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  • 2000-2004  (165)
  • 1970-1974  (454)
  • Ultrastructure  (478)
  • breast cancer
  • 1
    Electronic Resource
    Electronic Resource
    Identification of High-Risk Breast Cancer Patients from Genetic Changes of Their Tumors (2000)
    Springer
    Surgery today 30 (2000), S. 516-522 
    Details
    ISSN: 1436-2813
    Keywords: Key Words: genetic changes ; prognostic factor ; breast cancer ; amplification ; loss of heterozygosity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: ERBB2 , INT2, and MYC genes, in 131 patients with breast carcinoma, 49 of whom had lymph node involvement, but none of whom had distant metastases. Among the several chromosome arms tested, LOH at 17q was correlated with lymph node metastasis. Amplification of the ERBB2, MYC, and INT2 genes was found more frequently in tumors from patients with lymph node metastases than in tumors from those without lymph node metastases. Univariate analysis demonstrated that LOH at 17q and INT2 amplification were factors influencing disease-free survival (DFS). A multivariate analysis was performed on 89 tumors that were able to be evaluated for both LOH at 17q and INT2 amplification, and the results showed that patients who had tumors with these genetic changes were more likely to have a poor prognosis. The findings of this study suggest that investigating genetic changes, in addition to conventional clinicopathologic factors, may contribute to defining groups of breast cancer patients with differences in prognosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s005950070118
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  • 2
    Electronic Resource
    Electronic Resource
    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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  • 3
    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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  • 4
    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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  • 5
    Electronic Resource
    Electronic Resource
    An Analysis of Unicellular Mass Transfer Using a Microfabricated Experimental Technique (2000)
    Springer
    Biomedical microdevices 2 (2000), S. 305-316 
    Details
    ISSN: 1572-8781
    Keywords: membranes ; breast cancer ; oncology ; cell column regulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract Using microfabrication technology, we have developed a new experimental apparatus and technique which allow isolation of individual cells and which facilitate the study of kinetic volume changes and membrane permeability. The key component of the apparatus is a microdiffusion chamber which was constructed using silicon microfabrication technology and standard photolithography. The central unit of the chamber is a 1 μ m thick silicon nitride membrane with a center hole on the order of 2–3 μ m in diameter. The device is novel in its analysis of a single cell, instead of the traditional array of cells, and its avoidance of the damage artifacts and computational difficulties which are inherent in other, commonly used methods of cellular analysis. The device is used in conjunction with a predictive computer model which simulates the response of the entire membrane or a portion of the membrane to various permeant and impermeant concentrations. This study introduces the apparatus and the model, and illustrates the effectiveness of the new procedure by determining several membrane permeability coefficients for HBL-100 (healthy human breast line). The empirical data and theoretical data were combined to yield a water permability (L p) of 1.1 ± 0.5μ m/(min-atm) (mean ± 1 standard deviation) (N= 5) during the uncoupled transport of water at 22 ±C. In the presence of 6 M glycerol, the water permeability (L p), permeability coefficient (P S), and the reflection coefficient (σS) were determined to be 2.0 ± 0.63 μ m/(min-atm), 2.7E-5 ± 6.1E-6 cm-sec-1, and 0.76 ± 0.5 (N = 6). No previous values of these coefficients could be found for HBL-100 cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009959323022
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  • 6
    Electronic Resource
    Electronic Resource
    Comparative study of clinical, pathological and biological characteristics of symptomatic versus asymptomatic breast cancers (2000)
    Springer
    Annals of oncology 11 (2000), S. 581-586 
    Details
    ISSN: 1569-8041
    Keywords: biological/pathological characteristics ; breast cancer ; prognosis ; progression ; symptomatic/asymptomatic patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:It is well known that mammographic screening reducesbreast cancer mortality. One possible explanation for this effect is thatscreening makes it possible to detect smaller breast cancers with fewerinvolved nodes, but another hypothesis is that some screening-detected tumorsare in a pathologically and biologically different phase of evolution fromthose that are detected clinically. The aim of the present study was tocompare the biological, pathological and clinical characteristics ofsymptomatic vs. asymptomatic breast cancers. Patients and methods:The study considers a series of 1916consecutive patients who underwent surgery for stage I and II infiltratingbreast cancer at Verona hospitals after having undergone ultrasound andmammography (at least one of which was positive). They were divided into twogroups on the basis of why they decided to undergo the imaging examinations:group A refers to the 1247 patients with a palpable lump, and group B to the616 who were asymptomatic. Results:The patients in group A were older, and had larger tumorsand a higher percentage of positive nodes than those in group B; they also hadsignificantly higher grade tumors, higher Ki-67 levels, and a higherpercentage of ER and PgR negative and c-erbB-2 positive tumors (allof the P-values were significant). A logistic regression analysisadjusted for tumor diameter and age showed a reduction in the significance ofeach of the considered variables, but all of them remained significantlyassociated with the modality of diagnosis except ER, PgR andc-erbB-2. Conclusions:Our results suggest that asymptomatic tumors arebiologically different from their clinically presenting counterparts, thusconfirming the hypothesis that progression towards greater malignancy mayoccur during the natural history of breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008320317114
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  • 7
    Electronic Resource
    Electronic Resource
    Combined 4-hydroxy-ifosfamide and vinorelbine treatment in established and primary human breast cell cultures (2000)
    Springer
    Annals of oncology 11 (2000), S. 587-594 
    Details
    ISSN: 1569-8041
    Keywords: 4-OH-IF ; breast cancer ; drug combination ; human cell lines ; primary cultures ; VNB
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Vinorelbine and ifosfamide are active drugs againstbreast cancer, but the best treatment schedule has yet to be defined bypreclinical or clinical studies. The antitumor activity of4-hydroxy-ifosfamide (4-OH-IF), the active form of ifosfamide, and vinorelbine(VNB) and their interaction were investigated in two established breast cancercell lines (MCF-7 and BRC-230) and in 10 primary breast cancer cultures. Materials and methods:Cytotoxic activity was evaluated by ahighly efficient clonogenic assay (HECA). The median-effect principle wasapplied to evaluate synergistic and antagonistic interactions and thecorresponding combination index values were calculated. Cell cycleperturbations were analysed by flow cytometry. Results:In MCF-7 and BRC-230 cell lines the sequence VNB for 4hours followed by 4-OH-IF for 24 hours produced an antagonistic effect.Conversely, the inverse sequential scheme, 4-OH-IF → VNB providedsynergistic effects on both cell lines. The synergism was associated with astrong block in the G2-M phase. Synergistic activity of 4-OH-IF → VNBsequence was confirmed in 7 of 10 primary breast cancercultures. Conclusions:In conclusion, the sequence 4-OH-IF → VNBappeared to be the most effective scheme both in established cell lines andin primary breast cancer cultures.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008340902093
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  • 8
    Electronic Resource
    Electronic Resource
    Delayed adjuvant tamoxifen: Ten-year results of a collaborative randomized controlled trial in early breast cancer (TAM-02 trial) (2000)
    Springer
    Annals of oncology 11 (2000), S. 515-519 
    Details
    ISSN: 1569-8041
    Keywords: adjuvant treatment ; breast cancer ; tamoxifen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aim:Immediate adjuvant tamoxifen reduces disease recurrence andimproves survival in patients with early breast cancer. However, is it toolate to administer tamoxifen to patients who have already undergone treatment,but were unable to benefit from this adjuvant therapy? The French NationalCancer Centers (FNCLCC) have investigated the efficacy of delayed tamoxifenadministration in a randomized controlled trial. Patients and methods:From September 1986 to October 1989, womenwith primary breast cancer, who had undergone surgery, radiotherapy, and/orreceived adjuvant chemotherapy but not hormone therapy more than two yearsearlier, were randomized to receive either 30 mg/day tamoxifen or notreatment. The 10-year disease-free and overall survival rates of the twogroups of patients and of various subgroups were determined according to theKaplan–Meyer method and compared by the log-rank test. Results:This intention-to-treat analysis comprised 250 women inthe tamoxifen group and 244 in the control group. Patient characteristics(age, T stage, number of positive nodes, receptor status, and interval sincetumor treatment) were comparable in both groups. Delayed adjuvant tamoxifensignificantly improved overall survival only in node-positive patients and inpatients with estrogen receptor-positive (ER+) or progesteronereceptor-positive (PR+) tumors. Disease-free survival, however, wassignificantly improved in the global population and in several patientsubgroups (node-positive, ER+, PR+). Patients in whom the interval betweenprimary treatment and delayed adjuvant tamoxifen was greater than five yearsalso had significantly improved disease-free survival. Conclusions:Overall and disease-free survival results indicatethat delayed adjuvant tamoxifen administration (30 mg/day) is justified inwomen with early breast cancer, even if this treatment is initiated two ormore years after primary treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008321415065
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  • 9
    Electronic Resource
    Electronic Resource
    Tumor lysis syndrome following hemi-body irradiation for metastatic breast cancer (2000)
    Springer
    Annals of oncology 11 (2000), S. 1349-1351 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; radiotherapy ; tumor lysis syndrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Tumor lysis syndrome (TLS) is a rare serious acute complication of cancertherapy, reported mainly following chemotherapy in patients with large tumorload and chemosensitive disease. These are mainly patients with non-Hodgkin'slymphoma, leukemia and rarely in solid tumors. It is less frequently describedafter radiotherapy for lymphoid and hematological malignancies. TLS followingradiotherapy for solid tumors is a very rare complication. In thisreport/review we describe a seventy-three-year-old male patient withprogressive metastatic carcinoma of the breast to the lungs, liver and bone.He was referred for radiotherapy because of generalized bony pains. Thepatient was planned for sequential hemi-body irradiation starting with themore symptomatic upper half body. After premedication, he was given 8.5 Gy tothe mid point at the maximum chest separation with anterior lung attenuatorlimiting uncorrected lung dose to 6.15 Gy. A further 3.5 Gy electron boost tothe fungating breast tumor was given to the 100%. Forty-eight hours after irradiation he developed hyperkalemia,hyperphosphatemia, hyperuricemia, hypocalcemia and renal failure. Theseclinical and biochemical changes are typical of tumor lysis syndrome (TLS).Despite hydration, and treating the hyperuricemia, the patient developed comaand died eight days after irradiation. The prophylaxis and management of TLS and in high-risk patients aredescribed to avoid this frequently fatal complication.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008347226743
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  • 10
    Electronic Resource
    Electronic Resource
    ErbB2 status and the benefit from two or five years of adjuvant tamoxifen in postmenopausal early stage breast cancer (2000)
    Springer
    Annals of oncology 11 (2000), S. 1545-1550 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; erbB2 ; HER-2/neu ; tamoxifen ; therapy resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aim:We aimed to study the importance of erbB2 status in earlystage postmenopausal breast cancer for patients who participated in a trialof five vs. two years of adjuvant tamoxifen. Patients and methods:We analysed the erbB2 status of the tumoursfrom 577 patients participating in the trial, either by a DNA amplificationassay (n = 181) or by measurement of the protein level with flowcytometry (n = 396). Results:ErbB2 was overexpressed or gene amplified in 102 of thepatients (18%). Overall, erbB2-positive patients had a significantlylower recurrence-free probability than others, 62% at five years ascompared to 83%, and showed a significantly decreased breast cancersurvival rate (P = 0.0007). ErbB2 status was significantlyassociated with recurrence and death in Cox multivariate analysis, adjustingfor nodal status, tumour size and estrogen receptor status. The relative riskof recurrence (RR) for five vs. two years of tamoxifen was analysed inrelation to erbB2 status for patients still disease-free two years aftersurgery. Whereas erbB2-negative patients showed significant benefit fromprolonged treatment (RR = 0.62, 95% confidence interval (95%CI): 0.42–0.93), no benefit was evident for erbB2-positive patients (RR= 1.1, 95% CI: 0.41–3.2). When the same analysis was restrictedto ER-positive patients a similar difference in relative hazard was obtainedbut the difference was not strictly significant (P = 0.065). Conclusions:For early stage breast cancer patients treated withadjuvant tamoxifen, overexpression of erbB2 is an independent marker of poorprognosis. The results suggest that overexpression decreases the benefit fromprolonged tamoxifen treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008313310474
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  • 11
    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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  • 12
    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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  • 13
    Electronic Resource
    Electronic Resource
    The need for speed. II. Myelin in calanoid copepods (2000)
    Springer
    Journal of comparative physiology 186 (2000), S. 347-357 
    Details
    ISSN: 1432-1351
    Keywords: Key words Crustacean ; Sensorimotor ; Ultrastructure ; Multilamellar sheath ; Myelinated axons
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Speed of nerve impulse conduction is greatly increased by myelin, a multi-layered membranous sheath surrounding axons. Myelinated axons are ubiquitous among the vertebrates, but relatively rare among invertebrates. Electron microscopy of calanoid copepods using rapid cryofixation techniques revealed the widespread presence of myelinated axons. Myelin sheaths of up to 60 layers were found around both sensory and motor axons of the first antenna and interneurons of the ventral nerve cord. Except at nodes, individual lamellae appeared to be continuous and circular, without seams, as opposed to the spiral structure of vertebrate and annelid myelin. The highly organized myelin was characterized by the complete exclusion of cytoplasm from the intracellular spaces of the cell generating it. In regions of compaction, extracytoplasmic space was also eliminated. Focal or fenestration nodes, rather than circumferential ones, were locally common. Myelin lamellae terminated in stepwise fashion at these nodes, appearing to fuse with the axolemma or adjacent myelin lamellae. As with vertebrate myelin, copepod sheaths are designed to minimize both resistive and capacitive current flow through the internodal membrane, greatly speeding nerve impulse conduction. Copepod myelin differs from that of any other group described, while sharing features of every group.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003590050435
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  • 14
    Electronic Resource
    Electronic Resource
    Immunohistochemical localization of mitogen-activated protein kinase (MAPK) family and morphological changes in rat heart after ischemia-reperfusion injury (2000)
    Springer
    Medical electron microscopy 33 (2000), S. 74-81 
    Details
    ISSN: 1437-773X
    Keywords: Key words Mitogen-activated protein kinase (MAPK) ; Ischemia reperfusion injury ; Heart ; Ultrastructure ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The mitogen-activated protein kinase (MAPK) family is considered to be activated by stress, but the role of the MAPK family is still unknown in cardiac pathology. In the present study, not only the localization of MAPKs such as the extracellular responsive kinase (ERK), c-jun N-terminal kinase (JNK), and p38 MAPK (p38), but also ultrastructural changes were investigated in the ischemia-reperfusion model of Wistar rats. At 5, 10, 30, 60, and 180 min reperfusion after 30 min ischemia by occluding the coronary artery, the expression of these MAPKs was increased in blood vessels and cardiomyocytes by Western blotting and immunohistochemical methods. In addition, after ischemia reperfusion, various ultrastructural changes such as decreased glycogen granules, mitochondrial swelling, and myolysis were observed in the blood vessels and cardiomyocytes. These results suggest that protein kinases may regulate numerous biological processes, including the regulation of contraction and ion transport.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s007950070005
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  • 15
    Electronic Resource
    Electronic Resource
    An immunohistochemical and ultrastructural study of a follicle-stimulating hormone-secreting gonadotroph adenoma occurring in a 10-year-old girl (2000)
    Springer
    Medical electron microscopy 33 (2000), S. 25-31 
    Details
    ISSN: 1437-773X
    Keywords: Key words Gonadotroph adenoma ; FSH ; Childhood ; Ultrastructure ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Female gonadotroph adenomas with endocrinological symptoms are uncommon. Six cases of such adenomas have been reported in the literature: two were girls who presented with precocious puberty and four were premenopausal women with accompanying multiple ovarian cysts. We describe here a 10-year-old Japanese girl with a gonadotroph macroadenoma and present detailed morphological findings of the tumor. The patient's chief complaints were nausea, abdominal distention, and abdominal pain. Abdominopelvic ultrasonography and magnetic resonance imaging (MRI) revealed bilateral multiple ovarian cysts. Endocrinological assays showed elevated serum follicle-stimulating hormone (FSH) (33.7 mIU/ml) and estradiol (3840 pg/ml). MRI of the head showed a large pituitary tumor. Two transsphenoidal operations and subsequent radiation therapy were performed. Immunohistochemically, more than half the tumor cells were positive for anti-FSH-β monoclonal antibody. Ultrastructurally, the tumor cells exhibited a fairly uniform picture of rounded cells. Their nuclei were slightly irregular and contained heterochromatin, and their cytoplasm contained many round, dense core granules, measuring 140–260 nm in diameter, together with well-developed organelles. An in vitro study showed that the tumor cells in primary culture produced FSH (1089.0 mIU/ml). To our knowledge, this is the first immunohistochemical and ultrastructural study of an FSH-secreting gonadotroph adenoma occurring in childhood.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s007950000004
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  • 16
    Electronic Resource
    Electronic Resource
    Ultrastructural evaluation of apoptosis induced by Helicobacter pylori infection in human gastric mucosa: novel remarks on lamina propria mucosae (2000)
    Springer
    Medical electron microscopy 33 (2000), S. 82-88 
    Details
    ISSN: 1437-773X
    Keywords: Key words Apoptosis ; Helicobacter pylori ; Fibroblasts ; Smooth muscle cells ; Ultrastructure ; Gastroduodenal ulcer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It has been considered that Helicobacter pylori (H. pylori) infection is a major cause of human gastritis and gastroduodenal ulcers (G-DU). Many investigations of the relationship between H. pylori and apoptosis have been reported recently. However, these studies focused mostly on epithelium, using the TUNEL method. In the present study, we evaluated by electron microscopy the occurrence of apoptosis in the mesenchymal cells of lamina propria mucosae infected with H. pylori. Gastric biopsy specimens from 37 H. pylori-infected G-DU patients and 8 noninfected volunteers were examined with both light and electron microscopy and analyzed by the TUNEL method. The TUNEL method showed no significant difference between H. pylori-infected and noninfected cases. In contrast, electron microscopy revealed significant numbers of apototic fibroblasts and smooth muscle cells in H. pylori-infected lamina propria mucosae, with a diminished number of collagen fibers in surrounding areas. These areas showed edematous changes histopathologically. These results indicated that H. pylori infection induces apoptosis of fibroblasts and smooth muscle cells in lamina propria, with decrease in the numbers of collagen fibers, suggesting that these alterations may be affected by exaggerate acid secretion, decrease mucus protecting factors, and result in ulcer formation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s007950070006
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  • 17
    Electronic Resource
    Electronic Resource
    Ciliogenesis and ciliary abnormalities (2000)
    Springer
    Medical electron microscopy 33 (2000), S. 109-114 
    Details
    ISSN: 1437-773X
    Keywords: Key words Ciliogenesis ; Ciliated cell ; Abnormal cilia ; Basal body ; Ultrastructure ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cilia are motile processes extending from the basal bodies, playing important roles in the mucociliary clearance in the respiratory tract and the transport of the ovum from the ovary to the uterus in mammals. Ciliogenesis is divided into four stages: (1) duplication of centrioles; (2) migration of centrioles to the apical cell surface to become basal bodies; (3) elongation of cilia containing the axoneme; and (4) formation of accessory structures of basal bodies. The orderly course of ciliogenesis appears to be disturbed by various internal and external factors and, as a result, various unusual forms of the ciliary apparatus develop in the cell. Inhibition of basal body migration results in development of intracytoplasmic axonemes, cilia within periciliary sheaths, and intracellular ciliated cysts. Swollen cilia and the bulging type of compound cilia are formed during ciliary budding and elongation. This review also discusses the origin, composition, and function of the centriolar precursor structures.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s007950000009
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  • 18
    Electronic Resource
    Electronic Resource
    Abnormal elastic system fibers in fibrotic human liver (2000)
    Springer
    Medical electron microscopy 33 (2000), S. 135-142 
    Details
    ISSN: 1437-773X
    Keywords: Key words Elastic system fiber ; Ultrastructure ; Fibrotic human liver ; Oxytalan fiber ; Elaunin fiber
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The network of elastic system fibers in human fibrotic liver was investigated by histological methods, immunohistochemical staining, and electron microscopy. Type III collagen was seen not only in regions of portal fibrosis but also in the sinusoidal wall. However, elastic system fibers were not found in the Disse space of the sinusoidal wall. Elastic system fibers including oxytalan, elaunin, and elastic fibers were found successively in the course of elastogenesis. A few normal oxytalan fibers and abnormal oxytalan fibers were observed in the periportal tracts. Few normal elaunin and abnormal elaunin fibers were observed in regions of portal fibrosis but not in the surrounding margin. Elastic fibers, only in scarce amounts, were observed around the portal veins in the case of chronic active hepatitis but not in acute hepatitis. Abnormal oxytalan fibers were seen as a bundle of wavelike microfibrils and had an irregular arrangement. Abnormal elaunin fibers were not associated with bundles of microfibrils. Abnormal elaunin fibers in large amounts were found interspersed with spiraled collagen, which most likely indicates that the oxytalan fibers degenerated in the course of elastogenesis. Thus, in a fibrotic liver it is possible that synthesis of normal elaunin and elastic fibers does not occur or that the quantity of such fibers synthesized may be small because of the effect of the degenerated oxytalan fibers. As a characteristic of liver fibrosis, the composition of abnormal elastic system fibers and spiraled collagen differs from that in other fibrotic organs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s007950000013
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  • 19
    Electronic Resource
    Electronic Resource
    Adenoid basal carcinoma of the uterine cervix: a case report with ultrastructural findings (2000)
    Springer
    Medical electron microscopy 33 (2000), S. 241-245 
    Details
    ISSN: 1437-773X
    Keywords: Key words Adenoid basal carcinoma ; Uterine cervix ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Adenoid basal carcinoma of the uterine cervix is a rare tumor with a favorable prognosis. A case of adenoid basal carcinoma (ABC) of the uterine cervix was studied using light and electron microscopy. The patient was a 74-year-old Japanese woman who had undergone hysterectomy due to cervical intraepithelial neoplasia 3. Incidentally, ABC was found in the resected uterus. The tumor cells made small nests and infiltrated the cervical portion of the uterus. In the nests, glands, cribriform patterns with glandlike structures, and squamous differentiation were seen. Immunohistochemically, the glandlike structures were positive for laminin and type IV collagen. Ultrastructurally, the tumor cells had irregular nuclei, scanty cytoplasm, and cribriform patterns in which glandlike structures were covered with basal lamina. No myoepithelial differentiation of the tumor cells was seen. These findings suggest a similarity between adenoid basal carcinomas and adenoid cystic carcinomas. Furthermore, both tumors are considered to originate in the reserve cells of the uterine cervix. Because their outcomes are different, they should be distinguished from each other.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s007950000024
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  • 20
    Electronic Resource
    Electronic Resource
    Variation among giant rice bodies: report of four cases and their clinicopathological features (2000)
    Springer
    Skeletal radiology 29 (2000), S. 525-529 
    Details
    ISSN: 1432-2161
    Keywords: Key words Giant rice body ; Ultrastructure ; Immunohistochemistry ; Histogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Objective: To report four cases of rice bodies (RBs) showing remarkable size variations and discuss their pathogenesis. Design and patients: Based on analysis of the clinical data, we speculate on the pathogenesis of RBs using immunohistochemical and ultrastructural methods. The patients comprised three men and one woman, three with RBs in the subacromial bursae and one in the wrist synovial sheath, aged 28 (woman), 44, 50 and 81 (wrist) years, respectively. Results: There were no particular differences in clinical data among the patients. T2-weighted MR imaging was very useful for diagnosis of the RBs, allowing their clear delineation from the bursal fluid. The RBs consisted of a layered protein- aceous substance with vague targetoid cut surfaces. Much fibrin and a lesser amount of collagen fibers were recognized together with various mononuclear cells, which were few in number and predominantly T cells. The bursae and synovial sheath had multiple fibrinoid spheroids at the luminal surface. Conclusion: Fibrinoid nodular deposits probably became detached, forming the nuclei of RBs and growing to a giant RB 65 mm in diameter.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002560000258
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  • 21
    Electronic Resource
    Electronic Resource
    Ultrastructure and molecular histology of rabbit hind-limb collateral artery growth (arteriogenesis) (2000)
    Springer
    Virchows Archiv 436 (2000), S. 257-270 
    Details
    ISSN: 1432-2307
    Keywords: Key words Arteriogenesis ; Collateral vessels ; Ultrastructure ; Cell adhesion molecules
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Previous studies in the canine heart had shown that the growth of collateral arteries occurs via proliferative enlargement of pre-existing arteriolar connections (arteriogenesis). In the present study, we investigated the ultrastructure and molecular histology of growing and remodeling collateral arteries that develop after femoral artery occlusion in rabbits as a function of time from 2 h to 240 days after occlusion. Pre-existent arteriolar collaterals had a diameter of about 50 µm. They consisted of one to two layers of smooth muscle cells (SMCs) and were morphologically indistinguishable from normal arterioles. The stages of arteriogenesis consisted of arteriolar thinning, followed by transformation of SMCs from the contractile- into the proliferative- and synthetic phenotype. Endothelial cells (ECs) and SMCs proliferated, and SMCs migrated and formed a neo-intima. Intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) showed early upregulation in ECs, which was accompanied by accumulation of blood-derived macrophages. Mitosis of ECs and SMCs started about 24 h after occlusion, whereas adhesion molecule expression and monocyte adhesion occurred as early as 12 h after occlusion, suggesting a role of monocytes in vascular cell proliferation. Treatment of rabbits with the pro-inflammatory cytokine MCP-1 increased monocyte adhesion and accelerated vascular remodeling. In vitro shear-stress experiments in cultured ECs revealed an increased phosphorylation of the focal contacts after 30 min and induction of ICAM-1 and VCAM-1 expression between 2 h and 6 h after shear onset, suggesting that shear stress may be the initiating event. We conclude that the process of arteriogenesis, which leads to the positive remodeling of an arteriole into an artery up to 12 times its original size, can be modified by modulators of inflammation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050039
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  • 22
    Electronic Resource
    Electronic Resource
    Ganglioglioma with a tanycytic ependymoma as the glial component (2000)
    Springer
    Acta neuropathologica 99 (2000), S. 310-316 
    Details
    ISSN: 1432-0533
    Keywords: Key words Ganglioglioma ; Ependymoma (tanycytic variant) ; Neurofibrillary tangle ; Immunohistochemistry ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We studied a cystic ganglioglioma (GG) located in the right frontal lobe of the brain. Interestingly, the fibrillary spindle glial cells were often arranged in a fascicular pattern, and the generally uniform, round-to-oval delicate nuclei appeared to resemble those of ependymoma; and the neoplastic neurons often contained neurofibrillary tangles (NFTs). The glial component was positive for glial fibrillary acidic protein and occasionally contained granular or microvesicular structures positive for epithelial membrane antigen. Ultrastructural investigation revealed that the glial cells were ependymal in nature; intracytoplasmic lumina and intercellular microrosettes lined with cilia and microvilli, as well as long zonulae adherentes, were evident. In addition, chromogranin A-positive granular staining, neurosecretory-granule-like structures, and parallel arrays of microtubules were sometimes associated with the blood vessels. We considered the present case to be an unusual example of GG with an ependymoma, more precisely a tanycytic ependymoma, as the glial component; to our knowledge, the existence of ependymoma as the main glial component of this particular tumor has not been described before. The occurrence of NFTs, which has been reported in several cases of GG, was an additional, unusual feature.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00007443
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  • 23
    Electronic Resource
    Electronic Resource
    Eosinophilic inclusions in ependymoma represent microlumina: a light and electron microscopic study (2000)
    Springer
    Acta neuropathologica 99 (2000), S. 214-218 
    Details
    ISSN: 1432-0533
    Keywords: Key words Eosinophilic inclusion body ; Inclusion ¶body ; Ependymoma ; Microlumina ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A study was undertaken to determine the pathological significance of previously unrecognized intracytoplasmic eosinophilic inclusions (IEIs) in ependymoma. The study group consisted of 58 ependymomas, all of which were pathologically characterized and graded according to the 1993 WHO classification. Electron microscopic studies were performed in 16 cases. The study showed that 33 (57%) ependymomas had IEIs and that in 8 cases these were abundant. Round and eosinophilic, their sizes varied from 10 μm to a tiny dot. Similar eosinophilic bodies were also observed between tumor cells. The inclusions were weakly PAS positive. On immunostains, IEIs were frequently positive for glial fibrillary acidic protein, less often for S-100 protein, and for epithelial membrane protein and CAM 5.2. They were negative for AE1/AE3, carcinoembryonic antigen and Ber-EP4. Ultrastructurally, IEIs represented intracytoplasmic lumens containing microvilli and cilia. These microlumina also frequently contained granulo-tubular materials. With reference to tumor subtypes, IEIs occurred most frequently in ordinary and clear cell ependymomas. IEIs were also present in 4 of 6 anaplastic ependymomas studied. In conclusion, IEIs represent microlumina and occur in more than a half of ependymomas including malignant examples. Their finding is a helpful diagnostic feature of ependymoma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00007427
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  • 24
    Electronic Resource
    Electronic Resource
    Ultrastructure of the normal adult human female prostate gland (Skene’s gland) (2000)
    Springer
    Anatomy and embryology 201 (2000), S. 51-61 
    Details
    ISSN: 1432-0568
    Keywords: Key words Female prostate (Skene gland) ; Ultrastructure ; Secretory (luminal) cells ; Basal (reserve) cells ; Intermediary cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The predominant cells of female prostatic glands lining their lumen were found to be tall cylindrical secretory cells with short stubby microvilli, protuberances of the apical cytoplasm, and with bleb formation. Abundant secretory vacuoles and granules, rough endoplasmic reticulum, developed Golgi complexes and numerous mitochondria are characteristic of their active secretory configuration with apocrine (apical blebs) and merocrine (secretory vacuoles and granules) type of secretion. Basal (reserve) cells were seen to be located between the secretory (luminal) cells and the basement membrane. Their ground cytoplasm is dense with rough endoplasmic reticulum and mitochondria. Their nuclei, unlike those of secretory cells, possess more peripheral condensed chromatin, denser dispersed chromatin and sporadic nucleoli. Besides the two basic types of mature prostatic cells intermediary cells were also seen, located between the basal and secretory cells or in their close vicinity. Their cytoplasm exhibits numerous profiles of rough endoplasmic reticulum and free ribosomes. Secretory vacuoles and granules were mostly practically absent (type 1 intermediary cells) so that they resembled basal (reserve) cells. In some of them, however, as in secretory cells, such secretory elements do gradually appear (type 2 intermediary cells). The finding of intermediary cells in the lining of prostatic glands supports the role of basal (reserve) cells in the renewal of cells in glands of the female prostate. The first ultrastructural analysis of the normal female prostate performed by transmission electron microscopy showed that, as in the postpubertal male, the prostatic glands in the adult female display mature secretory and basal cells. The results of the presented study further corroborate the contemporary concept of the female prostate as a functional genitourinary organ.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/
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  • 25
    Electronic Resource
    Electronic Resource
    Microglial cells are the driving force in fibrillar plaque formation, whereas astrocytes are a leading factor in plaque degradation (2000)
    Springer
    Acta neuropathologica 100 (2000), S. 356-364 
    Details
    ISSN: 1432-0533
    Keywords: Key words Alzheimer disease ; Fibrillar amyloid-β ; Astrocytes ; Microglial cell ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Ultrastructural three-dimensional reconstruction of human classical plaques in different stages of development shows that microglial cells are the major factor driving plaque formation by fibrillar amyloid-β (Aβ) deposition. The amount of fibrillar Aβ released by microglial cells and the area of direct contact between amyloid and neuron determine the extent of dystrophic changes in neuronal processes and synapses. The volume of hypertrophic astrocytic processes separating fibrillar amyloid from neuron is a measure of the protective activation of astrocytes. On the bases of the volume of amyloid star, microglial cells, dystrophic neurites, and hypertrophic astrocytic processes, and spatial relationships between plaque components, three stages in classical plaque development have been distinguished: early, mature, and late. In early plaque, the leading pathology is fibrillar Aβ deposition by microglial cells with amyloid star formation. The mature plaque is characterized by a balance between amyloid production, neuronal dystrophy, and astrocyte hypertrophy. In late classical plaque, microglial cells retract and expose neuropil on direct contact with amyloid star, enhancing both dystrophic changes in neurons and hypertrophic changes in astrocytes. In late plaques, activation of astrocytes predominates. They degrade amyloid star and peripheral amyloid wisps. The effect of these changes is classical plaque degradation to fibrillar primitive and finally to nonfibrillar, diffuse-like plaques.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010000199
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  • 26
    Electronic Resource
    Electronic Resource
    GM1-gangliosidosis in a cross-bred dog confirmed by detection of GM1-ganglioside using electrospray ionisation-tandem mass spectrometry (2000)
    Springer
    Acta neuropathologica 100 (2000), S. 409-414 
    Details
    ISSN: 1432-0533
    Keywords: Key words GM1-gangliosidosis ; Ultrastructure ; Electrospray ionisation tandem mass spectrometry ; Diagnosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The post-mortem diagnosis of lysosomal storage diseases can be confounded by the unavailability of suitable material. Here we report the diagnosis of GM1-gangliosidosis in a cross-bred dog, from which only formalin-fixed brain was available, by a combination of electron microscopy and the detection of elevated levels of GM1-ganglioside within the tissue using the novel technique of electrospray ionisation tandem mass spectrometry. Electron microscopic examination of ultrathin sections of resin-embedded tissue revealed cytoplasmic inclusions (membranous cytoplasmic and zebra bodies) in brain stem and cerebellar neurons that were characteristic of a gangliosidosis. Glycolipids were extracted from the fixed tissue and analysed by tandem mass spectrometry. Two major ions were detected, which corresponded to GM1 (d18:1–C18:0) and GM1 (d20:1–C18:0). Their identity was confirmed by comparison of their fragmentation patterns with those of authentic standards. The concentration of GM1 was approximately sixfold higher on a wet weight basis than in the brain of a normal control dog, confirming the diagnosis of GM1-gangliosidosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010000187
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  • 27
    Electronic Resource
    Electronic Resource
    Light and electron microscopic examination of endothelial cells from bovine retinal vessels in long-term cultures (2000)
    Springer
    Virchows Archiv 436 (2000), S. 249-256 
    Details
    ISSN: 1432-2307
    Keywords: Key words Endothelial cells ; Cell culture ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The aim of the present work was to examine and compare the ultrastructure of bovine retinal endothelial cells (BRECs) in vitro during several passages in a medium selective for endothelial cells. The identity of the endothelial cells was confirmed immunohistochemically, up to the tenth passage. Changes in their ultrastructure in comparison to endothelial cells in vivo occurred at the onset of culturing and not progressively with repeated passages. The cultured BRECs show high metabolic activity in all passages. While retaining their identity as endothelial cells, they modify their lipid metabolism, so that lipids are stored. This change in lipid metabolism was induced by the medium.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050038
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  • 28
    Electronic Resource
    Electronic Resource
    The ultrastructure of photoreceptor cells in the pineal organ of the blind cave salamander, Proteus anguinus (Amphibia, Urodela) (2000)
    Springer
    Pflügers Archiv 439 (2000), S. r175 
    Details
    ISSN: 1432-2013
    Keywords: Key words Pineal organ ; Photoreceptor cells ; Ultrastructure ; Proteus anguinus ; Regressive evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We studied ultrastructure of the photoreceptor cells in the pineal organ of blind, depigmented, neotenic cave salamander, Proteus anguinus. Unlike in epigean vertebrates the outer segments of most photoreceptor cells consists of concentrically arranged lamellae, however; in few cells, the outer segments contain 7-9 plasma membrane disks. In both types of photoreceptor cells the outer segments enclose lumps of vesicles of different sizes. The photoreceptor cells of Proteus anguinus are similar to those in other cavernicolous fish species.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004240000136
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  • 29
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    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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  • 30
    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.
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    URL: http://dx.doi.org/10.1023/A:1008375016038
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  • 31
    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.
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    URL: http://dx.doi.org/10.1023/A:1008391401404
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  • 32
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    Electronic Resource
    Infusional ECarboF in patients with advanced breast cancer: A very active and well-tolerated out-patient regimen (2000)
    Springer
    Annals of oncology 11 (2000), S. 1557-1561 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; carboplatinum ; chemotherapy ; continuous 5-fluorouracil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We performed a trial using the combination of epirubicin 50mg/m2/day 1, carboplatinum AUC 5/day 1 and continuous5-fluorouracil (5-FU) 200 mg/m2/day (every 4 weeks for6 months) to confirm the efficacy and low toxicity profile of thisregimen in breast cancer. In 51 patients with metastatic(n = 33) or locally advanced (n = 18)breast cancer the overall response rate was 86% (95% confidenceinterval (95% CI): 73%–94%): 94% in locallyadvanced and 81% metastatic disease. Grade 3–4 toxicity was low:4% of patients presented with febrile neutropenia, 16% withsevere palmar-plantar syndrome, 10% with Port-a-cath thrombosis. This study confirms the high efficacy of infusional 5-FU-based regimens andjustifies further research into novel promising oral 5-FU derivatives.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008378220547
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  • 33
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    Doxorubicin-based adjuvant chemotherapy in elderly breast cancer patients: The M.D. Anderson experience, with long-term follow-up (2000)
    Springer
    Annals of oncology 11 (2000), S. 1597-1601 
    Details
    ISSN: 1569-8041
    Keywords: adjuvant chemotherapy ; breast cancer ; doxorubicin ; elderly patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:The purpose of this study was to evaluate the clinicaloutcome of doxorubicin-based adjuvant chemotherapy in elderly breast cancerpatients and to compare results in elderly patients with those in youngerpatients. Patients and methods:We retrospectively reviewed the records ofall patients aged 50 years or older treated in trials of doxorubicin-basedadjuvant chemotherapy between 1974 and 1988. Old age was not an exclusioncriterion for these trials. Patient characteristics, hematologic andnonhematologic side effects, patterns of recurrence, and causes of death weredetermined for patients aged 50–64 years and for patients aged 65 yearsor older, and results were compared between these two groups.Kaplan–Meier survival curves were plotted, and tested by the generalizedWilcoxon test. Results:A total of 390 patients aged 50 years or older weretreated with doxorubicin-based adjuvant chemotherapy during the study period.Of these, 325 were aged 50–64 years (group 1), and 65 were aged 65 yearsor older (group 2). The median follow-up period for group 1 was 185 months(range 29–272+ months), and the median follow-up period for group 2 was169 months (range 128–240+ months). There were no statisticallysignificant differences between the two groups with respect to performancestatus, hormone receptor profile, tumor size, nodal status, or type oflocoregional therapy. There also were no statistically significant differencesbetween the two groups in recurrence patterns, disease-free survival, oroverall survival. The granulocyte and platelet nadirs of cycles 1, 3, and 6were similar between the two groups. No cumulative hematologic side effectswere seen in either group. The occurrence of second malignancies was extremelylow in both groups. In both groups, the majority of deaths were due toprogression of disease. Conclusions:Adjuvant doxorubicin-based chemotherapy is welltolerated in elderly breast cancer patients who have good performance statusand normal cardiac ejection fraction. Adjuvant doxorubicin-based chemotherapyin these patients results in disease-free and overall survival rates similarto those seen in younger patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008315312795
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  • 34
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    Electronic Resource
    A pilot trial assessing the efficacy of paroxetine hydrochloride (Paxil®) in controlling hot flashes in breast cancer survivors (2000)
    Springer
    Annals of oncology 11 (2000), S. 17-22 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; hot flashes ; paroxetine ; serotonin uptake inhibitors ; survivors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Many breast cancer survivors suffer debilitating hotflashes. Estrogen, the drug of choice in perimenopausal women, is generallynot recommenced to breast cancer survivors. Nonhormonal treatments are mostlydisappointing. Anecdotal reports in our institution suggested that theselective serotonin-reuptake inhibitor, paroxetine hydrochloride, might beefficacious in alleviating hot flashes. Patients and methods:Thirty women with prior breast cancer whowere suffering at least two hot flashes a day entered a single institutionpilot trial to evaluate paroxetine's efficacy in reducing the frequency andseverity of hot flashes. After completing daily diaries for one week on notherapy, the women received open-label paroxetine, 10 mg daily for one week,followed by four weeks of paroxetine, 20 mg daily. The women completedhot-flash daily diaries throughout the study period, and a health-relatedsymptom-assessment questionnaire and a quality-of-life rating scale in thefirst and sixth week of the study. Results:Twenty-seven women completed the six-week study period.The mean reduction of hot flash frequency was 67% (95%confidence interval (95% CI): 56%–79%). The meanreduction in hot flash severity score was 75% (95% CI:66%–85%). There was a statistically significantimprovement in depression, sleep, anxiety, and quality of life scores.Furthermore, 25 (83%) of the study participants chose to continueparoxetine therapy at the end of study. The most common adverse effect wassomnolence, resulting in drug discontinuation in two women, and dose reductionin two women. One woman discontinued drug due to anxiety. Conclusions:Paroxetine hydrochloride is a promising new treatmentfor hot flashes in breast cancer survivors, and warrants further evaluationin a double-blind randomized placebo-controlled trial.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008382706068
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  • 35
    Electronic Resource
    Electronic Resource
    Socio-economic deprivation and stage of disease at presentation in women with breast cancer (2000)
    Springer
    Annals of oncology 11 (2000), S. 105-107 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; socio-economic status ; stage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:This study describes and compares the pathologicalprognostic factors and surgeon assessment of stage of breast cancer of womenliving in affluent and deprived areas to assess whether clinical stage atpresentation may explain the known poorer survival outcomes for deprivedwomen. Patients and methods:A population-based review of the caserecords of 417 women with breast cancer was carried out. Results:No difference in pathological criteria was found betweenthe 88% of women living in affluent and deprived areas for whom suchdata were available. Clinical assessment of the remaining 50 cases showed thatwomen living in deprived areas were more likely to present with locallyadvanced or metastatic disease. Conclusion:The poorer survival of women from deprived areas withbreast cancer may be explained by more deprived women presenting with advancedcancers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008385321476
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  • 36
    Electronic Resource
    Electronic Resource
    Patient participation in medical decision-making: A French study in adjuvant radio-chemotherapy for early breast cancer (2000)
    Springer
    Annals of oncology 11 (2000), S. 39-45 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; choice ; decision-making process ; patient–physician relationship
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Shared decision-making is increasingly advocated asan ideal model. However, very few studies have tested the feasibility ofgiving patients the opportunity to participate in the choice of treatment. Patients and methods:Women, with non-metastatic breast cancer,eligible for non-intensified adjuvant chemotherapy attending our hospital wereproposed two administrations of chemotherapy and radiotherapy: a sequentialand a concomitant one. Two patient-questionnaires were used to elicitmotivations for their choice and their degree of comfort with the process ofdecision-making and one questionnaire to test physicians' ability to predictpatients' choice. Results:Participation rate in the study was 75.3%(n = 64). Majority (64%) of patients chose the concomitanttreatment. Multivariate analysis revealed that patients with a lower level ofeducation, who discussed the choice with social circle, and who most fearedside-effects were more likely to choose the sequential treatment. Physicianswere able to predict patients' choice in 66% of cases. 89% ofpatients declared that they were "fully satisfied" with having participatedin the choice of treatment and 79% supported shared decision-making. Conclusions:Results are in favour of promoting activeparticipation of cancer-patients in medical decision-making. The adequatedegree of such participation remains however to be elicited and tested fortherapeutic choices implying more difficult trade-offs between quantity andquality of life.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008390027720
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  • 37
    Electronic Resource
    Electronic Resource
    Second cancers after adjuvant tamoxifen therapy for breast cancer in Japan (2000)
    Springer
    Annals of oncology 11 (2000), S. 1539-1544 
    Details
    ISSN: 1569-8041
    Keywords: adjuvant therapy ; breast cancer ; second cancer ; tamoxifen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Women treated with tamoxifen for breast cancer are atincreased risk of endometrial cancer. We conducted a retrospective cohortstudy to evaluate the risk of second primary cancers after adjuvant tamoxifentherapy for breast cancer in Japan. Patients and methods:The subjects of the study were 6148 womenwho had been diagnosed with stage I, II, or IIIA unilateral primary breastcancer and had received surgical treatment during the period from January 1982through December 1990 at nine institutions in Japan. The information on eachpatient was obtained from medical records or a prospectively compiled computerdatabase at each institution. Results:Of the 6148 women, 3588 (58.4%) were administeredtamoxifen as an adjuvant treatment and 2560 (41.6%) were notadministered. Median follow-up periods were 7.64 years for tamoxifen-treatedpatients and 8.10 years for non-tamoxifen-treated patients, respectively. Theduration of tamoxifen treatment was mostly two years or less (80.7%),and few patients received tamoxifen for more than five years. The cumulativeincidence rates of all second cancers at 10 years were 4.61% and4.09% among tamoxifen-treated and non-tamoxifen-treated patients(P = 0.62), respectively, and the incidence rate ratio (IRR) forall second cancers was 1.06 (95% confidence interval (CI):0.77–1.47) after adjustment of several covariates. The numbers ofendometrial cancers was 9 and 3 among tamoxifen-treated andnon-tamoxifen-treated patients, respectively, and the IRR was 2.37 (95%CI: 0.64–8.77, P = 0.20). Of the 12 patients who developedendometrial cancer, 4 died of cancer (for 3 of them, the cause of death wasbreast cancer), and the other 8 patients were alive as of March 1996. Stomachcancer was the most frequent second cancer and the IRR was 1.34 (95%CI: 0.76–2.38, P = 0.31). There was no substantialincrease in any other type of gastrointestinal cancer such as colorectal andliver cancers among tamoxifen-treated patients. Conclusions:The incidence and risk of second primary cancersassociated with tamoxifen therapy is low. The potential benefit of adjuvanttamoxifen therapy in breast cancer patients outweighs the risk of secondprimary cancers for Japanese breast cancer patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008383804811
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  • 38
    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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  • 39
    Electronic Resource
    Electronic Resource
    p53 determination alongside classical prognostic factors in node-negative breast cancer: An evaluation at more than 10-year follow-up (2000)
    Springer
    Annals of oncology 11 (2000), S. 393-397 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; p53 ; prognostic factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:There is heterogeneity of methods and conflictingresults concerning the prognostic value of p53 in node-negativebreast cancer. The clinical value of a quantitative method for measuringtumoral p53 content still needs to be evaluated. Patients and methods: A long-term retrospective study wasconducted on 297 node-negative patients with a median follow-up greater than10 years (11 years, 101–172 months). Classic prognostic factors wereconsidered including age, tumor size, histoprognostic grade and estradiol (ER)and progesterone receptors (PR). In addition, the value of p53 determination (immunoluminometric assay in tumor cytosol) was assessed forthis long follow-up period. Results: p53 concentrations were significantly linked tothe histological grade (P = 0.001), to tumor size (P = 0.02)and ER status (P = 0.01). Higher p53 tumoral concentrationswere found in tumors with large size, pejorative histological grade andnegative ER status. In contrast, p53 tumoral concentrations were notinfluenced by menopausal or PR status. Multivariate Cox analysis demonstratesthat tumor size was the only significant predictor of disease-free survival(P = 0.049) with a risk factor at 1.38. As regards specific survival,univariate Cox analysis indicates that p53 taken as a continuousvariable is a significant predictor (P = 0.024) together withhistological grade, tumor size and ER status. In a multivariate Cox analysisthere were two significant and independent variables for predicting overallsurvival: tumor size (P = 0.031) and ER status (P = 0.015)with the highest risk factor (RR = 2.14). Conclusions:The present investigation points out that theprognostic power of p53 tumor determination evaluated at more than10 years median survival is not higher than the well-recognized classicprognostic factors in node-negative breast cancer. The present data highlightthe need to assess the prognostic value of potentially new biological factorsin node-negative breast cancer on cohorts of patients followed over periodsin excess of 10 years.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008359722254
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  • 40
    Electronic Resource
    Electronic Resource
    A comparison of methods currently used in clinical practice to estimate familial breast cancer risks (2000)
    Springer
    Annals of oncology 11 (2000), S. 451-454 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; genetic counselling ; risk assessment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:With the identification of genes predisposing tohereditary breast cancer, the accurate and consistent estimation of a woman'srisk of developing breast cancer based on her family history is of paramountimportance if national service guidelines are to be developed. Patients and methods:The residual lifetime risk of developingbreast cancer was estimated for 200 women attending a breast cancer geneticassessment clinic by three different methods currently in use in the UK. Riskswere computed on the basis of the Cancer and Steroid Hormone (CASH) study dataand were classified as ‘low/moderate’ (〈20%) or ‘high’(〉20%). These risk categories are representative of those currentlyused to allocate surveillance and genetic testing. Risks were then comparedto estimates derived by other methods used in current clinical practice,including those of Houlston and Murday. Results:The CASH data-based method ascribed 27% to thehigh risk category, as compared to 53% for the combined Houlston andMurday methods. A method based on the number of affected relatives aloneascribed only 14% to the high risk category. Overall, 108 (54%)women were placed in the same risk category by all three methods. Conclusions:This study demonstrates that there is a significantdegree of variability between methods currently used to estimate breast cancerrisk which has serious implications for individual patient management, serviceprovision and multicentre studies evaluating the benefits of genetic testingfor breast cancer susceptibility.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008396129543
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  • 41
    Electronic Resource
    Electronic Resource
    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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  • 42
    Electronic Resource
    Electronic Resource
    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.
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    URL: http://dx.doi.org/10.1023/A:1008396330433
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  • 43
    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.
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    URL: http://dx.doi.org/10.1023/A:1008333327500
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  • 44
    Electronic Resource
    Electronic Resource
    Adjuvant chemotherapy in node negative breast cancer: Patterns of use and oncologists' preferences (2000)
    Springer
    Annals of oncology 11 (2000), S. 631-633 
    Details
    ISSN: 1569-8041
    Keywords: adjuvant chemotherapy ; attitudes ; breast cancer ; consensus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:A worldwide variation in policy is seen regardingadjuvant systemic treatment for node negative breast cancer (NNBC). After thefirst presentations of the 10-year EBCTCG results, a study was carried out inthe Netherlands to assess patterns of care and to obtain the views ofoncologists as to what constitutes a worthwhile benefit from treatment. Methods:A questionnaire regarding patterns of use of andpreferences for adjuvant chemotherapy in younger women was mailed to surgical,medical and radiation oncologists in the Netherlands. Results:Thirty-five percent stated that NNBC patients under 50in their hospital never received adjuvant chemotherapy. The majorityconsidered a 10-year survival gain of 6%–10% sufficientto warrant the use of chemotherapy in patients under 50. Surgical oncologistsrequired a larger benefit from treatment than radiotherapists and medicaloncologists. The more frequently oncologists treated patients in a researchcontext, the less benefit they required from treatment to make it worthwhile. Conclusions:Data such as these are valuable input into theprocess of guideline development, and may help discussion within theprofession as to what benefit offsets the burden of treatment.
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    URL: http://dx.doi.org/10.1023/A:1008379628579
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  • 45
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    Electronic Resource
    Phase II study of docetaxel in patients with liver metastases from breast cancer (2000)
    Springer
    Annals of oncology 11 (2000), S. 541-546 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; clinical trial ; docetaxel ; hepatic metastases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Previous phase II studies of docetaxel have indicatedthat hepatic metastases from breast cancer respond well to first-linetreatment with docetaxel. The objective of this prospective, open label phaseII study therefore was specifically to evaluate the activity and safety ofdocetaxel in this indication. Patients and methods:The study recruited 47 women (mean age 50years, range 33–66 years) with hepatic metastases from breast cancer whofulfilled the eligibility criteria. After premedication with steroids,patients received a one-hour intravenous infusion of docetaxel 100mg/m2 at three-weekly intervals for up to eight cycles. Responseto treatment during medication was assessed after three, six and whereappropriate, eight cycles and every three month follow-up thereafter, untildisease progression or death. Results:The best overall response rate (ORR) for evaluablepatients was 64.3% (95% CI: 48.0%–78.5%).In terms of the primary efficacy parameters, the ORR at the sixth cycle oftreatment was 62% (95% CI: 45%–80%) with17% complete responses. The median duration of response was 139 days(95% CI: 111–216 days) and the median survival durationcalculated on an intent-to-treat basis was 335 days (227–568 days,95% CI). One (2%) toxic death was reported. Conclusions:Docetaxel is a highly effective cytotoxic agent inthe treatment of patients with liver metastases from breast cancer.
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    URL: http://dx.doi.org/10.1023/A:1008383707159
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  • 46
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    Electronic Resource
    Sentinel node biopsy as a practical alternative to axillary lymph node dissection in breast cancer patients: An approach to its validity (2000)
    Springer
    Annals of oncology 11 (2000), S. 701-705 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; lymph nodes ; sentinel lymph node biopsy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Sentinel node biopsy (SNB) has been proposed as analternative to axillary lymph-node dissection (ALND) in breast cancer. Beforeimplementing SNB in our practice, we wished to test its validity by comparingit to the standard ALND, both in our hands and with other reported series. Patients and methods:One hundred thirty-two patients wereincluded prospectively. SNB and immediate ALND were performed. For SNB, atechnetium-colloid was used to produce preoperative lymphoscintigraphy andintraoperative gamma-probe search for the SN. Serial sectioning andimmunostains were used on the SN. A comprehensive review of the literature wasdone in order to run a meta-analysis of diagnostic tests using a summaryreceiver operating characteristic curve (SROC) to calculate the pooledparameters of sensitivity and associated 95% confidence interval(95% CI), including our own data. Results:Our technical success rate was 96%. Localsensitivity was 96%, with a 95% CI from85%–99%. Seven patients were upstaged by the SNB. Aliterature search identified 18 studies published from 1996–1999.Estimates of sensitivity ranged from 83%–100%. The pooleddata meta-analysis gave a global sensitivity of 91%, with a 95%CI from 89%–93%. The area under the global SROC curve was0.9967. Conclusions:The minimally invasive SNB was shown to be apractical alternative to ALND. We propose to use local as well as globalsensitivity and associated 95% CI to test the validity of SNB in theclinical setting. Due to limitations of ALND as the golden standard, SNB canin fact be considered a more accurate method for nodal staging.
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    URL: http://dx.doi.org/10.1023/A:1008377910967
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  • 47
    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.
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    URL: http://dx.doi.org/10.1023/A:1008346708604
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  • 48
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    Electronic Resource
    Response to primary chemotherapy in breast cancer patients with tumors not expressing estrogen and progesterone receptors (2000)
    Springer
    Annals of oncology 11 (2000), S. 1057-1059 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; estrogen receptor ; progesterone receptor ; preoperative chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:We recently demonstrated that in premenopausalpatients with estrogen receptors (ER)-absent tumors, early initiation ofsystemic chemotherapy after primary surgery might improve outcome. These dataindicate a different responsiveness to chemotherapy for tumors not expressinghormone receptors. To test this hypothesis we evaluated the responsiveness topreoperative chemotherapy in patients with ER and progesterone receptors(PgR)-absent tumors. Patients and methods:Patients with biopsy-provenT2–T3, N0–2 breast cancertreated at a single institution from January 1995 to August 1999 withpreoperative chemotherapy were retrospectively evaluated. ER and PgR weredetermined immunohistochemically and classified for this purpose as absent(0% of the cells positive) or positive (≥1% of the cells). Results:On 117 evaluable patients 72 had an objective response(61%). A significant difference in response was observed for patientswith ER and PgR absent compared with those with ER and/or PgR-positive tumors(82% vs. 57%,P = 0.03 Fishers's exact test).Pathological complete remission rates were also significantly different in thetwo groups (23% vs. 7%, respectively; P = 0.04). Conclusions:The different degree of response according to hormonereceptors expression supports the hypothesis that tumors not expressing bothER and PgR might represent a different clinical entity in terms ofchemotherapy responsiveness.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008334404825
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  • 49
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    Electronic Resource
    Atypical morphological characteristics and surface antigen expression of Burkholderia pseudomallei in naturally infected human synovial tissues (2000)
    Springer
    Modern rheumatology 10 (2000), S. 129-136 
    Details
    ISSN: 1439-7609
    Keywords: Key words Septic arthritis ; Surface antigens ; Ultrastructure ; Burkholderia pseudomallei ; IEM
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Burkholderia pseudomallei is the causative agent of melioidosis, a disease that frequently runs a protracted course and is very difficult to eradicate. The mechanisms that this organism uses to escape from host defense mechanisms and antibiotics are not well understood. The aim of the study was to compare the morphological characteristics and surface antigen expression of B. pseudomallei in naturally infected human synovial tissues with the characteristics of bacteria grown in culture media. Immunoelectron microscopic study was performed in four synovial biopsies taken from four B. pseudomallei septic arthritis patients. Colonies of pathogenic B. pseudomallei collected from culture media were used as positive controls. Polyclonal antibody to whole cell B. pseudomallei was used as a primary antibody. Complete bacteria-like particles were demonstrated both extracellularly and intracellularly in all four synovial specimens. The intracytoplasmic location of B. pseudomallei and mononuclear phagosome containing microcolony-like structures were demonstrated. B. pseudomallei found in the synovial membrane samples were mostly atypical, with fewer cytoplasmic electron lucent granules. Immunogold staining of bacterial surface antigens was weaker than staining of positive controls. We demonstrated atypical forms of B. pseudomallei and evidence for suppression of its surface antigens in naturally infected human synovial tissues. This adaptation may help bacteria to survive despite host immune surveillance and treatment with antibiotics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s101650070019
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  • 50
    Electronic Resource
    Electronic Resource
    Glomus claroideum forms an arbuscular mycorrhiza-like symbiosis with the hornwort Anthoceros punctatus (2000)
    Springer
    Mycorrhiza 10 (2000), S. 15-21 
    Details
    ISSN: 1432-1890
    Keywords: Anthoceros punctatus ; Arbuscular mycorrhiza ; Bryophytes ; Glomus ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Glomus claroideum (Schenck & Smith emend. Walker & Vestberg) were investigated for ability to form arbuscular mycorrhiza-like symbioses with the hornwort Anthoceros punctatus (L.). Spores were transferred to a cellulose acetate filter on water agar and a small portion of an Anthoceros thallus was placed directly upon the spores. Light-microscope observations 20 days after inoculation revealed branched hyphae growing within the thallus. After 45 days, arbuscules and vesicles were studied by light- and electron-microscopy. After 60 days in water agar culture, the colonised Anthoceros thalli were transferred to a low-nutrient medium agar. Hyphae spread in the agar and newly formed spores were observed 5 weeks after the transfer. After 4 months, about 1000 spores were formed in each Petri dish. This is the first report of an experimentally established arbuscular mycorrhiza-like symbiosis between an identified fungus belonging to the Glomales and a bryophyte.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s005720050282
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  • 51
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    Electronic Resource
    Chronic effects of streptozotocin-induced diabetes on the ultrastructure of rat ventricular and papillary muscle (2000)
    Springer
    Acta diabetologica 37 (2000), S. 119-124 
    Details
    ISSN: 1432-5233
    Keywords: Key words Streptozotocin ; Diabetes ; Ventricular myocyte ; Cardiac muscle ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Contractile dysfunctions have been demonstrated in different experimental models of diabetes which have similar characteristics to many of the abnormalities found in the clinical setting. Administration of streptozotocin (STZ) to young adult rats induces β-cell necrosis of the pancreas which gives rise to hypoinsulinaemia and hyperglycaemia, features which are also seen in untreated type 1 clinical diabetes. We have investigated the chronic effects of STZ-induced diabetes on contraction in rat ventricular myocytes and ultrastructure of cardiac muscle. Diabetes was induced in male Wistar rats (230–270 g) with a single injection of STZ (60 mg kg−1). At 2 and 10 months after STZ treatment, the amplitude of contraction was larger in diabetic compared to control myocytes. Time to peak contraction was significantly longer at 2 months but appeared to normalise at 10 months after STZ treatment. In contrast, time to half relaxation of contraction was not significantly different after 2 months but was significantly reduced at 10 months after STZ treatment compared to control. Transmission electron microscope examination of cardiac muscle showed that the ultrastructure of cardiac muscle, especially structures associated with contraction, were not greatly altered after STZ treatment. Sarcomere lengths were not significantly different in papillary or ventricular muscle at 4 or 8 months after STZ treatment compared to control. Our data provide evidence that morphological defects in contractile myofilaments and associated structures cannot explain contractile dysfunctions seen in ventricular myocytes from STZ-treated animals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s005920070013
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  • 52
    Electronic Resource
    Electronic Resource
    Effect of osmotic stress on tolerance of air-drying and cryopreservation ofArabidopsis thaliana suspension cells (2000)
    Springer
    Protoplasma 214 (2000), S. 227-243 
    Details
    ISSN: 1615-6102
    Keywords: Arabidopsis thaliana ; Cryopreservation ; Dehydration ; Thermal analysis ; Sucrose ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Arabidopsis thaliana suspension cells were preserved in liquid nitrogen for over three years, using embedding of cells in calcium-alginate prior to subculture in sucrose-enriched medium, air-drying, and direct quenching in liquid nitrogen. Survival of cells reached 34%, yielding regrowth at the surface of all cryopreserved beads in less than 7 days. Following pretreatment and dehydration, the water content dropped from 2300% to 34% with respect to dry weight. Differential scanning calorimetry showed that glass transition occurred on cooling, followed by a slight crystallization event on rewarming. The survival of cells was independent of the cooling rate. The tolerance of the acute dehydration step increased progressively with sucrose pretreatment duration, indicating the requirement for adaptative cellular alterations. Ultrastructural studies revealed several changes in cells after sucrose pretreatment prolonged from 1 to 7 days: reversal of the initially plasmolyzed state, microvacuolation, numerous autophagic structures, scarcity of ribosomes, increase in number and size of starch grains. No cell division seemed to occur during this period. After air-drying and after a freeze-thaw cycle, followed by 24 h rehydration, regenerating cells had recovered a high level of ultrastructural organization and contained numerous polysomes suggesting an intense metabolic activity. Trehalose, a cryoprotective disaccharide not considered to be a metabolic substrate, yielded only 70% regrowth after freezing. Biochemical analysis showed that soluble sugars accumulated during the pretreatment, essentially sucrose or trehalose; the monosaccharide content also increased. In the light of these results, the action of sucrose in inducing freezing tolerance is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01279067
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  • 53
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    Electronic Resource
    Ultrastructure and anatomy of nematode-induced syncytia in roots of susceptible and resistant sugar beet (2000)
    Springer
    Protoplasma 211 (2000), S. 39-50 
    Details
    ISSN: 1615-6102
    Keywords: Beta vulgaris ; Cyst nematodes ; Histology ; Resistance mechanism ; Syncytium ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Using susceptible and resistant sugar beet lines, comparative analyses of root histology and ultrastructure were made during invasion by nematodes and the induction and formation of specific feeding structures (syncytia).The resistant line carried the resistance geneHs1pro−1.Nematodes were able to invade and induce functional syncytia in roots of resistant and susceptible lines. However, syncytia in resistant roots were smaller and less hypertrophied. The vacuolar system of syncytia in susceptible plants contained many small vacuoles. In resistant plants vacuoles were larger but less numerous. Smooth endoplasmic reticulum prevailed in syncytial protoplasts of susceptible plants, whereas almost only rough endoplasmic reticulum occurred in syncytia in resistant plants. The most conspicuous and hitherto undescribed trait of syncytia in resistant roots was the initial appearance of loose, and later compact, aggregations of the endomembrane system which composed most of the endoplasmicreticulum system of syncytia at later stages. Syncytia in resistant plants usually degraded before the nematodes reached their adult stage. The appearance of membrane aggregations and the other resistance-specific features are discussed in relation to their possible effects on syncytium function and role in nematode resistance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01279898
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  • 54
    Electronic Resource
    Electronic Resource
    Structural changes during early embryogenesis in wheat pollen (2000)
    Springer
    Protoplasma 211 (2000), S. 94-102 
    Details
    ISSN: 1615-6102
    Keywords: Androgenesis ; Embryogenesis ; Microspore culture ; Pollen ; Ultrastructure ; Wheat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary We have made a detailed cytological examination of the development of wheat embryoids, monitoring their initial divisions from two to ten cells by both light and electron microscopy. According to our observations the first embryogenic division is symmetrical. After the androgenesis induction treatment, there is a decrease in ribosome population with cells that have inactive nucleoli made up almost exclusively of a dense fibrillar component. This population is restored after initial embryogenic divisions. During the initial divisions the embryogenic pollen grains do not appear to change in size and the pollen wall remains intact. The exine undergoes no modification but the intine thickens, and we have observed that the thickness of the intine can be used as a cytological marker of androgenesis. The walls separating the cells obtained after embryogenic division contained numerous plasmodesmata. The beginnings of embryo polarization and cell differentiation could be made out in the very early pollen embryoids.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01279902
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  • 55
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    Electronic Resource
    Expression of bone sialoprotein and osteopontin in breast cancer bone metastases (2000)
    Springer
    Clinical & experimental metastasis 18 (2000), S. 253-260 
    Details
    ISSN: 1573-7276
    Keywords: bone sialoprotein ; osteopontin ; breast cancer ; metastasis ; bone metastases ; immunohistochemistry ; in situ hybridization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Bone sialoprotein (BSP) and osteopontin (OPN) are prominent, mineral-associated proteins in the extracellular matrix of bone that have been implicated in the metastatic activity of cancer cells. The expression of BSP, which is normally restricted to mineralizing tissues, has been observed in cancers with a high propensity for forming bone metastases. To investigate the relationship between BSP expression and the formation of bone metastases we have conducted an initial study of the expression of BSP in 10 intraductal breast carcinoma bone metastases using immunostaining and in situ hybridization, and compared the expression with OPN. The metastases were characterized by the infiltration of tumour cells into bone with extensive bone resorption evident. Moderate to strong staining for BSP was observed in all (100%) carcinomas, which also expressed BSP mRNA as determined by in situ hybridization. Variable staining for BSP was also observed in the mineralized bone and expression of BSP mRNA could be observed in osteoblastic cells on the bone surface and in some osteocytes at sites of bone remodelling. Contrary to a previous report, BSP expression could be demonstrated by PCR in three breast cancer cell lines, MCF-7, T47-D and MDA-MB-231. Moreover, in sub-cutaneous tumours formed by MDA-MB-231 breast cancer cells injected into athymic mice, higher immunostaining for BSP was seen in large ulcerating tumours in which mineral deposits were formed. In contrast to BSP, staining for OPN in bone metastases was generally restricted to the interface between tumor cells and bone surface of the carcinomas. While OPN staining was also observed in the cytoplasm of osteoclasts, which showed strong hybridization to a digoxygenin-labelled OPN cRNA probe, expression of OPN was not clearly detectable in the tumour cells. These studies provide the first demonstration of BSP expression by tumour cells in bone metastases and support the concept that BSP may have a role in targeting metastatic cells to bone. Expression of OPN in bone metastases appears to be related to increased bone resorptive activity by osteoclasts.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006754605901
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  • 56
    Electronic Resource
    Electronic Resource
    Keratinocyte growth factor-induced motility of breast cancer cells (2000)
    Springer
    Clinical & experimental metastasis 18 (2000), S. 573-580 
    Details
    ISSN: 1573-7276
    Keywords: breast cancer ; cell motility ; KGF ; metastasis ; MCF-7 ; T-47D ; ZR-75-1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Endogenous growth factors and cytokines are known to have a major influence on the progression, motility and invasiveness of tumor cells. We have reported previously that conditioned media from mouse fibroblasts increases the motility of breast cancer cells. Further, we determined that keratinocyte growth factor (KGF) was an active factor from mouse fibroblasts responsible for most of the motility response in breast cancer cells. The present study examined the effect of human KGF on the motility of estrogen receptor (ER)-positive and ER-negative human breast cancer cell lines in culture using time-lapse videomicroscopy to quantify cell motility. In the present study we observed that recombinant human KGF enhanced several parameters of cellular motility in ER-positive cells but not in ER-negative cell lines. Further, we observed that the level of KGF receptor (KGFR) expression in ER-positive cells was much greater than in the ER-negative cell lines. The motility response to KGF was found to be both dose-and time-dependent. Of the three ER-positive breast cancer cell lines tested, MCF-7 cells were the most responsive to KGF stimulation. Finally, MCF-7 cells grown in estrogen-depleted media did not respond to KGF. These results suggest that KGF from stromal tissue surrounding a primary tumor mass can enhance tumor cell motility and may be an early signal in the progression of breast cancer cells to a more motile and metastatic phenotype. Thus, KGF, KGFR and/or the KGF signaling pathway may be important therapeutic targets for the treatment or prevention of breast cancer metastasis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1011997317994
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  • 57
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    Electronic Resource
    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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  • 58
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    Electronic Resource
    Chemotherapy-induced Complete Regression of Choroidal Metastases and Subsequent Isolated Leptomeningeal Carcinomatosis in Advanced Breast Cancer: A Case Report and Literature Review (2000)
    Springer
    Journal of neuro-oncology 47 (2000), S. 161-165 
    Details
    ISSN: 1573-7373
    Keywords: choroidal metastasis ; leptomeningeal carcinomatosis ; breast cancer ; docetaxel ; mitoxantrone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Choroidal metastases from breast cancer represent an unusual metastatic presentation that has been traditionally treated with radiation therapy. Herein, we report a case of metastatic breast cancer presenting with pulmonary, cutaneous, lymph node and symptomatic choroidal metastases treated with systemic combination chemotherapy incorporating docetaxel and mitoxantrone without induction or consolidation radiation therapy to control visual symptoms from choroidal metastases. The patient experienced a durable complete remission in all metastatic sites that was maintained for 21 months since the initiation of chemotherapy, afterwhich she developed isolated leptomeningeal carcinomatosis managed successfully with intensive intrathecal methotrexate and whole brain irradiation leading to a new complete remission maintained until this report; 11 months after its presentation. This is the first case to our knowledge reporting complete regression of choroidal metastases with docetaxel-based chemotherapy as the only treatment modality and subsequent isolated leptomeningeal carcinomatosis recurrence.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006449215047
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  • 59
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    Electronic Resource
    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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  • 60
    Electronic Resource
    Electronic Resource
    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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  • 61
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    Electronic Resource
    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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  • 62
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    Electronic Resource
    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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  • 63
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    Electronic Resource
    Effects of glutathione on thiol redox systems, chromosomal aberrations, and the ultrastructure of meristematic root cells ofPicea abies (L.) Karst. (2000)
    Springer
    Protoplasma 212 (2000), S. 227-235 
    Details
    ISSN: 1615-6102
    Keywords: Glutathione ; Root ; Chromosomal aberration ; Ultrastructure ; Picea abies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Young spruce seedlings (Picea abies [L.] Karst.) grown in hydroponic culture were exposed to three different concentrations (50,100, and 500 μM) of reduced glutathione for 24 h. These physiologically relevant concentrations of glutathione had a multiple effect on the investigated tissue. Feeding of glutathione to roots increased the concentrations of thiols (glutathione, cysteine, and γ-glutamyl-cysteine) in roots, decreased the rate of cell divisions, induced mitotic abnormalities, and affected the cell ultrastructure. Electron micrographs showed effects such as advanced vacuolation, dilated rough-endoplasmic-reticulum cisternae, and separations of the plasma membrane from the cell wall.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01282923
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  • 64
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    Electronic Resource
    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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  • 65
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    Electronic Resource
    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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  • 66
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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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  • 67
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    Electronic Resource
    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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  • 68
    Electronic Resource
    Electronic Resource
    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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  • 69
    Electronic Resource
    Electronic Resource
    Leptin and insulin growth factor I in relation to breast cancer (Greece) (2000)
    Springer
    Cancer causes & control 11 (2000), S. 383-388 
    Details
    ISSN: 1573-7225
    Keywords: breast cancer ; insulin growth factor I ; leptin ; postmenopause ; premenopause
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objectives: Because both breast cancer and the hormone leptin are associated with obesity and reproductive phenomena in women, we have examined whether there is a relationship between leptin and breast cancer among premenopausal and postmenopausal women. We have also evaluated in this dataset the association of IGF-I with breast cancer. Methods: Seventy-five cases, diagnosed during mammographic screening, with incident breast cancer were matched for age and type of permanent residence with seventy-five controls from those screened negative in the same study base. Results: There was no evidence for an association between IGF-I and either premenopausal or postmenopausal breast cancer risk or between leptin and postmenopausal breast cancer. Among premenopausal women, however, there was a strong and statistically significant inverse association of leptin with breast cancer. Conclusion: We did not confirm the positive association, reported from other investigations, of IGF-I with premenopausal breast cancer risk. We have found evidence, however, that leptin may be inversely related to breast cancer risk among premenopausal women. The latter finding is not biologically implausible and deserves to be examined in additional datasets.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008903727238
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  • 70
    Electronic Resource
    Electronic Resource
    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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  • 71
    Electronic Resource
    Electronic Resource
    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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  • 72
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    Electronic Resource
    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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  • 73
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    Electronic Resource
    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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  • 74
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    Electronic Resource
    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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  • 75
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    Electronic Resource
    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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  • 76
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    Electronic Resource
    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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  • 77
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    Electronic Resource
    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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  • 78
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    Electronic Resource
    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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  • 79
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    Electronic Resource
    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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  • 80
    Electronic Resource
    Electronic Resource
    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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  • 81
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    Electronic Resource
    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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  • 82
    Electronic Resource
    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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  • 83
    Electronic Resource
    Electronic Resource
    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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  • 84
    Electronic Resource
    Electronic Resource
    Loss of Heterozygosity in Bilateral Breast Cancer (2000)
    Springer
    Breast cancer research and treatment 64 (2000), S. 241-251 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; bilateral ; loss of heterozygosity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Women who develop bilateral breast cancer at an early age are likely to harbour germline mutations in breast cancer susceptibility genes. The aim of this study was to test for concordant genetic changes in left and right breast cancer of young women (age 〈50) with bilateral breast cancer that may suggest an inherited breast cancer predisposition. Microsatellite markers were used to test for loss of heterozygosity (LOH) in left and right tumours for 31 women with premenopausal bilateral breast cancer. Markers adjacent to or within candidate genes on 17p (p53), 17q (BRCA1), 13q (BRCA2), 11q (Ataxia Telangiectasia-ATM) and 3p (FHIT) were chosen. Mutational testing for BRCA1 and BRCA2 was performed for cases where blood was available. Concordant LOH in both left and right tumours was demonstrated for at least one of the markers tested in 16/31(54%) cases. Where allelic loss was demonstrated for both left and right breast cancer, the same allele was lost on each occasion. This may suggest a common mutational event. Four cases showed concordant loss of alleles in both left and right breast cancer at D17S791 (BRCA1). BRCA1 mutations were identified in two of these cases where blood was available. Four cases showed concordant LOH at D13S155 (BRCA2). Concordant LOH was further demonstrated in seven cases for D11S1778 (ATM) and four cases for D3S1300 (which maps to the FHIT gene), suggesting a possible role for these tumour suppressor genes in this subgroup of breast cancer patients. No concordant allelic loss was demonstrated for D17S786 suggesting that germline mutations in p53 are unlikely in such cases of bilateral breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026575619155
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  • 85
    Electronic Resource
    Electronic Resource
    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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  • 86
    Electronic Resource
    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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  • 87
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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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  • 88
    Electronic Resource
    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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  • 89
    Electronic Resource
    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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  • 90
    Electronic Resource
    Electronic Resource
    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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  • 91
    Electronic Resource
    Electronic Resource
    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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  • 92
    Electronic Resource
    Electronic Resource
    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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  • 93
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    Electronic Resource
    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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  • 94
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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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  • 95
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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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  • 96
    Electronic Resource
    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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  • 97
    Electronic Resource
    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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  • 98
    Electronic Resource
    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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  • 99
    Electronic Resource
    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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  • 100
    Electronic Resource
    Electronic Resource
    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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