4, α5, α6, αv, α1, α3 and α7 failed to inhibit breast cancer cell migration through bone marrow fibroblasts. Inhibitors of matrix metalloproteases, 1, 10-phenanthroline, Ro-9790, TIMP-1 and TIMP-2 were able to attenuate the migration of MDA-MB-231 cells through bone marrow fibroblast monolayers suggesting a role for these enzymes in the migration of breast cancer cells through bone marrow adherent layers. Co-culture of MDA-MB-231 cells and bone marrow fibroblasts resulted in augmentation of the levels of the matrix metalloproteases MMP-1 and MMP-2 in culture supernatants. Soluble factors produced by bone marrow fibroblasts were responsible for the increase in MMP-1 levels. However, maximal MMP-2 production was dependent on direct contract between the breast cancer cells and the bone marrow fibroblasts. Modulation of MMP production by cell–cell contact or soluble factors suggests a mechanism by which breast cancer cells can enhance their ability to invade the bone marrow microenvironment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006437530169
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  • 138
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    Concurrent adjuvant chemotherapy and immediate breast reconstruction with skin expanders after mastectomy for breast cancer (2000)
    Springer
    Breast cancer research and treatment 60 (2000), S. 267-275 
    Details
    ISSN: 1573-7217
    Keywords: adjuvant chemotherapy ; breast cancer ; mastectomy ; reconstruction ; skin expander-toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. Immediate breast reconstruction (IBR) by means of skin expander is currently one of the most widely used methods of breast reconstruction in mastectomized patients. However, given that many breast cancer patients usually receive adjuvant chemotherapy, the adoption of IBR raises new questions concerning possible cumulative toxicity. The present study reports our experience in the use of concurrent adjuvant chemotherapy and immediate breast reconstruction with skin expander after mastectomy for breast cancer and the acute cumulative toxicity of the treatments. Methods. We evaluated a consecutive series of 52 breast cancer patients who have received IBR by skin expander after radical mastectomy and adjuvant chemotherapy concurrently during skin expansion between 1995 and 1998 (IBR/CT group). We identified two series of control patients treated during the same period: 51 consecutive patients undergoing radical mastectomy and IBR without adjuvant chemotherapy (IBR group) and 63 consecutive patients undergoing radical mastectomy and adjuvant chemotherapy without IBR (CT group). For each patient, we evaluated the incidence of surgical complications and chemotherapy's side effects and dose intensity. Results. The interval between surgery and the start of expander inflation was similar in IBR/CT (range 0–19, median 5 days) and IBR groups (range 0–40, median 5 days) and the timing of inflation was not influenced by chemotherapy. The overall incidence of surgical complications in patients undergoing IBR was low: seroma in eight cases, infection in one, skin necrosis in one, expander rupture in two and erythema in three. There were no statistically significant differences in the distribution of complications between the IBR/CT and IBR groups. The dose intensity of chemotherapy was similar between IBR/CT and CT groups, with a median dose intensity of 96% and 95% of the projected dose, respectively. The only statistically significant difference in terms of chemotherapy side effects (p=0.03) was that stomatitis was more frequent and intense in the CT than in the IBR/CT group. Conclusions. Concurrent treatment with IBR and adjuvant chemotherapy appears feasible and safe, it does not increase acute surgical complications or chemotherapy side effects, and does not require any changes in dose intensity or the timing of inflation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006401403249
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  • 139
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    Cell-mediated immunity to tumor-associated antigens is a better predictor of survival in early stage breast cancer than stage, grade or lymph node status (2000)
    Springer
    Breast cancer research and treatment 60 (2000), S. 227-234 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; cell-mediated immunity ; lymphocyte blastogenesis assay ; prognostic indicators ; tumor-associated antigens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cell-mediated immune (CMI) responses to tumor-associated antigens (TAA) in the early postoperative period were examined for correlations with disease recurrence and survival in a 13-year-prospective study of 77 stage 1 and 2 breast cancer patients treated with modified radical or radical mastectomy alone. Among the 21 patients who had positive lymphoproliferative tests using patients' peripheral blood mononuclear cells and autologous TAA of breast cancer cells, only one died from metastatic disease (5%). Among the 56 patients who had a negative test, 23 died from metastatic disease (41%). This difference is statistically significant (p = 0.002) Three other risk factors including tumor size, nodal status and cell differentiation patterns were also analyzed. When these three clinical-pathologic criteria were analyzed individually, none reliably predicted disease recurrence and survival. Nodal status was the most predictive clinical-pathologic risk factor, but was not significant (p = 0.089). The results of this study demonstrate the detection of CMI responses against autologous TAA by lymphoproliferative assays identifies a sub-set of stage 1 and 2 breast cancer patients who are at minimal risk of developing metastatic disease. This testing also identifies immunologically unreactive patients who are at risk for disease recurrence.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006405504158
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  • 140
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    Electronic Resource
    Pain experienced by women attending breast cancer screening (2000)
    Springer
    Breast cancer research and treatment 60 (2000), S. 235-240 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; cancer screening ; compression ; mammography ; pain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of this study was to evaluate the pain experience of women during mammography for breast cancer screening. Possible associations with personal and medical history, sociodemographics and/or situational factors were studied. It was also investigated whether this pain influenced the intention to return for future breast cancer screening. In the Netherlands, women between 50–75 years are invited for screening every two years. A total of 1200 participants were asked to fill up a questionnaire. The response rate was 79.5% (n = 954), and 945 questionnaires contained adequate information for analyses. A total of 689 women (72.9%) described mammography as mild to severely painful. In this group, compared to the group that reported no pain, the following factors occurred significantly more often: sensitive breasts (P = 0.001), family history of breast diseases (P = 0.017), expected pain based on former mammography (P = 0.001), high education (P = 0.008), anxiety (P = 0.001), breast sensitivity in last three days (P = 0.001), insufficient attention of technologist (P = 0.001). Other factors like age, hormonal status, breast size and hormone use were not associated with the pain experienced. Thirty-two women (3.3%) indicated that they would not attend further screening, 25 (2.6%) reported that the pain might deter them, six women (0.6%) had other reasons, one woman (0.1%) was sure not to come because of severe pain. In conclusion, a large majority of women attending breast cancer screening describes mammography as painful (72.9%). Factors associated with pain were described. Relatively few women (2.7%) indicated that the pain might deter them from future mammography. Recommendations are given to reduce the pain experienced during screening mammography.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006457520996
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  • 141
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    Somatostatin receptor in breast cancer and axillary nodes: study with scintigraphy, histopathology and receptor autoradiography (2000)
    Springer
    Breast cancer research and treatment 61 (2000), S. 21-32 
    Details
    ISSN: 1573-7217
    Keywords: axillary lymphnode metastasis ; breast cancer ; 111In-pentetreotide ; receptor autoradiography ; somatostatin receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We conducted a prospective analysis of somatostatin receptor scintigraphy using 111In radiolabeled pentetreotide, a somatostatin analog, in patients with breast cancer in the aim to visualize the primary tumor and axillary or parasternal metastatic extension because some malignant breast tumors express somatostatin receptors (SS-R) in 50%, approximately. An analysis of SS-R was performed by autoradiography. Patients and methods.Thirteen patients with clinically suspected breast tumors (T1, T2), and at least one palpable axillary node (N1) were included. In vivo planar scintigrams were acquired 1, 4, and 24 h after subcutaneous, then after intravenous injections (24 h delay between injections). Improved 111In-pentetreotide uptake in invaded nodes after subcutaneous injection was hypothesized. Ex vivo scintigrams of surgical specimens were also acquired immediately after tumor resection and axillary dissection. Pathological examination and receptor autoradiography were performed on all surgical specimens. Results.Among 11 pathologically proven malignant tumors (9 ductal and 2 lobular carcinomas), only four were scintigraphically visible although six expressed SS-R receptors in vitro. Among six pathologically proven malignant nodes, four expressed SS-R, including two visualized scintigraphically. Scintigrams acquired after subcutaneous injections were less sensitive than after intravenous injections. There were no false positive. False negatives occurred in cases with small tumors with low-density or heterogeneously distributed SS-R. There was no significant difference by histological type or prognostic factors. Conclusion.Somatostatin receptor scintigraphy does not appear to be sensitive enough to evaluate axillary node extension of breast cancer or even to confirm the presence of tumoral tissue, and this whatever the administration route for 111In-pentetreotide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006447325077
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  • 142
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    p21WAF1/CIP1 Expression in breast cancers: associations with p53 and outcome (2000)
    Springer
    Breast cancer research and treatment 61 (2000), S. 33-43 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; p21WAF1/CIP1 ; p53 ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract p21WAF1/CIP1 is transcriptionally activated by wt p53 and inhibits G1 associated cyclins, a major mechanism by which p53 inhibits cellular proliferation. Archival breast cancers (798) with a median follow-up of 16.3 years were used to explore the prognostic value of p2l immunohistochemical analyses. p21 immunostaining was detected in the majority (726/798: 91%) of breast cancers as well as adjacent in situ carcinomas (125/170: 74%), hyperplastic lesions (140/349: 40%) and normal breast epithelium adjacent to carcinoma (3/89: 3%). Complete immunonegativity was observed in only 9% of invasive cancers and was associated with p53 immunopositivity (p〈0.05). Univariate analysis of all patients showed that p21 negativity was associated with a longer disease specific survival (relative risk (RR) 1.5). Node positive p21 – patients also showed a longer disease free and disease specific survival as compared to tumor p21+ patients. In node negative patients, p53 positivity but not p21 alone, was significantly associated with a shortened disease free survival (RR = 1.6). Node negative patients who were p53 + p21−, in particular had the shortest disease free survival compared to other p53, p21 subgroups (i.e., p21 negativity was associated with a worse outcome). Multivariate analysis of lymph node negative patients (n〉300) demonstrated that tumor size and tumor grade were independently predictive of outcome, whereas neither p53 nor p21 were significant. For node positive patients, p21 positivity (p=0.05), p53 positivity (p=0.03), a higher number of positive nodes, larger tumor size, steroid receptor negativity, high proliferation rate, and erbB-2 expression were each independently associated with poor outcome. In summary, p21 negativity was inversely correlated with p53 immunopositivity in the majority of cases. p21 negative tumor patients had an improved outcome if they were node positive, whereas p21 status was not significantly associated with survival in node negative patients. This observation may be due to the reported ‘uncoupling of S phase and mitosis’ associated with a loss of p21 expression which may result in enhanced sensitivity to chemotherapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006455526894
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  • 143
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    Effect of Melatonin and Linolenic Acid on Mammary Cancer in Transgenic Mice with c-neu Breast Cancer Oncogene (2000)
    Springer
    Breast cancer research and treatment 64 (2000), S. 287-296 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; c-neu transgenic mice ; melatonin ; linolenic acid ; flaxseed oil ; IGF-1 concentrations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Breast cancer is one of the most common cancers and is a leading cause of mortality in women. The TG.NK transgenic mouse line expresses the c-neu breast cancer oncogene under the control of a MMTV promoter and appears to be a useful animal model for evaluation of intervention strategies to delay/prevent breast cancer. Fiber-rich nonpurified diet (NTP-2000) and some retinoid analogues have been shown to significantly delay the development of mammary cancer in the TG.NK model. Four-week-old hemizygous TG.NK female mice with MMTV/c-neu oncogene fed NTP-2000 diet were gavaged with 0.05–0.2 ml of flaxseed oil as the source of ω-3 rich PUFA, or melatonin at 50–200 mg/kg or a combination of 0.10 ml flaxseed oil and 50 mg/kg melatonin in a gavage volume of 0.2 ml per mouse with corn oil as the vehicle for 30 weeks. The time course of the mammary tumor incidence pattern was advanced by flaxseed oil compared to the control. At the high dose (0.2 ml) of flaxseed oil, when the ω-6: ω-3 PUFA ratio was closer to 1, there was some delay in the growth of mammary tumors. Melatonin delayed the appearance of palpable tumors and the growth of the tumors with a dose-related statistically significant negative trend for the incidence of tumors. The combination of flaxseed oil and melatonin caused a significant decrease in the number of tumors and tumor weight per mouse compared to the control and to flaxseed oil but not to melatonin alone. Flaxseed oil may delay the growth of mammary tumors if the ω-6:ω-3 PUFA ratio of fat consumed is closer to 1. Melatonin has the potential to markedly delay the appearance of palpable mammary tumors. Studies are in progress with the TG.NK mouse model to understand the histological and molecular changes associated with the dose-response pattern of mammary tumor incidence and growth after treatment with a broad range of doses of melatonin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026552405042
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  • 144
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    Breast cancer incidence in relation to smoking cessation (2000)
    Springer
    Breast cancer research and treatment 61 (2000), S. 121-129 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; ex-smokers ; smoking ; smoking cessation ; tobacco
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract High plasma levels of oestrogens are associated with increased breast cancer risk. If smoking, as has been suggested, have both a tumour initiating mutagenic effect and a protective anti-oestrogenic effect, one would assume that smokers who give up smoking have the highest incidence of breast cancer. This was evaluated in the follow-up of a cohort of 10,902 women of whom 4,359 were premenopausal. Record-linkage with official cancer registries yielded 416 incident cases during an average follow-up of 13.6 years. The adjusted relative risk in all ex-smokers was 1.31 (1.02–1.69), as compared to never smokers, and in premenopausal ex-smokers it was 1.57 (1.07–2.30). Breast cancer incidence in premenopausal ex-smokers was inversely related to time since cessation, (p for trend = 0.01), and was highest among the women who had given-up smoking less than 12 months before screening: 2.76 (1.55–4.91). There was no significant association between current smoking and breast cancer risk. We conclude that incidence of breast cancer in premenopausal women who have given up smoking is higher than it is in smokers and never smokers. To what extent this may be related to endocrine effects associated with smoking cessation remains to be evaluated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006448611952
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  • 145
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    Improving discussion of surgical treatment options for patients with breast cancer: local medical opinion leaders versus audit and performance feedback (2000)
    Springer
    Breast cancer research and treatment 61 (2000), S. 171-175 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; breast conserving surgery ; hospital practices ; mastectomy ; physician behavior
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We studied whether a hospital intervention utilizing medical opinion leaders and performance feedback reduced the proportion of women who reported that surgeons did not discuss options prior to surgery for early stage breast cancer. Opinion leaders provided clinical education to their peers using a variety of strategies and were selected for their ability to influence their peers. Performance feedback involved distributing performance reports that contained data on the outcomes of interest as well as on other treatment patterns. Twenty-eight hospitals in Minnesota were randomized to the intervention or to a control group that received performance feedback only. The proportion of patients at intervention hospitals who said that their surgeon did not discuss options decreased significantly (p〈0.001) from 33% to 17%, but a similar decrease was observed among control hospitals. Using medical opinion leaders to intervene in hospitals appeared as effective as performance feedback.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006475012861
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  • 146
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    Electronic Resource
    Breast cancer prognostic significance of a single nucleotide polymorphism in the proximal androgen response element of the prostate specific antigen gene promoter (2000)
    Springer
    Breast cancer research and treatment 61 (2000), S. 111-119 
    Details
    ISSN: 1573-7217
    Keywords: androgen receptor ; breast cancer ; mutation ; polymorphism ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Prostate Specific Antigen (PSA) expression by breast epithelial cells is associated with favorable breast cancer prognosis. In preliminary studies, we found that a nucleotide variation (G → A) at position −158 in the androgen response element (ARE-1) of the PSA promoter was present in four out of 9 breast tumors examined and in a breast carcinoma cell line. We have now determined the nucleotide composition at position −158 of DNA extracted from 148 well-characterized breast tumors and compared tumor genotype with that of controls without cancer, with tumor PSA concentration and with clinicopathological variables, overall survival and disease free survival. The G → A base change at position −158 is a polymorphism. Allelotypes were similarly distributed in breast cancer patients and controls. The Mann–Whitney U Test showed a significantly higher tumor PSA concentration in tumors that presented a homozygous G as opposed to homozygous A genotype. Genotype at position −158 was not associated with clinicopathological variables in contingency table analysis. Univariate Cox regression models showed a 28% reduction in risk for death in patients with homozygous G genotype compared to those with homozygous A genotype (P=0.03). However, ARE-I genotype did not significantly add to the prognostic power in the multivariate model of overall survival. In summary, the base change at position −158 is a polymorphism that may affect breast cancer prognosis, but further studies are required to confirm this possibility and to investigate the relevance of this polymorphism in terms of breast cancer susceptibility.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006459613498
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  • 147
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    Electronic Resource
    Pilot studies on the p53 gene in nipple aspirate fluid from patients with breast cancer (2000)
    Springer
    Breast cancer research and treatment 61 (2000), S. 139-143 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; mutation ; nipple aspirate fluid ; p53
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Nipple Aspirate Fluid (NAF) from patients with breast cancer is a potential source of exfoliated tumour material amenable to molecular biological study, but few such data have been reported. In this study we demonstrate that polymerase chain reaction (PCR) amplification of p53 gene DNA is achievable in a proportion of NAF samples from breast cancer patients. Subsequently four NAF samples from patients whose primary tumours were identified as having a defined p53 mutation were studied by single stranded conformational polymorphism analysis (SSCP). Two samples yielded PCR product indistinguishable from wild type and two yielded no product. Whilst no cancer-related genetic mutations were demonstrated in NAF samples, further study is warranted.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006487315587
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  • 148
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    Psychological distress following first recurrence of disease in patients with breast cancer: prevalence and risk factors (2000)
    Springer
    Breast cancer research and treatment 61 (2000), S. 145-150 
    Details
    ISSN: 1573-7217
    Keywords: adjustment disorders ; breast cancer ; first recurrence ; major depressive disorder ; psychological distress
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objectives: To investigate the prevalence of, and risk factors for psychological distress following first recurrences of breast cancer. Patients and methods: The sample was drawn consecutively from the inpatient and outpatient populations of the National Cancer Center Hospital in Japan during an 18-month period from July 1996 to December 1997. Of the 56 eligible patients, 55 women aged 30–73 year with recurrent breast cancer participated in the study. The prevalence of psychological distress, including major depressive disorder and adjustment disorders was evaluated according to the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Third edition-revised (DSM-III-R). Risk factors for psychological distress were analyzed with a logistic regression model. Results: Of the 55 subjects, 42 met the DSM-III-R criteria for major depressive disorder or adjustment disorders. Major depressive disorder was seen in 4 (7%), and adjustment disorders in 19 (35%). Logistic regression analysis showed that a disease-free interval of less than 24 months significantly predicted a diagnosis of major depressive disorder or adjustment disorders (odds ratio 5.28, 95% confidence interval; 1.28–21.8, p=0.02). Conclusions: These results suggest that it is important for all oncology staff to pay careful attention to the psychological health of patients who have been informed of their cancer recurrence, and that some psychosocial intervention is necessary for preventing distress in patients facing early recurrence.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006483214678
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  • 149
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    Electronic Resource
    A comparison of cell cycle markers in well-differentiated lobular and ductal carcinomas (2000)
    Springer
    Breast cancer research and treatment 61 (2000), S. 161-170 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; cell cycle ; ductal ; histologic subtypes ; lobular
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Infiltrating lobular carcinoma (ILC) and infiltrating ductal carcinoma (IDC) are similar in many respects and their histologic features occasionally overlap. Despite the many similarities, some clinical follow-up data and the patterns of metastasis suggest that ILC and IDC are biologically distinct. Unfortunately, most breast cancer research has focused almost exclusively on the ductal subtype or has not stressed the biologic or molecular genetic distinctions between breast carcinoma subtypes. Several reports have suggested the possibility that ILCs and IDCs differ with respect to expression of antigens involved in proliferation and cell cycle regulation. Therefore, we undertook an immunohistochemical evaluation of cell cycle related antigens in ILCs, including histologic variants thought to represent aggressive neoplasms, and IDCs matched for histologic grade (Modified Bloom–Richardson Grade I). We believe that different antigent expression profiles could elucidate the biological distinctiveness of breast carcinoma subtypes and possibly provide diagnostically relevant information. We studied the expression of the following antigents in 28 archived, formalin-fixed ILCs and 34 well-differentiated IDCs: estrogen receptor (ER), progesterone receptor (PR), Her 2-neu, mib-1, cyclin D1, p27, p53, mdm-2 and bcl-2. 94% of ILCs and 100% of IDCs expressed ER; 75% of ILCs and 76% of IDCs expressed PR; 4% of ILCs and 13% of IDCs expressed c cerb B-2; ILCs and IDCs both expressed mib-1 in approximately 10% of lesional cells; 82% of ILCs and 54% of IDCs expressed cyclin D1; 90% of ILCs and 83% IDCs expressed p27 strongly; 4% of ILCs and 4% of IDCs expressed p53, 25% of ILCs and 33% of IDCs expressed mdm-2; 96% of ILCs and 100% of IDCs expressed bcl-2. None of the apparent differences were statistically significant. The ILC variants demonstrated immunophenotypes that were essentially similar to ILCs of the usual type. We conclude that ILCs and well-differentiated IDCs show similar proliferation and cell cycle control antigen profiles. Despite their unusual histologic features, most ILC variants appear to maintain a characteristic ILC immunophenotype.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006479113769
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  • 150
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    The growth and metastasis of human, HER-2/neu-overexpressing tumor cell lines in male SCID mice (2000)
    Springer
    Breast cancer research and treatment 61 (2000), S. 217-228 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; in vivo tumor models ; Her-2/neu ; metastasis ; SCID mice ; soluble Her-2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract HER-2/neu is overexpressed on a variety of human adenocarcinomas and overexpression has been associated with a poor prognosis. For this reason, HER-2 has become an attractive target for immunotherapy. To facilitate testing of anti-HER-2-monoclonal antibodies (MAbs) and immunotoxins (ITs), we have evaluated the in vivo growth and metastatic spread of three HER-2-overexpressing human breast cancer cell lines (BT474, MDA-MB-453 and HCC1954) and one ovarian cancer cell line (SKOV3.ip1) in pre-irradiated male SCID mice using subcutaneous (s.c.), intravenous (i.v.) and intraperitoneal (i.p.) routes of injection. All the cell lines tested grew as s.c. tumors and the growth of BT474 and MDA-MB-453 cells after s.c. injection was improved by co-inoculation with Matrigel. Metastases to the lungs were detectable by PCR or histopathology after s.c. injection of BT474 and to a much lesser extent after s.c. injection of HCC1954, MD-MB-453 and SKOV3.ip1cells. I.P. injection of HCC1954 and SKOV3.ip1 cells produced fatal ascites while i.v. injection of SKOV3.ip1, but not BT474 or MDA-MB-453 cells, resulted in infiltration of lungs and death within 9–11 weeks.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006494001861
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  • 151
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    Increased risk of second cancers following breast cancer: Role of the initial treatment (2000)
    Springer
    Breast cancer research and treatment 61 (2000), S. 183-195 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; chemotherapy ; cohort study ; radiotherapy ; second primary cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objectives and methods.The risk of second primary malignancies (SMN) was studied in a cohort of 4,416 one-year survivors of a breast cancer. The role of the menopausal status and of the initial treatment modalities (surgery, radiotherapy, and chemotherapy) was investigated. Results.Excluding second primary breast cancer and non-melanoma skin cancer, a total of 193 (4.4%) patients developed a SMN between 1973 and 1992, compared with 136 expected (Standardised Incidence Ratio, SIR = 1.4, 95% CI (1.2–1.6)). No trend towards either an increase or a decrease was noted in the SIR with time after treatment (p = 0.2). The greatest increase in the relative risk concerned soft tissue cancers (SIR = 13.0, 95% CI: 6.8–22.3), followed by leukaemia (SIR = 3.1, 95% CI: 1.7–5.0), melanoma (SIR  =  2.7, 95% CI: 1.4–4.8), kidney (SIR = 2.5, 95% CI: 1.2–4.5), ovary (SIR = 2.0, 95% CI: 1.2–3.1) and uterine tumours (SIR = 1.9, 95% CI: 1.4–2.5). The SIR was 3.0 (95% CI 1.8–4.7) in women under 40 at the time of the breast cancer, 1.9 (95% CI : 1.4 – 2.4) in those aged 40–49 and 1.2 (95% CI 1.0–1.4) in those aged 50 or more. In the 2,514 women who had received radiotherapy as initial treatment without chemotherapy, the SIR for all SMN was 1.6 (95% CI: 1.1–2.3) fold higher than in those who had not received radiotherapy as initial treatment. Conclusion.In conclusion, this study confirms the increased risk of second malignancies in women treated for a breast cancer, and particularly in those who were younger at the time of treatment for breast cancer. Our results also suggest that radiotherapy may play a role in the onset of these second lesions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006489918700
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  • 152
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    Pathways through which a regimen of melatonin and retinoic acid induces apoptosis in MCF-7 human breast cancer cells (2000)
    Springer
    Breast cancer research and treatment 61 (2000), S. 229-239 
    Details
    ISSN: 1573-7217
    Keywords: apoptosis ; breast cancer ; melatonin ; retinoic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It has been established that melatonin (Mlt) and retinoic acid, individually, inhibit the proliferation of the estrogen receptor-alpha (ERα)-positive MCF-7 breast cancer cell line. Our laboratory has previously demonstrated that Mlt and all-trans-retinoic acid (atRA) not only inhibit the proliferation, but also induce apoptosis of MCF-7 cells when used in a sequential regimen of Mlt followed 24 h later by atRA. Using this same MCF-7 breast cancer cell line, we investigated the potential pathways through which apoptosis is being induced. We found that treatment of MCF-7 cells with Mlt for 24 h before the addition of atRA decreased the protein levels of the death suppressor, Bcl-2, and increased, although with different time courses, the levels of the death promoters, Bax and Bak; however, there was no change in the levels of the tumor suppressor gene, p53. MCF-7 cells treated sequentially with Mlt and atRA also demonstrated an enhanced sensitivity to the apoptotic effects of atRA, which did not appear to be due to increased expression of the retinoic acid receptors, RARα or RXRα, but rather to enhanced transcriptional activity of the RARα. These data suggest that the sequential treatment regimen of Mlt and atRA may induce apoptosis by modulation of members of the Bcl-2 family of proteins. Thus, this combinatorial regimen, which reduces the concentration of atRA needed for clinical efficacy while enhancing its anti-tumorigenic activity, could be of great therapeutic benefit, and may, in fact, specifically induce the regression of established breast tumors due to its apoptosis-promoting effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006442017658
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  • 153
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    Electronic Resource
    Predication of axillary lymph node metastasis by intravenous digital subtraction angiography in breast cancer, its correlation with microvascular density (2000)
    Springer
    Breast cancer research and treatment 61 (2000), S. 261-269 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; intravenous digital subtraction angiography ; axillary lymph node metastasis ; neovascularization of lymph nodes ; microvascular density ; antibody to platelet/endothelial cell adhesion molecule
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Accurate predication of axillary node status by non-invasive diagnostic method would be of great value in cases of breast cancer. There have been few reports advocating digital subtraction angiography (DSA) as specifically advantageous for the detection of lymph node metastasis. IV (intravenous)-DSA was carried out on 42 patients with breast carcinoma using a DSA system with a matrix of 1024 × 1024×pixels. When a mass became stained in the axilla, it was considered to be metastatic. An immunohistochemical technique with JC70 antibody to platelet/endothelial cell adhesion molecules was used to evaluate the microvascular density (MVD) of the axillary lymph nodes. IV-DSA achieved a 76.2% sensitivity, 85.7% specificity, and 81.0% accuracy. The average MVD with JC70 antibody was 97.7 ± 44.4 in metastatic and 62.9 ± 23.6 in nonmetastatic nodes. MVD was significantly higher in the cancerous than in the noncancerous regions within lymph nodes. The MVD was 105 ± 38.4 in DSA-N(+) cases and was 57.8 ± 21.9 in DSA-N(−) cases, and the difference was statistically significant. In conclusion, IV-DSA is a useful diagnostic modality for detection of axillary lymph node metastasis. This new modality predicts lymph node status by assessing the neovascularization of the lymph node.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006449619475
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  • 154
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    Electronic Resource
    Contortrostatin, a dimeric disintegrin from contortrix contortrix, inhibits breast cancer progression (2000)
    Springer
    Breast cancer research and treatment 61 (2000), S. 249-259 
    Details
    ISSN: 1573-7217
    Keywords: adhesion ; breast cancer ; disintegrin ; integrins ; invasion ; metastasis ; angiogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report the results of a multidisciplinary study on the inhibitory effect of a snake venom disintegrin, contortrostatin, a 13.5 kDa homodimeric protein isolated from Agkistrodon contortrix contortrix (southern copperhead) venom, on breast cancer progression. We demonstrate that contortrostatin binds to integrins and blocks the adhesion of human breast cancer cells (MDA-MB-435) to extracellular matrix (ECM) proteins including fibronectin and vitronectin, but it has no effect on adhesion of the cells to laminin and Matrigel. Contortrostatin also prevents invasion of MDA-MB-435 cells through an artificial Matrigel basement membrane. Daily local injection of contortrostatin (5 μg per mouse per day) into MDA-MB-435 tumor masses in an orthotopic xenograft nude mouse model inhibits growth of the tumor by 74% (p = 0.0164). More importantly, it reduces the number of pulmonary macro-metastasis of the breast cancer by 68% (p 〈 0.001), and micro-metastasis by 62.4% (p 〈 0.001). Contortrostatin is not cytotoxic to cancer cells, and does not inhibit proliferation of the breast cancer cells in vitro. However, contortrostatin inhibits angiogenesis induced by the breast cancer, as shown by immunohistochemical quantitation of the vascular endothelial cells in tumor tissue removed from the nude mice. We have identified αvβ3, an important integrin mediating cell motility and tumor invasion, as one of the binding sites of contortrostatin on MDA-MB-435 cells. We conclude that contortrostatin blocks αvβ3, and perhaps other integrins, and thus inhibits in vivo progression.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006457903545
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  • 155
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    Electronic Resource
    Expression of Bcl-2 but not Bax or p53 correlates with in vitro resistance to a series of anticancer drugs in breast carcinoma (2000)
    Springer
    Breast cancer research and treatment 61 (2000), S. 211-216 
    Details
    ISSN: 1573-7217
    Keywords: Bcl-2 ; breast cancer ; chemosensitivity ; HDRA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Programmed cell death is an important determinant of the response to chemotherapy. Among the factors controlling this process, a significant role is played by bcl-2, bax and p53. The in vitro chemosensitivity of the 177 breast carcinomas was assessed by the histoculture drug response assay (HDRA) using mitomycin C (MMC), 5-fluorouracil (5-Fu), adriamycin (ADM), cisplatin (CDDP), and cyclophosphamide (CPA). The susceptibility of Bcl-2-negative tumors to all the drugs killing was significantly higher than that of Bcl-2-positive tumors. No relationship between Bax or p53 immunoreactivity and sensitivity for any of anticancer drugs studied was demonstrated. Immunohistochemical results regarding Bcl-2 are promising in the evaluation of the sensitivity of cancer cells to a series of anticancer drugs and might be therapeutically useful as an indicator of response to adjuvant chemotherapy for breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006474307180
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  • 156
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    Electronic Resource
    Chemoprevention of breast cancer (2000)
    Springer
    Breast cancer research and treatment 62 (2000), S. 1-17 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; prevention ; tamoxifen ; raloxifene ; SERMs ; retinoids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Despite a recent trend toward improvement in the U.S. breast cancer mortality rate, breast cancer incidence (182,800 new cases anticipated in 2000) and mortality figures (over 40,800 anticipated deaths) remain the highest and second highest, respectively, of all cancers in U.S. women. In 1998, the selective-estrogen-receptor-modulator (SERM) tamoxifen achieved positive results in the Breast Cancer Prevention Trial (BCPT), leading to the Food and Drug Administration (FDA) approval of tamoxifen for risk reduction in women at high risk of breast cancer (the historic first FDA approval of a cancer preventive agent). This brought about a paradigm shift in new approaches for controlling breast cancer toward pharmacologic preventive regimens, called chemoprevention. This paper presents a comprehensive clinical review of breast cancer prevention study, highlighting issues of the extensive study of tamoxifen. These issues include the record of primary tamoxifen results in several breast-cancer risk-reduction settings (primary, adjuvant, and ductal carcinoma in situ [DCIS]); critical secondary BCPT risk-benefit findings (including quality of life issues) and their effects on counseling patients on use of tamoxifen for prevention; ethic minorities; optimal tamoxifen dose/duration; and potential impact on mortality and other issues involved with potential net benefit to society. Other breast-cancer chemoprevention issues reviewed here include women at high genetic risk (especially BRCA1 mutation carriers); raloxifene in breast cancer prevention; other SERMs; SERM resistance; and new agents and combinations currently in development. Very recent developments involving PPAR-γ ligands, COX-2 inhibitors, and RXR-ligands are discussed in the section on new drug development.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006484604454
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  • 157
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    Electronic Resource
    Management of familial breast cancer risk (2000)
    Springer
    Breast cancer research and treatment 62 (2000), S. 19-33 
    Details
    ISSN: 1573-7217
    Keywords: BRCA1 ; BRCA2 ; breast cancer ; familial risk ; risk management
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Women who are members of breast cancer families are at increased risk for breast cancer. The cloning of BRCA1 and BRCA2 has made it possible to identify mutation carriers within some of these families. Management of breast cancer risk in these families, which presents enormous challenges to patients and clinicians, is addressed. Management should begin with a full evaluation of the patient, including construction of a three-generation pedigree, ascertainment of non-genetic factors that may impact on risk, information on previous and current breast health, practice of and attitudes toward screening, and the psychosocial impact of family history on the individual. Patient priorities in risk management should be explicitly reviewed; these may include survival, cancer prevention, breast preservation, optimization of quality of life or minimization of disruption of day-to-day activities. Approaches to risk management involve screening (usually considered the mainstay), anti-estrogens, prophylactic surgery and/or lifestyle modifications. Specific gene therapy may become available in the future. Management decisions should be individualized to reflect risk levels and patient priorities and goals, within bounds that are medically and scientifically reasonable. An explicit examination of different time-frames (1, 5, 10 years) is recommended given the rapid evolution of knowledge in this area.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006470206271
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  • 158
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    What drove changes in the use of breast conserving surgery since the early 1980s? The role of the clinical trial, celebrity action and an NIH consensus statement (2000)
    Springer
    Breast cancer research and treatment 62 (2000), S. 71-79 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; breast conserving surgery ; clinical trial ; celebrity ; consensus statement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background.Three important events in the history of breast cancer treatment occurred between 1983 and 1995: a large clinical trial, first lady Nancy Reagan's choice of mastectomy and the publishing of an NIH consensus statement. Objective.To assess the effects of these events on use of breast conserving surgery (BCS). Research design.Data from the cohort study of the surveillance, epidemiology and end results (SEER) Program from 1983 to 1995 were divided into four periods: Baseline, Trial, Celebrity, and Consensus. Subjects.Of the women, 169,466 diagnosed with early stage breast cancer in nine SEER areas. Measures.Monthly percentages of BCS. Results.A linear regression model generated a separate intercept and slope term for four time periods, adjusting for demographic characteristics of breast cancer patients. For the Baseline, Celebrity and Consensus Periods, slopes indicated an increasing use of BCS which varied between 0.24% and 0.28% per month. Slopes for these three periods were not statistically different (p = 0.120). In contrast, there was no change in use of BCS during the trial period (p = 0.247). We tested the magnitude of discontinuity between periods. At the beginning of the trial, celebrity and consensus periods, there were increases in BCS of 5.54% (p 〈 0.001), −3.55% (p 〈 0.001), and 2.37% (p 〈 0.001), respectively. Conclusions.The use of BCS was substantially affected by the reports of a clinical trial of BCS and by celebrity action. These effects were abrupt but transient. The NIH consensus statement stimulated a small change in use of BCS and may be an important intervention for maintaining the increasing trend in use of BCS since the 1990s.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006414122201
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  • 159
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    Ras activation in human breast cancer (2000)
    Springer
    Breast cancer research and treatment 62 (2000), S. 51-62 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; epidermal growth factor receptor ; ErbB-2 receptor ; mitogen-activated protein kinase ; ras
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Genetic ras mutations are infrequent in breast cancer but Ras may be pathologically activated in breast cancer by overexpression of growth factor receptors which signal through Ras. Using a highly sensitive, coupled enzymatic assay, we measured Ras activation in 20 breast cancers, two fibroadenomas, and seven normal breast samples. Ras was highly activated compared to benign tissue in 11 of the 20 cancer; 7 of these 11 cancers expressed both the epidermal growth factor (EGF) and ErbB-2/neu/HER-2 receptors with the remaining four cancers with high Ras activation expressing one of these two receptors. In the other nine cancers, Ras activation was similar to that observed in benign breast tissue with none of these cancers expressing the EGF receptor while one expressed the ErbB-2 receptor. None of the cancers tested had an activating K-ras mutation nor did any of the cancers express a truncated EGF receptor or the c-FMS receptor. The activity of mitogen-activated protein (MAP) kinase was high in the cancers, and reflected the degree of Ras activation. In cultured mammary tumor cell lines, we showed that Ras activation was ligand dependent in cells overexpressing the ErbB-2 receptor. Thus, Ras was abnormally activated in breast cancers overexpressing the EGF and/or ErbB-2 receptors indicating there are sufficient ligands in vivo to activate these receptors, and this work provides a basis for new target-based treatments of this disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006491619920
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  • 160
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    The risk of nodal metastases in breast cancer patients with clinically negative lymph nodes: a population-based analysis (2000)
    Springer
    Breast cancer research and treatment 62 (2000), S. 63-69 
    Details
    ISSN: 1573-7217
    Keywords: axillary dissection ; breast cancer ; nodal metastases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A population-based study was performed to assess the likelihood of axillary lymph node metastases in patients with clinically negative lymph nodes, according to patient age, tumor size and site, estrogen receptor status, histologic type and mode of detection. Data were obtained from the population-based Eindhoven Cancer Registry. During the period 1984–1997, 7680 patients with invasive breast cancer were documented, 6663 of whom underwent axillary dissection. Of the 5125 patients who were known to have clinically negative lymph nodes and underwent axillary dissection, 1748 (34%) had positive lymph nodes at pathological examination. After multivariate analysis, histologic type, tumor size, tumor site and the number of lymph nodes in the axillary specimen remained as independent predictors of the risk of nodal involvement (P 〈 0.001). Lower risks were found for patients with medullary or tubular carcinoma, smaller tumors, a tumor in the medial part of the breast and patients with less than 16 nodes examined. This study gives reliable estimates of the risk of finding positive lymph nodes in patients with a clinically negative axilla. Such information is useful when considering the need for axillary dissection and to predict the risk of a false-negative result when performing sentinel lymph nodebiopsy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006447825160
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  • 161
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    Cisplatin–epirubicin–paclitaxel weekly administration with G-CSF support in advanced breast cancer. A Southern Italy Cooperative Oncology group (SICOG) phase II study (2000)
    Springer
    Breast cancer research and treatment 62 (2000), S. 87-97 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; paclitaxel ; epirubicin ; cisplatin ; weekly administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose.It has been shown in vitro that both cisplatin and epirubicin increase the antitumor activity of paclitaxel. Weekly administration could give a substantial improvement in the therapeutic index of cisplatin and paclitaxel. This study was aimed at defining the antitumor activity of a weekly cisplatin–epirubicin–paclitaxel (PET) administration in locally advanced or metastatic breast cancer patients. Patients and methods.Sixty-eight breast cancer patients with advanced disease, who had not received prior chemotherapy (except adjuvant), received weekly cisplatin 30 mg/sqm, paclitaxel 120 mg/sqm and epirubicin 50 mg/sqm plus G-CSF (day 3–5), for a maximum of 12 cycles. Thirty-five patients had stage IIIB and 33 stage IV disease (14 with visceral metastases). Results.All patients were evaluable for response on an intent to treat basis. Overall, 21 complete and 38 partial responses have been recorded for an 87% ORR (95% CI = 76–94%). Fourteen CRs and 19 PRs have been registered in the 35 patients with locally advanced disease for a 94% ORR (95% CI = 81–99%) while 7 CRs and 19 PRs were observed in the 33 patients with metastatic disease for a 79% ORR (95% CI–61–91%). Surgery was performed in 33/35 women with locally advanced disease. Four of these patients (11%) showed no invasive cancer on pathologic examination, and in an additional 8 patients tumor 〈 1 cm was found in the breast. Only 4/33 patients who underwent surgery relapsed. The projected one-year RFS was greater than 80%. At an 11-month median follow-up (range, 3–19), 11 patients had progressed and 5 had died among the 33 patients with metastatic disease, the median progression-free survival in this group being 14 months. Severe hematologic toxicity was uncommon, grade 3–4 neutropenia and thrombocytopenia occurring in 32% and 4% of patients, respectively. Only 2 episodes of neutropenic sepsis were registered. Packed red blood cell transfusions were required in 7 patients. Vomiting, diarrhoea, mucositis and skin toxicity were severe in 6%, 9%, 10%, and 9% of patients, respectively. Peripheral neuropathy was observed in 47% of patients. Conclusions.The weekly PET administration is a well tolerated and very effective approach in advanced breast cancer patients. It can produce a 40% clinical complete response rate, with a more than 10% pCR rate in patients with T4 disease, and an about 80% ORR in those with distant metastases. A phase III trial comparing PET with a standard every 3 weeks epirubicin—taxol administration is underway.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006429205363
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  • 162
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    Electronic Resource
    Quality of life after adjuvant chemotherapy for breast cancer (2000)
    Springer
    Breast cancer research and treatment 62 (2000), S. 141-150 
    Details
    ISSN: 1573-7217
    Keywords: adjuvant chemotherapy ; breast cancer ; quality of life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose.To evaluate the quality of life of breast cancer patients previously treated with adjuvant chemotherapy. Method.Registry data were used to recruit a sample of breast cancer patients (N = 61; mean age = 51.6 years) with no current evidence of disease who had completed adjuvant chemotherapy between 3 and 36 months earlier (average = 15.87 months). In addition, a peer nomination procedure was used to recruit an age-matched comparison group of women with no history of cancer (N = 59; mean age = 51.5 years). Both groups were mailed a survey to complete that included the Medical Outcomes Study Short Form 36 (SF-36) and the Center for Epidemiologic Studies Depression Scale (CES-D). These data were used to test the hypothesis that breast cancer patients previously treated with adjuvant chemotherapy experience impaired quality of life relative to their peers and to identify demographic and medical factors associated with individual differences in patient quality of life. Results.Consistent with predictions, the postchemotherapy group scored poorer than the noncancer comparison group on the CES-D and on six of the eight subscales as well as the physical component summary scale of the SF-36 (p 〈 0.05). With regard to individual differences in patient quality of life, younger age and unmarried status were positively related to poorer mental well-being and greater depressive symptomatology (p 〈 0.05). Time since cancer diagnosis and chemotherapy completion were also positively related to greater depressive symptomatology (p 〈 0.05). In contrast, none of the demographic or medical variables assessed were related to physical well-being (p 〉 0.05). Conclusions.Breast cancer patients appear to experience problems in multiple quality of life domains following the completion of adjuvant chemotherapy treatment. Demographic and medical characteristics explain individual differences in mental but not physical aspects of patient quality of life. These findings demonstrate the need for interventions to improve the quality of life in breast cancer patients previously treated with adjuvant chemotherapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006401914682
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  • 163
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    Electronic Resource
    High complete pathological response in locally advanced breast cancer using paclitaxel and cisplatin (2000)
    Springer
    Breast cancer research and treatment 62 (2000), S. 237-244 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; locally advanced ; neoadjuvant ; chemotherapy ; paclitaxel ; cisplatin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background.In an earlier study, we have demonstrated a high response rate in metastatic breast cancer using paclitaxel (P) and cisplatin (C). A phase II study using the same regimen (PC) has been conducted in locally advanced breast cancer (LABC). Methods.A total of 72 consecutive patients with non-inflammatory LABC (T2 ≥ 4 cm, T3 or T4, N0–N2, M0). Patients were scheduled to receive 3–4 cycles of the neoadjuvant PC (paclitaxel 135 mg/m2 and cisplatin 75 mg/m2 on day 1) every 21 days. Patients were then subjected to surgery and subsequently received 6 cycles of FAC (5-fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2) or 4 cycles of AC (doxorubicin 60 mg/m2, and cyclophosphamide 600 mg/m2). Patients then received radiation therapy, and those with hormone receptor positive tumors were given adjuvant tamoxifen intended for 5 years. Results.The median age was 39 years (range, 24–78). Clinically, 7%, 58%, and 35% of patients had T2 ≥ 4 cm, T3, and T4, respectively. Disease stage at diagnosis was IIB (33%), IIIA (27%), and IIIB (40%). Complete and partial clinical response to PC was demonstrated in 13 (18%), and 52 (72%) patients, respectively. Of those patients with evaluable pathologic response (68 patients), complete pathologic response (pCR) was achieved in 15 (22%) patients. At a median follow-up of 22 (± 3.5) months, 58 (81%) were alive with no recurrence, nine (12%) were alive with evidence of disease, and five (7%) were dead. None of the patients achieving pCR has developed any relapse. The median overall survival has not been reached for all 72 patients with a projected 3-year survival (± SE) of 90% (± 4%). The median progression-free survival (PFS) was 42.1 (± 4.8) months with a projected PFS of 74% ± 7% at 3-years (for 68 patients). Conclusions.PC regimen in LABC produced a high pCR. The contribution of the other added modalities to survival could not be assessed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006434406989
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  • 164
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    Electronic Resource
    99m-Tc-tetrofosmin scintigraphy for the evaluation of suspicious palpable and non-palpable breast lesions (2000)
    Springer
    Breast cancer research and treatment 62 (2000), S. 253-258 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; 99m-Tc-tetrofosmin ; whole-body scintigraphy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose.To assess the value of 99m-Tc-tetrofosmin (tetrofosmin) scintigraphy in patients with palpable and non-palpable breast lesions. Patients and methods.Prospective, blinded trial. One hundred and fifty-nine consecutive patients with 163 breast lesions detected by clinical examination and mammography were included. Tetrofosmin scintigraphy of the breast was performed additionally to the regular diagnostic procedure. Using histologic assessment as the golden standard, sensitivity, specificity, positive and negative predictive value for tetrofosmin scintigraphy of the breast were assessed. Results.Overall sensitivity and specificity were 82% and 84%. The sensitivity for palpable tumors (65%) was 93% compared to 62% for non-palpable breast lesions. Malignant lesions were nearly twice as big as benign lesions (31.5 mm± 2.4 vs. 16.9 mm ± 2.4). Specificity, positive and negative predictive value (84%, 89%, and 66%) did not differ significantly in palpable versus non-palpable tumors. Of malignant tumors 18% were found false negative by tetrofosmin scintigraphy. Conclusion.The results suggest that tetrofosmin scintigraphy is a valuable tool for the evaluation of palpable breast cancer. In patients with non-palpable tumors, tetrofosmin scintigraphy may not add to the work-up of patients with breast cancer due to a low sensitivity rate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006442622417
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  • 165
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    Electronic Resource
    Formestane is feasible and effective in elderly breast cancer patients with comorbidity and disability (2000)
    Springer
    Breast cancer research and treatment 62 (2000), S. 217-222 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; comorbidity ; disability ; elderly ; formestane ; hormonal treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Age is a major risk factor for solid tumors, including breast cancer. The majority of elderly breast cancer patients have oestrogen-dependent tumors, thus, tamoxifen is widely administered. However, it has been noted that tamoxifen-related thrombotic events are not exceptional. Due to the increasing prevalence of comorbidity, including vascular diseases, with age, such events are more frequently observed in the aged patients. Formestane, a selective steroidal aromatase inhibitor, may represent a therapeutic option after failure with tamoxifen, or in the presence of vascular diseases contraindicating its administration. The present report provides a new clinical experience on a consecutive series of 45 elderly breast cancer women affected by moderate to severe degree of comorbidity and disability measured by a Comprehensive Geriatric Assessment (CGA) scale validated on oncological patients. Formestane was given intramuscularly at the dose of 250 mg every 2 weeks. The study included 31 patients who had metastatic disease, and 14 who received formestane as an adjuvant treatment. Median age was 74 years (range 65–93), with nine patients 〉 80 years. Median ECOG Performance Status (PS) was one. The more frequent comorbidities observed in our series were arthrosis-arthritis (64.4% of patients), hypertension (44.4%), vascular diseases (35.5%), CNS diseases (28.8%). Twenty percent of patients presented at least one dependency in Activities of Daily Living (ADL) and 51.2% in Instrumental Activities of Daily Living (IADL). The treatment was well tolerated – only two patients interrupted formestane because of minor adverse reaction at the injection site and generalised itching. In particular Formestane was not responsible for any worsening of pre-treatment comorbidities, especially hypertension and vascular diseases. Objective responses (OR) were observed in 11.1% of advanced patients, while the disease was stabilised in 51.8% subjects. Median duration of OR was 12 months; median overall survival was 11 months. Among patients receiving formestane as adjuvant treatment, three relapsed, with a time to failure (TTF) of 12 months. Formestane is effective and minimally toxic in an elderly breast cancer population with comorbidities and disabilities measured by CGA.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006490524736
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  • 166
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    Electronic Resource
    Clinicopathological characteristics of breast carcinomas with allelic loss in the p73 (2000)
    Springer
    Breast cancer research and treatment 63 (2000), S. 17-22 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; p73 gene ; LOH ; high-grade malignancy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract p73, a new member of the p53 family, has been mapped to chromosome 1p 36, a region where loss of heterozygosity (LOH) is frequently observed in primary human tumors. Allelic loss studies involving the 1p arm in breast carcinomas offer rates ranging from 13% to 75%, depending on the genetic interval being studied. We investigated LOH in an intragenic microsatellite marker, and those centromerically flanking the p73 gene, at 1p 36, and their correlations with patient age and 10 pathologic parameters in a series of 193 breast carcinomas. The LOH analysis was performed by amplifying DNA by PCR, using five markers of the 1p 36 region (p73P1, D1S2694, D1S214, D1S2666 and D1S450). LOH was found in at least one of these markers in 27% of tumors. When we established the comparison between tumors with and without LOH and the distribution of the 10 pathologic parameters considered, we observed statistically significant differences in association with higher histologic grade (p = 0.02), more advanced pathological stage (p = 0.02), peritumoral vessel involvement (p = 0.04) and poorly differentiated carcinomas (p = 0.01), as well as in tumors that concomitantly exhibited lymph node metastases, peritumoral vessel involvement and absence of steroid receptors (p = 0.02). These data suggest that LOH in the p73 region could be pathogenically related to breast cancer and possibly to a poor tumor prognosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006446709715
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  • 167
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    Electronic Resource
    Human alpha – Fetoprotein peptides bind estrogen receptor and estradiol, and suppress breast cancer (2000)
    Springer
    Breast cancer research and treatment 63 (2000), S. 41-52 
    Details
    ISSN: 1573-7217
    Keywords: alpha fetoprotein ; breast cancer ; estradiol ; estrogen receptor ; peptides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Alpha-fetoprotein (AFP) is a transporter of various serum ligands and regulator of cellular growth during pregnancy. Estrogens modify AFP to exhibit growth suppressive properties. We recently synthesized a peptide (P149) from human AFP that suppresses the growth of mouse uterus and MCF-7 breast cancer cells. Here it is shown that molar excess treatment of native AFP with estradiol-17β (E2) exposes the P149 site on AFP. The anti-estrogenic and anti-tumor activities of AFP-peptides were tested in vivo in the immature mouse uterine assay and mammary tumor (6WI-101)-induced ascites assay, and in vitro in a cytostatic assay using five different human breast tumor cell lines. AFP-peptide P149, and fragments of P149, P149A and P149C but not P149B, suppressed the growth in both in vivo assays. P149 also suppressed the in vitro growth of MCF-7, MDA-MB-231, MDA-MB435 breast cancer cells by more than 75%. P149 and P149A bound the estrogen receptor-α (ER) with low affinities compared to E2 and tamoxifen, while P149B bound 3H-E2 with 105 fold less affinity compared to ER. The recent epidemiologic observation that high AFP levels in young pregnant women reduce their subsequent risk of postmenopausal breast cancer may be related to the growth suppressive property of AFP with the exposed P149 epitope.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006484223325
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  • 168
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    Flow cytometric analysis of primary tumors and their corresponding metastatic nodes in breast cancer (2000)
    Springer
    Breast cancer research and treatment 63 (2000), S. 81-87 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; heterogeneity ; lymph nodes ; ploidy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Human breast carcinoma is biologically heterogeneous, and its clinical course may vary from one which is indolent to one which rapidly progresses. Although it is the metastasis rather than the primary tumor that ultimately overwhelms the patients, studies concerning the DNA pattern have focused on the primary tumors. This study was undertaken to identify heterogeneities between primary tumors and metastases, and to evaluate the prognostic significance of the ploidy pattern and the S-phase fraction (SPF) of metastatic nodes in axillary node positive patients. Seventy-four frozen specimens of the primary and corresponding metastatic nodes from 37 patients have been analyzed by flow cytometry and the SPF calculated. The results of ploidy pattern analysis in primaries revealed 25 diploidy (67.6%) and 12 aneuploidy (32.4%), while those in metastasis showed 17 diploidy (46.0%) and 20 aneuploidy (54.0%). The aneuploidy group in metastatic nodes had the poorer histological grade (85.0% vs. 15.0%, p = 0.02), and more mean metastatic nodes (5.75 ± 2.10 vs. 3.05 ± 1.56, p = 0.018), and more frequent lymphatic vessel invasion (65.0% vs. 11.8%, p = 0.031) than its counterpart. Decreased expression of ER (70.6% vs. 25.0% p = 0.006) and increased expression of c-erbB2 (65.0% vs. 23.5%, p = 0.012) were observed in the aneuploidy of metastatic nodes. The group with higher SPF in metastatic nodes had more metastatic nodes (5.47 ± 2.31 vs. 4.00 ± 1.78, p = 0.042), and the higher incidence of lymphatic vessel invasion (57.9% vs. 22.2%, p = 0.027), and poor histological grade (71.4% vs. 37.5%, p = 0.039). In conclusion, the cell populations in metastatic nodes revealed DNA pattern which differed from that of primary tumors. The ploidy pattern and SPF in metastatic nodes might be considered as discriminate measure for risk factors in breast cancer patients with positive axillary node.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006470614782
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  • 169
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    Inhibitory effects of Indole-3-carbinol on invasion and migration in human breast cancer cells (2000)
    Springer
    Breast cancer research and treatment 63 (2000), S. 147-152 
    Details
    ISSN: 1573-7217
    Keywords: Indole-3-carbinol ; breast cancer ; invasion ; migration ; PTEN ; E-cadherin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Indole-3-carbinol (I3C) is a promising phytochemical agent in chemoprevention of breast cancer. Our present study is the first description of I3C that significantly inhibits the cell adhesion, spreading and invasion associated with an up-regulation of PTEN (a tumor suppressor gene) and E-cadherin (a regulator of cell–cell adhesion) expression in T47-D human breast cancer cells. Therefore, I3C exhibits anti-cancer activities by suppressing breast tumor cell growth and metastatic spread. Metastatic breast cancer is a devastating problem, clinical application of I3C as a potent chemopreventive agent may be helpful in limiting breast cancer invasion and metastasis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006495824158
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  • 170
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    Electronic Resource
    Local feedback mechanisms in human breast cancer (2000)
    Springer
    Breast cancer research and treatment 63 (2000), S. 95-104 
    Details
    ISSN: 1573-7217
    Keywords: feedback mechanisms ; paracrine regulation ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Breast function and development are controlled by a variety of both local and systemic signals. Many of these signals are exerted by hormones and cytokines which are believed to be effectors in autoregulatory feedback loops. Recent studies have also suggested the involvement of such mechanisms in human breast cancer. For example, the disruption of a negative feedback system by malignant transformation can result in the loss of growth control or in increased malignant behavior of tumor cells. Conversely, pathological positive feedback loops can develop that enhance tumor growth and invasion by excessive release of stimulatory factors. These loops are often located at the site of tumor invasion and involve stromal–epithelial interactions. They can be composed of mutually stimulating or inhibiting cytokines and may include locally expressed sex steroids. Although most studies have concentrated on cell–cell interactions at the site of the primary tumor, a number of observations indicate their importance in metastases as well. A thorough analysis of the regulatory mechansims within a malignant tumor is essential for the understanding of its unique behavior and for the investigation of more specific breast cancer therapies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006430202101
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  • 171
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    Electronic Resource
    Effects of Bcl-2 modulation with G3139 antisense oligonucleotide on human breast cancer cells are independent of inherent Bcl-2 protein expression (2000)
    Springer
    Breast cancer research and treatment 63 (2000), S. 199-212 
    Details
    ISSN: 1573-7217
    Keywords: antisense oligodeoxynucleotides ; antineoplastic agents ; apoptosis ; Bcl-2 ; breast cancer ; chemosensitization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have investigated the effects of transient Bcl-2 down-regulation induced by the Bcl-2 antisense oligodeoxynucleotide (ODN) G3139 (Genta Incorporated) in high Bcl-2 protein expressing, estrogen receptor (ER) positive MCF-7 and low Bcl-2 expressing, ER negative MDA435/LCC6 human breast cancer cells. Treatment with Bcl-2 antisense ODN in vitro caused 〉 80% reduction of Bcl-2 protein levels in a sequence specific manner for both cell lines. Maximum mRNA reduction was achieved within 24 h of the first antisense ODN exposure whereas full protein down-regulation required antisense exposure over 48 h. This Bcl-2 reduction was associated with 80–95% loss of viable cells compared to untreated cells. Similar cytotoxic effects were observed in both cell lines despite a nine-fold intrinsic difference in Bcl-2 protein expression suggesting that the relative degree of down-regulation of Bcl-2 is more important than the absolute reduction. Cell death associated with G3139 exposure exhibited properties indicative of apoptosis such as mitochondrial membrane depolarization and caspase activation. Combined treatment with G3139 and cytotoxic agents resulted in additive cytotoxicity in both cell lines. However, under most conditions studied, the direct cytotoxic activity of G3139 antisense was not synergistic with the cytotoxic agents. These results suggest that while Bcl-2 clearly constitutes an attractive therapeutic target due to its role in regulating apoptosis in breast cancer cells, additional mechanisms are important in the control of apoptosis arising from exposure to anticancer agents in vitro.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1017371013487
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  • 172
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    Biphasic effect of medroxyprogesterone-acetate (MPA) treatment on proliferation and cyclin D1 gene transcription in T47D breast cancer cells (2000)
    Springer
    Breast cancer research and treatment 63 (2000), S. 243-248 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; cyclin D1 ; MPA ; proliferation ; T47D cell line
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract While progesterone is a known differentiation-inducing factor in the human endometrium, for the breast epithelium both proliferation-inducing and -inhibiting effects have been described. Cyclin D1, which is required for cell cycle progression in G1 and has been shown to play an important role in the pathogenesis of breast cancer has been implicated as a possible mediator of such effects. In the present study we thus investigated the effects of the progestin agonist MPA (medroxy-progesterone acetate) on proliferation of T47D breast cancer cells. In parallel experiments, the regulation of the human cyclin D1 promoter as well as cyclin D1 protein levels under the influence of MPA were studied. Our results show an increase of proliferative activity in T47D cells after 24 and 48 h of MPA treatment follwed by inhibition of proliferation after 72 h. In Western blot analysis an increased expression level of cyclin D1 protein can be observed after 24 h of MPA stimulation, while at 72 h the protein levels are barely detectable. Transient transfection experiments with a luciferase reporter plasmid containing the human cyclin D1 promoter showed an induction of the promoter after 24 and 36 h of MPA treatment followed by a reduction in promoter activity. In conclusion, our results confirm the existence of a biphasic response of T47D cell proliferation in response to MPA treatment, consisting of stimulation of proliferation followed by inhibition, and further implicate cyclin D1 as a mediator of these effects, since the cyclin D1 promoter shows a similar biphasic response in this context.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006432600478
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  • 173
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    Polyadenylic–Polyuridylic Acid Plus Locoregional Radiotherapy Versus Chemotherapy with CMF in Operable Breast Cancer: a 14 Year Follow-up Analysis of a Randomized Trial of the Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) (2000)
    Springer
    Breast cancer research and treatment 64 (2000), S. 189-191 
    Details
    ISSN: 1573-7217
    Keywords: adjuvant treatment ; breast cancer ; chemotherapy ; immunotherapy ; radiotherapy ; randomized trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract With a median follow-up of 14 years, the combination of polyadenylic–polyuridylic acid plus locoregional radiotherapy (257 patients) has significantly improved disease-free survival (p = 0.03) and significantly reduced the incidence of metastases (p = 0.04) when compared to CMF alone (260 patients), in women with operable breast cancer. The trial does not, however, permit an appreciation of the respective role of radiotherapy and PolyAU in these results.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006498121628
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  • 174
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    Selective Decrease of Serum Immunoglobulin G1 as Marker for Early Stages of Invasive Breast Cancer (2000)
    Springer
    Breast cancer research and treatment 64 (2000), S. 193-199 
    Details
    ISSN: 1573-7217
    Keywords: affinity chromatography ; breast cancer ; immunoglobulin G subclasses ; sensitivity ; specificity ; tumor marker, %IgG1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The diagnostic value of the decrease in percentage of immunoglobulin G1 (%IgG1) in breast cancer was analyzed with special emphasis on early tumor stages. IgG1 and total IgG were preoperatively measured in the sera of a total of 801 individuals using a modified quantitative affinity chromatography. Group A consisted of 174 healthy individuals of both sexes, group B of 324 female patients with benign breast disease, and group C of 303 patients with invasive and non-invasive breast cancer. Within group C, 13 patients presented with intraductal carcinoma, and 22 patients with a pT1a-tumour (diameter less than 0.5 cm). The %IgG1 values were compared among groups A, B and C. In addition, correlations were sought between %IgG1 values of group C and tumor size, stage (UICC), histopathological grade and oestrogen (ER) and progesteron receptor (PR) expression. The mean value of %IgG1 in group A was 63.3 ± 0.5 s.e.m., in group B 57.75 ± 0.4 s.e.m. and in group C 52.37 ± 0.5 s.e.m. The differences of mean values were highly significant between all three groups. Sensitivity and specificity of %IgG1 to discriminate between group A and C were 75% and 87%, and between group B and C 62% and 63%, respectively. The significant decrease of %IgG1 in total serum IgG is able to distinguish patients with breast cancer of more than 5 mm in diameter from healthy controls and patients with benign breast diseases. Finally, calculated posterior probabilities revealed that within certain concentration limits %IgG1 may provide predictive information with high xprobabilities.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006450205698
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  • 175
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    Inhibition of NF-κB Activity Enhances TRAIL Mediated Apoptosis in Breast Cancer Cell Lines (2000)
    Springer
    Breast cancer research and treatment 64 (2000), S. 211-219 
    Details
    ISSN: 1573-7217
    Keywords: apoptosis ; breast cancer ; caspases ; NF-κB ; TRAIL
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Most breast cancer cell lines are resistant to TNF-related apoptosis inducing ligand (TRAIL) induced apoptosis. In sensitive breast cancer cell lines TRAIL rapidly induces the cleavage and activation of caspases leading to the subsequent cleavage of downstream caspase substrates. In contrast, there is no caspase activation in the resistant cell lines. The transcription factor NF-κB can inhibit apoptosis induced by a variety of stimuli including activation of death receptors. We investigated whether NF-κB contributes to the resistance of breast cancer cells to TRAIL induced apoptosis. All of the resistant breast cancer cell lines expressed NF-κB and had detectable NF-κB activity in nuclear extracts prior to treatment with TRAIL. Upon TRAIL treatment, a significant increase in NF-κB activity was seen in most of the cell lines. To directly test if NF-κB activity contributes to the resistance of these cell lines to TRAIL, we transiently transfected the resistant cell lines with an inhibitor of NF-κB (IκBΔN) and measured TRAIL induced apoptosis in control and transfected cells. All of the resistant cell lines tested showed an increase in TRAIL induced apoptosis when transfected with the IκBΔN. These results demonstrate that TRAIL resistant breast cancer cells fail to rapidly activate the apoptotic machinery but they do activate NF-κB. Inhibition of NF-κB activity increases the sensitivity to TRAIL mediated apoptosis in resistant cells. These results suggest that agents which inhibit NF-κB should increase the clinical efficacy of TRAIL in breast cancer cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006458407515
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  • 176
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    Utilization of Professional Supportive Care Services by Women with Breast Cancer (2000)
    Springer
    Breast cancer research and treatment 64 (2000), S. 253-258 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; psychosocial ; supportive care ; utilization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This paper reports on the results of a survey of utilization of professional supportive care services by women with breast cancer, and on patterns of differential service utilization by sub-groups of patients. Study participants were women with invasive breast cancer diagnosed 23–36 months prior to contact about the study, and randomly selected from the Ontario Cancer Registry. From among 1,119 eligible women sent survey questionnaires, 731 returned completed questionnaires (65%). A total of 31% of respondents reported accessing one or more of the following professionals: social worker, psychologist, psychiatrist, dietitian, physiotherapist. Among those who responded to a question about whether they would have liked specific services, 34% reported that there was at least one professional supportive care service they would have liked to use, but were unable to access. Factors shown to be related to greater utilization of services included: younger age, higher household income, employed or student status, private health insurance coverage, and having received chemotherapy. Overall, there was a surprisingly low utilization of professional specialized supportive care services among women with breast cancer. Policy implications include finding strategies to better inform cancer patients about existing services, and ensuring that a core set of services are available to all patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026548320063
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  • 177
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    Long-Term Morbidity Following Axillary Dissection in Breast Cancer Patients – Clinical Assessment, Significance for Life Quality and the Impact of Demographic, Oncologic and Therapeutic Factors (2000)
    Springer
    Breast cancer research and treatment 64 (2000), S. 275-286 
    Details
    ISSN: 1573-7217
    Keywords: axillary dissection ; breast cancer ; morbidity ; quality of life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective. This study describes in detail the surgery-related symptoms following axillary lymph node dissection in breast cancer patients and considers both their significance for long term quality of life and the impact of possible influencing factors. Material and methods: Three hundred and ninety six patients were studied retrospectively using a self-report questionnaire and a clinical examination. The symptoms, numbness, pain, edema, arm strength and mobility were evaluated. The subjective assessment of the degree of symptom intensity was compared with objective measurements. The extent of surgery (number of resected nodes, level of dissection) as well as the influence of demographic, oncologic and adjuvant measures (age, time interval, number of involved nodes, chemotherapy) were evaluated. Results. Shoulder-arm morbidity and fear of cancer recurrence were the most important long-term sources of distress following breast cancer surgery in our study population. Demographic, oncologic and therapeutic measures including the extent of surgery had no influence on long-term morbidity. The intensity of all evaluated symptoms was reported to be more severe in patients' subjective statements than in the results of clinical assessment. Conclusion. Shoulder-arm morbidity following axillary dissection is a frustrating polysymptomatic disease that seems to be relatively unaffected by therapeutic measures. The surgical trauma necessary for adequate tumor staging (removal of 10 lymph nodes) seems decisive for the postsurgery syndrome following axillary dissection. For node-positive patients complete axillary clearing may improve tumor control without worsening long-term-morbidity. New techniques, such as the sentinel-node-biopsy, that selects patients with negative axillary status while preserving the integrity of axillary structures, may improve the overall morbidity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026564723698
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  • 178
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    Cancer Risk Associated with Subfertility and Ovulation Induction: A Review (2000)
    Springer
    Cancer causes & control 11 (2000), S. 319-344 
    Details
    ISSN: 1573-7225
    Keywords: breast cancer ; endometrial cancer ; fertility drugs ; infertility ; melanoma ; ovarian cancer ; thyroid cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: Over the past decades the use of fertility drugs (FDs) has greatly increased. Recently, the possible association between the use of FDs and risk of cancer has aroused great concern. In this paper, we critically review the available epidemiologic studies. Methods: We identified papers published between 1966 and 1999 that examined FDs and specific causes of subfertility in relation to the risks of cancers of the ovary, breast, endometrium and thyroid, and melanoma. Results: Although present insights into the pathogenesis of hormone-related malignancies suggest a possible association between the use of FDs and the risk of specific cancers, this has not been convincingly demonstrated in epidemiologic studies. With regard to cancer risk in relation to the cause of subfertility, the only consistent association observed is an increased risk of endometrial cancer for women with subfertility due to hormonal disorders. While positive findings in some studies on FDs and ovarian cancer risk have aroused serious concern, the associations observed in most of these reports appear to be due to bias or chance rather than being causal. The most important sources of bias are inadequate confounder control for both parity and causes of subfertility. Conclusions: To discriminate between the possible carcinogenic effects of various ovulation induction regimens, subfertility disorders, and reproductive characteristics associated with subfertility, future studies should include large populations of subfertile women with sufficient follow-up time. In such cohort studies the cause of subfertility should be measured adequately (based on medical records) and information about reproductive characteristics should be collected for all cohort members. Such studies should also include a group of subfertile women with an indication for FD use but not so treated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008921211309
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  • 179
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    Weight change and risk of postmenopausal breast cancer (United States) (2000)
    Springer
    Cancer causes & control 11 (2000), S. 533-542 
    Details
    ISSN: 1573-7225
    Keywords: breast cancer ; body weight ; case–control study ; postmenopausal ; weight gain ; weight loss
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: Although many studies have shown that higher weight increases the risk of postmenopausal breast cancer, some aspects of this association are unclear. In order to examine the risk associated with different patterns of weight change, we analyzed data from a large case–control study of postmenopausal breast cancer. Methods: Participants included women aged 50–79 years (n = 5031) who are newly diagnosed with invasive breast cancer in Massachusetts, New Hampshire, and Wisconsin. Similarly-aged population controls (n = 5255) were selected at random from driver's license files and Medicare beneficiary lists. Height, weight, and information on other breast cancer risk factors were ascertained by structured telephone interviews from 1992 to 1995, and logistic regression was used to estimate multivariable-adjusted odds ratios (OR) and 95% confidence intervals (CI). Results: Women in the top quintile groups for height at age 20, recent weight, and recent body mass index had significantly increased risks of breast cancer. Among women who reached their highest adult weight at younger ages (≤45 years), increasing weight loss since that age was associated with a reduced risk of postmenopausal breast cancer (OR 0.90, CI 0.84–0.98, per 5 kg). However, weight loss among women whose highest weight occurred after age 45 was not associated with risk (OR 1.00, CI 0.95–1.05, per 5 kg). Weight gain since the lowest adult weight increased risk by 8% for each 5 kg of gain (OR 1.08, CI 1.06–1.11). Temporary weight cycling (weight loss followed by weight gain) was not associated with increased risk. Conclusions: Weight gain clearly increased risk of postmenopausal breast cancer. These data lend further support to efforts aimed at helping women avoid weight gain as they age.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008961931534
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  • 180
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    Association of mammographically defined percent breast density with epidemiologic risk factors for breast cancer (United States) (2000)
    Springer
    Cancer causes & control 11 (2000), S. 653-662 
    Details
    ISSN: 1573-7225
    Keywords: breast cancer ; breast density ; mammographic density ; risk factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: Mammographically defined percent breast density is an important risk factor for breast cancer, but the epidemiology of this trait is poorly understood. Although several studies have investigated the associations between reproductive factors and density, few data are available on the associations of breast density and waist-to-hip ratio (WHR), physical activity, education, alcohol and smoking. Methods: We investigated the associations of known and suspected breast cancer risk factors with breast density in a large breast cancer family study. Information was collected on members of 426 families through telephone interviews, mailed questionnaires and mammography. Mammographic films on 1900 women were digitized and breast density was estimated in discrete five-unit increments by one radiologist. Analysis of covariance techniques were used and all analyses were performed stratified by menopausal status. Results: Similar to other reports, nulliparity, late age at first birth, younger age and lower body mass index were associated with increased percent density in both premenopausal and postmenopausal women, and hormone replacement therapy among postmenopausal women. Higher levels of alcohol consumption and low WHR were associated with increased percent density among both premenopausal and postmenopausal women (differences of 3–11% between high and low categories). However, smoking and education were inversely associated with percent density among premenopausal (p = 0.004 and p = 0.003, respectively) but not postmenopausal women (p = 0.52 and p = 0.90). Physical activity was not associated with percent density in either stratum (p values 〉 0.25). Combined, these factors explained approximately 37% of the variability in the percent density measure in premenopausal women and 19% in postmenopausal women. Conclusions: Many of these factors may potentially affect breast cancer risk through their effect on percent breast density.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008926607428
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  • 181
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    Breast cancer following augmentation mammoplasty (United States) (2000)
    Springer
    Cancer causes & control 11 (2000), S. 819-827 
    Details
    ISSN: 1573-7225
    Keywords: breast cancer ; breast implants ; incidence ; mortality ; prognosis ; silicone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective:Although clinical reports have raised concern that breast implants may either increase the risk of breast cancer or delay its diagnosis, epidemiologic studies have generally shown implant recipients to be at a reduced risk of subsequent breast cancer. A large retrospective cohort study was undertaken to clarify effects of cosmetic breast implantation. Methods:Medical records of 13,488 women receiving cosmetic implants at 18 plastic surgery practices and a group of 3936 patients who received other types of plastic surgery at the same practices were reviewed and information abstracted. Questionnaires were sent to all subjects located as alive, with 71% being completed. Attempts were made to obtain medical verification for all reported cancers and to obtain death certificates for deceased subjects. Results:A total of 136 breast cancers were observed among the breast implant patients. External analyses, using general population rates from the Surveillance, Epidemiology and End Results (SEER) program, resulted in 152.2 cases expected and a standardized incidence ratio (SIR) of 0.9 (95% CI 0.8–1.1). A comparable SIR was found for the other plastic surgery patients (SIR = 1.0, 95% CI 0.7–1.2). Internal analyses, directly comparing the implant patients with the other plastic surgery patients, showed a RR of 0.8 (95% CI 0.6–1.1). In neither the external nor internal analyses was there any systematic variation in risk by age or calendar year of initial implant. Risk also did not vary by years of follow-up or by type of implant. Risk was not affected by exclusion of patients who received their implants following surgery for benign breast disease. Although breast tumors tended to be detected at a somewhat later stage among the breast implant than the comparison patients, the difference was not statistically significant, nor was there any significant difference in breast cancer mortality between the two groups. Conclusions:Breast implants do not appear to alter the risk of subsequent breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008941110816
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  • 182
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    The diagnostic and prognostic utility of prostate-specific antigen for diseases of the breast (2000)
    Springer
    Breast cancer research and treatment 59 (2000), S. 1-14 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; prostate-specific antigen ; prognostic indicators ; tumor markers ; breast cyst ; benign breast disease ; molecular forms of prostate-specific antigen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Although prostate-specific antigen (PSA) is the most valuable tumor marker for the diagnosis and management of prostate carcinoma, it is widely accepted that PSA is not prostate specific. Numerous studies have shown that PSA is present in some female hormonally regulated tissues, principally the breast and its secretions. In this review, we summarize the findings of PSA in the breast, and focus on its potential for clinical applications in breast disease. PSA is produced by the majority of breast tumors and is a favorable indicator of prognosis in breast cancer. Low levels of PSA are released into the female circulation, and while the level of serum PSA is elevated in both benign and malignant breast disease, the molecular form of circulating PSA differs between women with and without breast cancer. These findings indicate that PSA may have potential diagnostic utility in breast cancer. PSA may also have a clinical application in benign breast disease, as both the level and molecular form of PSA differ between Type I and II breast cysts. High levels of PSA have been reported in nipple aspirate fluid (NAF) and recent studies have shown that the concentration of PSA in NAF is inversely related to breast cancer risk, indicating that NAF PSA may represent a clinical tool for breast cancer risk assessment. Thus, PSA represents a marker with numerous potential clinical applications as a diagnostic and/or prognostic tool in breast disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006380306781
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  • 183
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    Results of two or five years of adjuvant tamoxifen correlated to steroid receptor and S-phase levels (2000)
    Springer
    Breast cancer research and treatment 59 (2000), S. 69-76 
    Details
    ISSN: 1573-7217
    Keywords: estrogen and progesterone receptor ; S-phase fraction ; tamoxifen ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A Swedish cooperative trial demonstrated that 5 years of adjuvant tamoxifen was more beneficial than 2 years of tamoxifen in the treatment of postmenopausal women with estrogen receptor (ER) positive, early stage, invasive breast cancer. The main aim of the present study was to investigate the importance of progesterone receptor (PgR) and ER concentration levels for patients participating in the trial and still distant recurrence free two years after the primary operation. Subgroup analyses revealed that only patients with ER positive and PgR positive breast cancer had improved distant recurrence free survival (DRFS) by prolonged tamoxifen therapy (p=0.0016). Patients with ER negative and PgR negative as well as ER positive and PgR negative tumors showed no significant effect of prolonged tamoxifen (p=0.53 and p=0.80, respectively). The percentage of ER negative and PgR positive breast cancers was too small (2.2%) for any meaningful subgroup analysis. There was a significant positive trend that the concentration level of PgR (high positive vs. low positive vs. negative) decreased the recurrence rate for those with prolonged therapy. No corresponding pattern was found for the ER content. S-phase fraction did not correlate to the recurrence rate of PgR positive breast cancers. Patients recurring during tamoxifen therapy had receptor negative tumors to a greater extent than those recurring after tamoxifen treatment. In conclusion, prolonged tamoxifen therapy for 5 years instead of 2 years was found to be beneficial for patients with ER positive and PgR positive breast cancer, whereas three extra years of tamoxifen had little or no effect for patients with ER positive but PgR negative tumors as well as for steroid receptor negative patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006332423620
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  • 184
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    Surgical treatment of hepatic metastases from breast cancer (2000)
    Springer
    Breast cancer research and treatment 59 (2000), S. 177-184 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; metastasis ; liver metastasis ; surgical procedure ; hepatectomy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have performed a retrospective study to evaluate whether surgical treatment is beneficial in patients with hepatic metastases from breast cancer. Between September 1985 and September 1998, 25 patients with hepatic metastases (14 solitary and 11 multiple), eight of whom had extrahepatic metastases, underwent hepatectomy. All of the detectable liver metastasis were resected in all of the cases. There were no severe postoperative complications. All but one of the patients received adjunctive polychemotherapy after the hepatectomy. After the hepatectomy, recurrent tumors were detected in 18 of the patients, being located in the liver in 12 (67%) of them. Overall, however, hepatectomy ensured that the liver was clinically recurrence-free for a median of 24 months (range 2–132 months). Eleven patients died of recurrent tumors, two died of other causes and the remaining 12 are currently alive. The 2- and 5-year cumulative survival rates after hepatectomy were 71% and 27%, respectively, and the median survival duration was 34.3±3.2 months, much better than the period of 8.5 months for another series of patients treated with standard or non-surgical therapies at our institution. The number and the size of hepatic metastases, the interval between treatment of the primary lesion and hepatectomy, and the existence of extrahepatic metastasis were not adverse prognostic factors. In conclusion, our data, although limited and highly selective, suggest that surgical treatment of hepatic metastases from breast cancer may prolong survival in certain subgroups of patients to a greater extent than standard or non-surgical therapies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006398401352
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  • 185
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    Quantitative measurement of soluble cytokeratin fragments in tissue cytosol of 599 node negative breast cancer patients: a prognostic marker possibly associated with apoptosis (2000)
    Springer
    Breast cancer research and treatment 59 (2000), S. 211-221 
    Details
    ISSN: 1573-7217
    Keywords: apoptosis ; breast cancer ; continuous variables statistical analysis ; cytokeratins ; multiple correspondence analysis ; prognosis ; tissue cytosol ; tissue polypeptide antigen (TPA)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Apoptosis is associated with caspase-mediated proteolysis of Type I (K18 and K19) cytokeratins. We previously showed a positive association between the levels of tissue polypeptide antigen (TPA), that recognizes cytokeratins K8, K18, and K19 fragments, and induced apoptosis in breast cancer cell lines. The aim of the present study was to evaluate the interrelationships between TPA, steroid receptors, and p53, and their joint prognostic role in node-negative breast cancer patients not treated with adjuvant therapies. Age and pT were also considered since they are known prognostic factors. Five hundred and ninety-nine cases with N- breast cancer were evaluated (median follow-up: 60 months). TPA was measured by an immunoradiometric assay and p53 by an immuno-chemiluminescent assay in tumor cytosol. Multiple correspondence analysis was used to study the associations among variables. Their prognostic role (univariate analysis) and their joint effect (multivariate analysis) on RFS were investigated with Cox regression models. TPA showed a direct association with ER and PgR. Higher p53 values were weakly associated to low values of ER, PgR, and TPA. Younger age was related to low and intermediate values of ER and PgR and to low p53 values, while older age was related to high values of ER. Multivariate analysis showed a significant prognostic impact for pT, age, ER, and TPA. Among the interactions considered clinically relevant, only that between ER and age was found. RFS estimated values were poorer in cases with lower than in those with higher TPA values, both in patients expected to have a poor (pT2, young age, low ER) and a better prognosis (pT1, older age, high ER). From the findings of the present study we can draw the following conclusions: The relationship of TPA with prognosis gives an additional contribution to pT, age, and steroid receptors in N- breast cancer; TPA may be considered the first marker of apoptosis measured with a fully standardized quantitative method in tumor cytosol and could be evaluated in prognostic indexes including markers related to different biological mechanisms.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006318112776
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  • 186
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    Role of specific apoptotic pathways in the restoration of paclitaxel-induced apoptosis by valspodar in doxorubicin-resistant MCF-7 breast cancer cells (2000)
    Springer
    Breast cancer research and treatment 59 (2000), S. 231-244 
    Details
    ISSN: 1573-7217
    Keywords: reversal ; paclitaxel ; resistance ; P-glycoprotein ; breast cancer ; valspodar ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Paclitaxel (Taxol®) kills tumor cells by inducing both cellular necrosis and apoptosis. A major impediment to paclitaxel cytotoxicity is the establishment of multidrug resistance whereby exposure to one chemotherapeutic agent results in cross-resistance to a wide variety of other drugs. For example, selection of MCF-7 breast cancer cells for resistance to doxorubicin (MCF-7ADR cells) results in cross-resistance to paclitaxel. This appears to involve the overexpression of the drug transporter P-glycoprotein which can efflux both drugs from tumor cells. However, MCF-7ADR cells possess a deletion mutation in p53 and have considerably reduced levels of the Fas receptor, Fas ligand, caspase-2, caspase-6, and caspase-8, suggesting that paclitaxel resistance may also stem from a bona fide block in paclitaxel-induced apoptosis in these cells. To address this issue, we examined the ability of the P-glycoprotein inhibitor valspodar to restore paclitaxel accumulation, paclitaxel cytotoxicity, and paclitaxel-induced apoptosis. Compared to drug sensitive MCF-7 cells, MCF-7ADR cells accumulated 〉6-fold less paclitaxel, were approximately 100-fold more resistant to killing by the drug, and were highly resistant to paclitaxel-induced apoptosis. In contrast, MCF-7ADR cells pretreated with valspodar were indistinguishable from drug-sensitive cells in their ability to accumulate paclitaxel, in their chemosensitivity to the drug, and in their ability to undergo paclitaxel-induced apoptosis. Valspodar, by itself, did not affect these parameters. This suggests that the enhancement of paclitaxel toxicity in MCF-7ADR cells involves a restoration of apoptosis and not solely through enhanced drug-induced necrosis. Morever, it appears that changes in the levels/activity of p53, the Fas receptor, Fas ligand, caspase-2, caspase-6, or caspase-8 activity have little effect on paclitaxel-induced cytotoxicity and apoptosis in human breast cancer cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006344200094
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  • 187
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    EORTC 10941: A phase II study of liarozole in postmenopausal patients with ‘Chemotherapy-Resistant’ or ‘Potentially Hormone Sensitive’ metastatic breast cancer (2000)
    Springer
    Breast cancer research and treatment 60 (2000), S. 181-188 
    Details
    ISSN: 1573-7217
    Keywords: aromatase inhibitor ; breast cancer ; liarozole ; retinoic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Liarozole is an imidazole compound that inhibits enzymes involved in steroid hormone aromatisation and retinoid metabolism. The IDBBC branch of the EORTC has performed a series of phase II studies of the agent in four groups of postmenopausal women with metastatic breast cancer. This paper reports the results of the first two groups: ‘Chemotherapy Resistant’ (unrestricted ER status, 1 or 2 prior chemotherapy regimens, 0–2 prior hormonal therapies) and ‘Potentially Hormone Sensitive’ (ER positive or unknown, 1 or 2 prior hormonal therapies with a substantial disease free interval or progression free survival, and no history of chemotherapy for metastatic disease). Liarozole was administered at 150–300 mg orally bid. The objective response rate was 12% in the ‘Chemotherapy Resistant’ group (n=34), and 22% in the ‘Potentially Hormone Sensitive’ group (n=37), with median response durations of 9 and 14 months, respectively. Median time to treatment failure was only 2 months in both groups, due largely to the significant percentage (24%) of patients who ceased treatment following excessive mucocutaneous and gastrointestinal toxicity. This adverse event profile will limit its use in breast cancer. Results of the ‘ER negative’ and ‘Tamoxifen Refractory’ groups will be reported in a future paper.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006398518037
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  • 188
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    Alcohol consumption and risk of breast cancer: a cohort study (2000)
    Springer
    Cancer causes & control 11 (2000), S. 239-247 
    Details
    ISSN: 1573-7225
    Keywords: alcohol ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objectives: To study the association between alcohol consumption and breast cancer risk. Methods: A case–cohort analysis was undertaken within the cohort of 56,837 women who were enrolled in the Canadian National Breast Screening Study (NBSS) and who completed a self-administered dietary questionnaire. (The NBSS is a randomized controlled trial of screening for breast cancer in women aged 40–59 at recruitment.) The cohort was recruited between 1980 and 1985, and during follow-up to the end of 1993 a total of 1469 women in the dietary cohort were diagnosed with biopsy-confirmed incident breast cancer. For comparative purposes a subcohort consisting of a random sample of 5681 women was selected from the full dietary cohort. After exclusions for various reasons the analyses were based on 1336 cases and 5238 noncases. Results: When compared to nondrinkers the adjusted incidence rate ratios (95% confidence intervals) for those consuming 〉 0 and  ≤ 10 g of alcohol/day,  〉 10 and  ≤ 20 g/day,  〉 20 and  ≤thinsp;30 g/day,  〉 30 and  ≤ 40 g/day,  〉 40 and  ≤ 50 g/day, and  〉 50 g/day were 1.01 (0.84–1.22), 1.16 (0.91–1.47), 1.27 (0.91–1.78), 0.77 (0.51–1.16), 1.00 (0.57–1.75), and 1.70 (0.97–2.98), respectively; the associated p value for the test for trend was 0.351. Similar findings were obtained when analyses were conducted separately in the screened and control arms of the NBSS, in premenopausal and postmenopausal women, for screen-detected and interval-detected breast cancer, and by levels of other breast cancer risk factors. Conclusions: The results of this study suggest that alcohol consumption might be associated with increased risk of breast cancer at relatively high levels of intake.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008933824645
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  • 189
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    Patterns of inpatient surgeries for the top four cancers in the United States, National Hospital Discharge Survey, 1988–95 (2000)
    Springer
    Cancer causes & control 11 (2000), S. 497-512 
    Details
    ISSN: 1573-7225
    Keywords: breast cancer ; colon cancer ; lung cancer ; neoplasm ; prostate cancer ; surveillance ; treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: At a time when the population is aging and medical practices are rapidly changing, ongoing surveillance of surgical treatments for cancer is valuable for health services planning. Methods: We used data from the National Hospital Discharge Survey for patients with discharge diagnoses of lung, prostate, female breast, and colorectal cancer during 1988–95 to estimate population-based rates and numbers of inpatient surgical procedures. Results: In 1988–91, rates of lobectomy for lung cancer were significantly higher in males than females. By 1994–95, the male/female differences had largely disappeared due to increasing trends among females and decreasing trends among males. During 1988–95, surgeries on the large intestine for colorectal cancer, including right hemicolectomy and sigmoidectomy, decreased significantly, as did abdominoperineal resections of the rectum. Anterior resections of the rectum increased significantly. Radical prostatectomies for prostate cancer increased from 34,000 in 1988–89 to 104,000 in 1992–93 and then decreased to 87,000 in 1994–95; rates followed a similar pattern. Finally, the number and rates of inpatient mastectomies for female breast cancer decreased over the study period (from 219,000 to 180,000 and from 78.8 to 61.5 per 100,000, respectively). Conclusion: These trends in inpatient surgeries for the major cancers in the US probably reflect changes in disease occurrence and modified treatment recommendations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008944209648
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  • 190
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    A record-based evaluation of induced abortion and breast cancer risk (United States) (2000)
    Springer
    Cancer causes & control 11 (2000), S. 777-781 
    Details
    ISSN: 1573-7225
    Keywords: abortion ; breast cancer ; pregnancy ; women
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective:Previous studies of induced abortion and breast cancer may have been limited by differential reporting of abortion history. We conducted a population-based case–control study to evaluate abortion (both induced and spontaneous) and breast cancer risk. Methods:All study subjects were aged 20–69 years and members of Group Health Cooperative of Puget Sound (GHC). Incident invasive breast cancer cases (n = 138) were identified from the linkage between the GHC enrollment file and the Seattle–Puget Sound SEER Cancer Registry. Controls (n = 252) were randomly selected from GHC enrollment files and matched to cases on age and enrollment period. All subjects had to have been enrolled at GHC for the 2 years preceding diagnosis (cases) or reference (controls) date. The unified medical record of each case was abstracted for pregnancy history, including prior induced and spontaneous abortions, menopause status, height and weight, screening practices, and other risk factors. Results:Compared to all women who had never had an induced abortion, the multivariate adjusted relative risk of breast cancer in women with an induced abortion was 0.9 (95% confidence interval 0.5–1.6). This risk was similar in parous women, and nulliparous women. There was no association between spontaneous abortion and breast cancer risk. Conclusions:These results do not support a relation between induced abortion and breast cancer incidence.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008980804706
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  • 191
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    Shockwave application in calcifying tendinitis of the shoulder – prediction of outcome by imaging (2000)
    Springer
    Archives of orthopaedic and trauma surgery 120 (2000), S. 493-498 
    Details
    ISSN: 1434-3916
    Keywords: Key words Shoulder ; Calcifying tendinitis ; Shock wave ; MRI ; Prediction parameters ; Clinical outcome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This prospective study examined 62 patients (65 shoulders) with chronic courses of calcifying tendinitis of the shoulder before and after low-energy extracorporeal shockwave application (ESWA) in order to identify variables associated with the outcome of this treatment. Before ESWA, radiographs and contrast-enhanced magnetic resonance imaging (MRI) of the affected shoulders were obtained in order to document the size and morphology of the calcifications and the contrast media reactions in areas of interest (deposit, synovia, bursae), respectively. In addition, a clinical evaluation was performed. After ESWA (mean follow-up 18.2 months), clinical evaluations of all 65 shoulders revealed an increase in the Constant score from 44% to 78% (p 〈 0.0001). While size (p = 0.61) and morphology (p = 0.7) of the deposits before ESWA were not associated with the clinical outcome, negative contrast reactions around the deposits (p = 0.0001), synovia (p = 0.0049) and bursae (p 〈 0.01) were associated with improved clinical outcomes. After the total study group was divided into two groups, one with Constant scores ≥ 75% (n = 43) and the other with scores 〈 75% (n = 22), the positive predictive value (ppv), specificity (sp) and sensitivity (se) were determined for the negative reaction around the deposit (ppv: 0.94; sp: 0.95; se: 0.38), synovia (ppv: 0.84; sp: 0.82; se: 0.49) and bursae (ppv: 0.86; sp: 0.86; se: 0.44). In 5 cases (7.7%), surgery of the affected shoulder during the follow-up period was performed. No major side-effects were seen in the study group. In conclusion, our results suggest that in patients with chronic calcifying tendinitis, the absence of contrast enhancement, especially around the deposit, is a strong predictive parameter of a positive clinical outcome of ESWA.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004020000154
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  • 192
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    Electronic Resource
    Chiari type I anomalies in children and adolescents: minimally invasive management in a series of 53 cases (2000)
    Springer
    Child's nervous system 16 (2000), S. 707-718 
    Details
    ISSN: 1433-0350
    Keywords: Keywords Syringomyelia ; Chiari I malformation ; Foramen magnum decompression ; Children ; Scoliosis ; MRI
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The authors studied the role of the sole posterior fossa bony decompression in the management of symptomatic children affected by Chiari type I anomalies. The series in the pediatric literature on this subject were reviewed and compared with that presented in this article. From May 1994 to December 1998, 53 patients (3 months to 26 years) were observed. They were divided into: asymptomatic patients (27), who received no surgical treatment and were only subject to clinical observation; symptomatic patients (brain stem compression 16, syringomyelia 10, including 7 with holocord). All the symptomatic patients were treated with the same surgical approach: bony decompression of posterior fossa with removal of the posterior arch of C-1 and the outer layer of the dura without dural opening. In all 16 (100%) of the 16 patients with brain stem compression the symptoms resolved or improved; in patients with syringomyelia the symptoms were resolved or improved in 94.4% of cases. Two children required further surgery after 13 and 24 months, respectively.This series seems to demonstrate that even a simple extradural surgical approach, with a lower rate of postoperative complications and short stay in hospital, is sufficient to arrest the disease and to improve the symptomatology in a high percentage of cases (97.2%), which is comparable to that achieved with other, more aggressive, procedures.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003810000338
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  • 193
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    Electronic Resource
    Surgical outcome of pediatric hydrocephalus treated by endoscopic III ventriculostomy: prognostic factors and interpretation of postoperative neuroimaging (2000)
    Springer
    Child's nervous system 16 (2000), S. 161-168 
    Details
    ISSN: 1433-0350
    Keywords: Key words Hydrocephalus ; Endoscopic III ventriculostomy ; Outcome ; MRI ; Cine-MRI ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In order to analyze the surgical outcome according to clinical characteristics and to evaluate the correlation between clinical improvement and neuroimaging changes, we retrospectively reviewed 32 children who had undergone endoscopic III ventriculostomy (ETV) from February 1994 to May 1998. There were 15 boys and 17 girls, with a mean age of 5.2 years (range: 1 month to 13 years). The etiology of the hydrocephalus was primary aqueductal stenosis in 18 patients, secondary aqueductal stenosis caused by tumors in 5, IV ventricle outlet obstruction in 5, and hydrocephalus associated with meningomyelocele in 4. The mean duration of follow-up was 19.4 months (range 1–50 months). Overall, surgical outcome was regarded as good in 21 of 29 patients. Surgical outcome was poor in patients younger than 1 year (P〈0.05). Neuroimaging 1 month after ETV showed a decrease in ventricular size in 11 of the 16 patients with good surgical outcomes. Five showed minimal changes only. In patients with good outcomes, ventricular size tended to decrease as time passed. Resolution of periventricular edema, flow void in the III ventricle on T2-weighted axial images, and cine-MR imaging were sensitive indicators of good outcome. We suggest that ETV be considered as a primary treatment option in patients older than 1 year of age with noncommunicating hydrocephalus. In addition, time factors should be taken into consideration when surgical outcome is judged. Changes in ventricular size could not predict surgical outcome completely in themselves. Therefore, a comprehensive postoperative assessment should be made with the help of T2-weighted MRI and cine-MRI.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003810050485
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  • 194
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    Electronic Resource
    Reintitan als Knochenersatzmaterial (2000)
    Springer
    Mund-, Kiefer- und Gesichtschirurgie 4 (2000), S. S504 
    Details
    ISSN: 1434-3940
    Keywords: Schlüsselwörter CAD/CAM ; Knochenersatzmaterial ; MRT ; Qualitätskontrolle ; Titan ; Key words Bone substitute material ; CAD/¶CAM ; MRI ; Quality control ; Titanium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Computer-assisted prefabricated skull implants of pure titanium as a bone replacement material have been used in 22 departments since 1994. Our experience with 104 implants includes clinical aspects (indication; tissue quality; surgical technique; patient guidance), but also geometric and material-specific parameters (acquisition, transfer, and evaluation of CT data; construction; manufacturing; cleaning; postoperative use of radiologic techniques). While the clinical aspects are responsibly defined by the respective surgeon, the geometric and material-specific parameters of individual implants have to comply with the laws on medical products. Therefore, the prospective documentation for each implant includes: helical CT acquisition parameters; geometric data of the computer-based skull model and implant; the cleaning procedure; and the individual marking. Medically specified pure titanium is processed by milling only so that neither purity nor structure is impaired. A specially developed milling technique guarantees the fabrication of all constructed elements down to fine details of 50 μm. Considering the necessary radiologic follow-up of defects after tumor surgery, all patients in our hospital undergo postoperative MRI examination, partly with preoperative documentation as an intraindividual control. Such comprehensive documentation and quality assurance is essential for techniques of prefabricated bone substitution. Hand in hand with scientific research and clinical application, these formal criteria have to be elaborated and fulfilled for the respective techniques. The successful determination of specifically adapted MRI sequences goes even one step further: spin-echo sequences minimize inhomogeneities of the magnetic field induced by the titanium implants and enable accurate postoperative documentation and diagnostics especially in the follow-up after tumor surgery.
    Notes: Zusammenfassung Computergestützt vorgefertigte Schädelimplantate aus Reintitan als Knochenersatzmaterial werden seit 1994 in 22 Kliniken eingesetzt. Die Erfahrungen mit 104 Implantaten umfassen klinische (Indikationsstellung; Implantatlager; Operationstechnik; Patientenführung), aber auch geometrische und materialspezifische Aspekte (CT-Datenakquisition, -transfer und -auswertung; Konstruktion; Fertigung; Reinigung; postoperative Einsatzmöglichkeit bildgebender Verfahren). Während die klinischen Aspekte im Verantwortungsbereich ärztlichen Handelns definiert werden, gilt für die geometrischen und materialspezifischen Aspekte bei individuellen Implantaten das Medizinproduktegesetz. Prospektiv werden entsprechend für jedes Implantat die Spiral-CT-Akquisitionsparameter, die Geometriedaten des rechnerinternen Schädelmodells und des Implantats, das Reinigungsverfahren und die individuelle Kennzeichnung dokumentiert. Medizinisch spezifiziertes Reintitan wird ausschließlich durch Fräsung bearbeitet, sodass weder Reinheit noch Gefüge Änderungen erfahren. Eine eigens entwickelte Frästechnik garantiert die Umsetzung aller konstruierter Elemente bis zu einer Feinheit von 50 μm. Im Hinblick auf die bei tumorbedingten Defekten notwendige bildgebende Verlaufskontrolle werden sämtliche Patienten der eigenen Klinik postoperativ mit MRT untersucht, z. T. mit einer präoperativen Darstellung als intraindividuelle Kontrolle. Eine umfassende Dokumentation und Qualitätssicherung ist für Techniken des vorgefertigten Knochenersatzes unabdingbar. Parallel zur forscherischen Entwicklung und ärztlichen Anwendung müssen diese formalen Kriterien für das jeweilige Verfahren bearbeitet und erfüllt werden. Die erfolgreiche Erarbeitung von eigens adaptierten MRT-Sequenzen geht darüber noch hinaus: Spinechosequenzen minimieren die durch die Titanimplantate erzeugten Feldinhomogenitäten und erlauben eine aussagekräftige postoperative Dokumentation und Diagnostik insbesondere nach Tumoroperationen in der Verlaufsbeobachtung.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00012701
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  • 195
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    Electronic Resource
    Die MRT zur Beurteilung von Schußverletzungen (2000)
    Springer
    Rechtsmedizin 10 (2000), S. 90-95 
    Details
    ISSN: 1434-5196
    Keywords: Schlüsselwörter Geschosse ; Verletzungen ; MRT ; Beurteilung ; Dokumentation ; Keywords Projectiles ; Injuries ; MRI ; Assessment ; Documentation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Law
    Description / Table of Contents: For the assessment of gunshot injuries, conventional X-ray examination, ultrasound and CT examinations are commonly used imaging techniques. With the exception of some authors, there is agreement that projectiles indicate a contraindication for MRI because of artificial imaging side-effects and the potential of secondary dislocation due to ferromagnetism. MRI testing was carried out on 56 projectiles for ferromagnetism and imaging quality in vitro and in pig carcasses with a 0.2 T and a 1.5T-MRI scanner. The image quality was compared to that of a CT scan. Projectiles with ferromagnetic properties can easily be distinguished from non-ferromagnetic ones by pretesting the motion of an projectile of the same type within the magnetic field of the MR scanner. When ferromagnetic projectiles were excluded, MRI yielded the more precise images compared to other imaging techniques. Projectile localization and associated soft tissue injuries were visualized without artifacts in all cases. When ferromagnetism is excluded MRI gives an excellent imaging procedure for the assessment and documentation of gunshot injuries. Therefore this imaging procedure may be also useful for medico-legal investigations.
    Notes: Zur Beurteilung des Ausmaßes von Schußverletzungen und zur Lokalisationsdiagnostik werden allgemein konventionelle Röntgenübersichtsaufnahmen sowie die Sonographie und die Computertomographie angewendet. Mit Ausnahme weniger Autoren wird generell davon ausgegangen, daß Projektile aufgrund der Generierung von Artefakten in der Bildgebung und der Gefahr einer sekundären Fremdkörperdislokation, bedingt durch den Ferromagnetismus, nicht mit der MRT beurteilt werden dürfen. 56 verschiedene Projektile wurden nach entsprechender Vortestung bezüglich ihrer Ferromagnetizität mit je einem 0,2-T- und 1,5-T-MRT-Gerät in vitro und anschließend in Schweinekadavern untersucht. Die Bildqualität wurde mit denen von CT-Bildern verglichen. Die ferromagnetischen Eigenschaften der Projektile können leicht beurteilt werden, indem man Vergleichsgeschosse desselben Typs in das Magnetfeld des MRT-Gerätes legt. Nach Ausschluß der Ferromagnetizität übertrifft die MRT alle anderen bildgebenden Verfahren. In allen Fällen gelang eine exakte Projektillokalisation sowie eine überlegene Darstellung der Weichteilverletzungen. Aufgrund der Ergebnisse ist die MRT, nach Ausschluß von ferromagnetischen Fremdkörpern, ein exzellentes Verfahren zur Beurteilung und Dokumentation von Schußverletzungen. Abhängig von den Fragestellungen kann dieses bildgebende Verfahren auch in der Rechtsmedizin eingesetzt werden.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001940000044
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  • 196
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    Electronic Resource
    Unrealistic Optimism and the Health Belief Model (2000)
    Springer
    Journal of behavioral medicine 23 (2000), S. 367-376 
    Details
    ISSN: 1573-3521
    Keywords: optimistic bias ; Health Belief Model ; breast cancer ; prostate cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Psychology
    Notes: Abstract Why do people fail to engage in positive behaviors which will promote their health and well-being? Researchers addressing this question adopt primarily one of two perspectives, drawing either on theories of health behavior, such as the Health Belief Model (HBM), or on theories of risk perception, such as unrealistic optimism. To overcome this compartmentalization, two studies of cancer screening behavior assessed the extent to which unrealistic optimism occurred in relation to each of the elements of the HBM: severity and curability of cancer and the benefits of, and barriers to, having a screening test. Data were collected using telephone interviews, dialing numbers randomly selected from the telephone directory. In the first study 164 women aged 50 to 70 years responded to questions about breast cancer and screening mammography, while in the second study 200 men aged 45 to 60 years responded to questions about prostate cancer and screening using the prostate specific antigen test. Women had an optimistic bias in relation to breast cancer risk and severity and barriers to having a screening mammogram but not in relation to the benefits of screening. For prostate cancer, there was an optimistic bias for all HBM variables: risk and severity of prostate cancer and barriers to and benefits of screening. It was concluded that unrealistic optimism is broader than perceived risk, being evident for all elements of the HBM.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1005500917875
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  • 197
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    Electronic Resource
    Breast Cancer in Men: Emasculation by Association? (2000)
    Springer
    Journal of clinical psychology in medical settings 7 (2000), S. 91-97 
    Details
    ISSN: 1573-3572
    Keywords: breast cancer ; breast cancer in men ; male breast carcinoma ; breast cancer treatment ; psychological effects of cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The occurrence of breast cancer in men is rare in comparison to women. Public knowledge that men can get breast cancer and of male breast self-examination are lacking. Research in the course and treatment of breast cancer in men is needed. Men generally present in more advanced stages of breast cancer than women, and have a poorer prognosis. In this article, the epidemiology, common symptoms, diagnostic methods, and current treatment of breast cancer in men are described. Gender differences in presentation and course of illness are discussed. Additionally, the psychological implications of breast cancer for male gender roles and masculine identity are explored. Directions for further investigation are given. Treatment providers are encouraged to educate themselves and their male patients on breast cancer in men and male breast examination techniques so that this disease may be identified earlier in its course and survival rates improved.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009553613564
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  • 198
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    Electronic Resource
    Multivariate Genetic Analysis of Brain Structure in an Extended Twin Design (2000)
    Springer
    Behavior genetics 30 (2000), S. 311-319 
    Details
    ISSN: 1573-3297
    Keywords: Extended twin study ; methodology ; structural equation modeling ; intermediate phenotype ; MRI
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Psychology
    Notes: Abstract The hunt for genes influencing behavior may be aided by the study of intermediate phenotypes for several reasons. First, intermediate phenotypes may be influenced by only a few genes, which facilitates their detection. Second, many intermediate phenotypes can be measured on a continuous quantitative scale and thus can be assessed in affected and unaffected individuals. Continuous measures increase the statistical power to detect genetic effects (Neale et al., 1994), and allow studies to be designed to collect data from informative subjects such as extreme concordant or discordant pairs. Intermediate phenotypes for discrete traits, such as psychiatric disorders, can be neurotransmitter levels, brain function, or structure. In this paper we conduct a multivariate analysis of data from 111 twin pairs and 34 additional siblings on cerebellar volume, intracranial space, and body height. The analysis is carried out on the raw data and specifies a model for the mean and the covariance structure. Results suggest that cerebellar volume and intracranial space vary with age and sex. Brain volumes tend to decrease slightly with age, and males generally have a larger brain volume than females. The remaining phenotypic variance of cerebellar volume is largely genetic (88%). These genetic factors partly overlap with the genetic factors that explain variance in intracranial space and body height. The applied method is presented as a general approach for the analysis of intermediate phenotypes in which the effects of correlated variables on the observed scores are modeled through multivariate analysis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026501501434
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  • 199
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    Electronic Resource
    Adolescent Daughters of Mothers with Breast Cancer: Impact and Implications (2000)
    Springer
    Clinical social work journal 28 (2000), S. 183-195 
    Details
    ISSN: 1573-3343
    Keywords: adolescent ; mother ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract While the literature supports the view that a parent's illness will have an impact on a child, less specific attention has been given to the impact of a mother's breast cancer on her adolescent daughter. In this paper, clinical vignettes derived from interviews with adolescent daughters (ages 12–19) living with mothers who have breast cancer are presented to illustrate some of the concerns daughters have about themselves and their mother's illness. The daughters express anxiety about changes in family roles, but seem more concerned about the potential loss of the mother/daughter relationship. They describe their fears of recurrence of the disease as well as getting the disease themselves. The girls also demonstrate great strength; resilience and hope in the face of the challenges presented by the changes in their lives. Girls who had mothers die of the disease are not included in this article. Implications for treatment are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1005106301713
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  • 200
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    Electronic Resource
    Preclinical MRI Experience in Imaging Angiogenesis (2000)
    Springer
    Cancer and metastasis reviews 19 (2000), S. 39-43 
    Details
    ISSN: 1573-7233
    Keywords: angiogenesis ; MRI ; permeability ; in vivo imaging ; hypoxia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Magnetic resonance imaging (MRI) provides a range of non-invasive measures for visualization of tumor angiogenesis in the clinic as well as in experimental tumor models. MRI methods were developed for assessment of spatial and temporal changes in perfusion, blood volume fraction, vascular permeability, vascular function, vascular maturation, vessel diameter and tortuosity. Molecular targeted contrast agents were used for mapping specific markers of neovasculature. These approaches were applied for analysis of a number of regulatory mechanisms controlling tumor angiogenesis and for preclinical evaluation of tumor response to antiangiogenic agents.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026583911941
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