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  • 2000-2004
  • 1995-1999  (763)
  • 1970-1974
  • 1960-1964
  • 1890-1899
  • 1997  (763)
  • Inorganic Chemistry  (608)
  • Computational Chemistry and Molecular Modeling
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  • breast cancer
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Years
  • 2000-2004
  • 1995-1999  (763)
  • 1970-1974
  • 1960-1964
  • 1890-1899
Year
  • 1
    ISSN: 1436-2813
    Keywords: breast cancer ; prognostic factor ; young age ; survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of age on the prognosis of breast cancer remains controversial. To investigate the role of age, we reviewed 316 patients with stage I or 1I breast cancer. There were 14 patients below 34, 146 between 35 and 49, 115 between 50 and 65, and 41 over 66 years of age. No correlations were observed between age and clinicopathological variables. Breast cancer patients aged 34 or less had a significantly worse survival compared to those in the older age groups. Multivariate analysis also showed younger age to be a significant factor, followed by lymph node status. Therefore, younger age at onset is considered to be an independent prognostic factor.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1436-2813
    Keywords: breast cancer ; radiosensitivity ; bax ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Bax-a, a splice variant ofbax which promotes apoptosis, is expressed in many kinds of untransformed cell lines and breast tissue, whereas only weak or no expression could be detected in breast cancer cell lines and malignant breast tissue. Human breast cancer MCF-7 cells, which have a weakbax gene expression, were stably transfected with pCX2neobax encoding humanbax and neomycin-resistant genes, and two unique clones (MCF-7/bax-1 and MCF-7/bax-2) were thus generated which expressed different levels ofbax-α. Sensitivity to ionizing radiation (IR) was examined and each was more sensitive to IR than the parental MCF-7 cells. The degree of enhancement in radiosensitivity was dependent on the expression level ofbax, and IR was found to induce intranucleosomal DNA fragmentation in stable transfectant but not in parent cells, thus suggesting that this sensitization is due to apoptosis. We suggest that exogenousbax-α expression might therefore be one of the factors determining cellular radiosensitivity in MCF-7 breast cancer cells and may potentially have a therapeutic application by enhancing radiation sensitivity in breast cancer cells.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1436-2813
    Keywords: breast cancer ; lymph node metastasis ; survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To investigate the impact of the number of involved lymph nodes on survival, we retrospectively reviewed the data for 37 patients with breast cancer and metastases of ten or more lymph nodes who underwent treatment between 1987 and 1995. Based on the number of positive lymph nodes, the patients were allocated to one of three groups. The 5-year disease-free and overall survival rates for all patients were both 53.0%. The 7 patients with 26 or more positive nodes had significantly poorer survival than either the 19 patients with 10–15 nodes, or the 11 with 16–25 nodes, although there were no differences in survival related to the extent of node involvement as defined using the Japanese staging system. Patients with 50%–75% frequency of metastasis, defined as the positive nodes/total resected nodes, had significantly better survival than those with 〈50% or 〉75% frequency. These results indicate that the number of involved lymph nodes is related to survival and that 25 positive nodes is a cutoff point in breast cancer patients with ten or more positive lymph nodes.
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  • 4
    ISSN: 1436-2813
    Keywords: breast cancer ; breast conserving surgery ; surgical margin ; frozen section ; local recurrence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study was conducted to analyze retrospectively the results of performing sector resection on 56 breasts in 54 patients with breast cancer. The glands were resected with a 2-cm tumor-free margin on both lateral sides and the distal side, and with more than a 3-cm tumor-free margin on the nipple side. The frequency of positive resection margins for the cancer cells was 7/56 (12.5%) on the nipple side and 12/46 (26.1%) on the lateral sides, with an overall frequency of 15/56 (26.8%). There were positive resected margins for cancer cells on both the nipple and lateral sides in 4/46 patients (9%) Assuming the equivocal margins were positive for cancer cells, an accurate diagnosis by frozen section examination was made in 51 of the 56 operations (91.1%). Additional resection of the margins was performed in all 20 cases of a positive resected margin for cancer cells according to the diagnosis by frozen section. Thereafter, the resected margins became negative in 13 cases (65%), but remained positive in 7 cases (35%). These results show that performing diagnosis by frozen section of the surgical margins is an effective guide to resecting tumors adequately.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Annals of oncology 8 (1997), S. 3-6 
    ISSN: 1569-8041
    Keywords: adjuvant therapy ; breast cancer ; high-dose chemotherapy ; metastases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Breast cancer is the most common female cancer – one woman in 12 will have breast cancer at some stage during her life. Early-stage breast cancer is often curable; however, the prognosis is much worse in patients with multiple lymph node involvement or metastatic disease. The overall survival at five years is approximately 60% in women with positive lymph nodes, decreasing to 27%–44% when more than 10 lymph nodes are involved. After metastatic relapse, the mainstay of treatment is palliative. However, recent advances in supportive care have facilitated investigation into the use of dose-intensive chemotherapy regimens. The advancement of high-dose chemotherapy in breast cancer and results from clinical trials in both metastatic disease and the adjuvant setting are reviewed here. The true benefit of high-dose chemotherapy in breast cancer continues to be investigated. It is hoped that the results of worldwide, randomised clinical trials, due within the next three to five years, will provide a clearer indication of the value of high-dose chemotherapy, its costs and the patients whom it will benefit most.
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  • 6
    ISSN: 1569-8041
    Keywords: breast cancer ; high-dose chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: In a previous study we applied doxorubicin and cyclophosphamide in a dose-intensive regimen with GM-CSF to patients with metastatic breast cancer (MBC). That treatment failed to prolong the remission duration compared to conventional-dose chemotherapy. In the present study we escalated the dosages of the same agents to: 1) determine the maximum tolerated dosages (MTD) when given for three cycles with G-CSF mobilised peripheral blood progenitor cell (PBPC) reinfusion and 2) evaluate the antitumour effect of this regimen. Patients and methods: For mobilisation of PBPC, G-CSF 15 µg/kg/day was given subcutaneously (s.c.), and in subsequent cohorts leucapheresis was started on days 3, 4 or 6. The intention was to treat MBC patients with three cycles of doxorubicin and cyclophosphamide at a starting dose of doxorubicin 90 mg/m2 and cyclophosphamide 1000 mg/m2. Dosages were then escalated in subsequent cohorts of at least three patients. In case of dose-limiting mucositis, only the dose of cyclophosphamide was escalated in the next cohort. Results: Twenty-one patients entered this protocol, of which 18 patients received high-dose chemotherapy. The mobilisation of PBPC using G-CSF only was sufficient for three cycles of high-dose chemotherapy in 10 of 21 (47%) patients. Mucositis precluded dose escalation of doxorubicin beyond 110 mg/m2. The MTD in this combination was 110 mg/m2 for doxorubicin, and 4 g/m2 for cyclophosphamide, with haemorrhagic cystitis being the dose-limiting toxicity. The overall response rate was 78% (95% confidence interval (95% CI): 57%–97%), with 22% (95% CI: 3%–41%) complete responses. Conclusion: The MTD of this three cycle high-dose regimen was doxorubicin 110 mg/m2 and cyclophosphamide 4 g/m2 with mucositis and cystitis being dose-limiting toxicities. Although the primary aim was not the evaluation of antitumour effect, this high-dose regimen does not appear to provide an improvement of treatment results in comparison with our previous study with the same drugs at moderately high-dosages without stem cell support.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Annals of oncology 8 (1997), S. 939-943 
    ISSN: 1569-8041
    Keywords: breast cancer ; Taxol–anthracycline combination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Annals of oncology 8 (1997), S. 149-153 
    ISSN: 1569-8041
    Keywords: breast cancer ; quality of sex life ; sexual dysfunction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: This study examined the impact of breast cancer therapyon women's sexuality. Patients and methods: A questionnaire concerning various sexualproblems experienced before and after treatment was anonymously completed by50 women in the outpatient clinic of our hospital's Division of RadiationOncology. To be eligible, subjects had to be disease-free and sexually active.They also had to have undergone surgery at least one year previously and havecompleted CT and/or RT. Fifty-eight percent of the women involved hadundergone mastectomy and 42% had undergone quadrantectomy followed byRT. Results: Ninety percent of the subjects continued sexual activityafter treatment, but there was an increase in the incidence of sexual problemswhich resulted in a slight reduction in the quality of their sex lives.Sixty-four percent of the women experienced an absence of sexual desire and48% low sexual desire, while 38% had dyspareunia, 44%frigidity and 42% lubrication problems. Vaginismus, brief intercourseand female orgasmic disorder were reported by 30% of the subjects.Thirty-six percent suffered from sexual dysfunction before treatment, whichworsened in about 27%, while in 49% of women sexual problemsarose mainly after chemotherapy (26%) or surgery (12%). Aboutone-half experienced changes in the relationship with their partner. Conclusion: Breast cancer patients experienced sexual dysfunction;ours found it easier to discuss the problems with their partner during theirillness (62%) than with doctors and psychologists (15%).
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1569-8041
    Keywords: ATase ; breast cancer ; drug resistance ; PGP ; GPx ; GSH ; GST ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The identification of new factors predicting relapse,outcome and response to systemic therapy in breast cancer is warranted. Themeasurement of biological markers such as drug resistance parameters (DRPs),which are part of the phenotype of malignant cells and contribute toresistance to anti-cancer drugs may be a possibility, which may ultimatelylead to improvement of therapeutic results. Patients and methods: The level of glutathione (GSH), activities ofglutathione-S-transferase (GST), glutathione-peroxidase (GPx),06-alkylguanine-DNA-alkyltransferase (ATase), and P-glycoprotein (PGP) weremeasured in tumor and adjacent tumor free tissue samples from 89 consecutive,untreated females with breast cancer and correlated with clinical andprognostic factors. Early breast cancer (EBC) was diagnosed in 56 patients,22 patients had locally advanced (LABC) and 11 patients metastatic breastcancer. Results: All DRPs showed significantly higher expression in tumorthan in tumor free tissues. GPx was positively correlated with GST (R = 0.3, P = 0.0048) and with GSH (R = 0.5, P = 0.0001) in tumor as wellas in normal tissue. GST activity was significantly higher in EBC than in LABCor metastatic breast cancer ( P = 0.02). GSH level was significantlyhigher in grade 1 than in grade 2 or grade 3 tumors ( P = 0.01). Whenclinical characteristics were related to the level of DRP, ‘high’ GSH wasassociated with age 〉60 years ( P = 0.01) in EBC, and with grade1–2 tumors ( P = 0.05) in LABC. No differences in OS were apparentbetween groups of ‘high’ and ‘low’ DRP-expression. However, the four-yearestimated disease-free survival of EBC tended to be higher in patients with‘high GST ( P = 0.10) and of LABC in patients with ‘high’ GPx levels( P = 0.06). Conclusion: We conclude that ‘high’ levels of DRP in tumor tissue ofbreast cancer patients are part of the initial phenotype of the malignantcells. Due to its high prevalence (83% in EBC, 100% in primarilymetastatic breast cancer), PGP did not add to prognostic information. Highlevels of GSH, GST and and GPx were associated with favorable clinicalcharacteristics and good prognosis, whereas low levels of GSH and GST activitywere associated with more aggressive or more advanced disease.
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  • 10
    ISSN: 1569-8041
    Keywords: breast cancer ; clinical efficacy ; endocrine activity ; vorozole
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Aminoglutethimide was the first aromatase inhibitor to beused successfully in breast cancer patients. However, this drug alsoinhibits mineralcorticoid and glucocorticoid synthesis, making co-medicationwith corticosteroids necessary, and it is often poorly tolerated. Theprimary objective of this trial was to evaluate the clinical efficacy andtolerability of vorozole, a new non-steroidal oral aromatase inhibitor, inpostmenopausal breast cancer patients. The secondary objective was toevaluate the pharmacodynamic activity of the drug. Subjects and methods: Thirty-four postmenopausal patients previouslytreated with tamoxifen in the adjuvant setting and/or for advanced diseasewere treated with vorozole, 2.5 mg once daily. Patients were monitored withrespect to treatment efficacy and safety. Hormonal evaluations wereperformed at baseline and during the course of treatment in order toevaluate the pharmacodynamic efficacy and safety of vorozole. Results: According to UICC criteria, there were seven responders, onecomplete and six partial, for an overall response rate of 21%(95% confidence interval (CI) 9%–38%). The medianduration of response was 9.6 months (95% CI 4.6–0), the mediantime to progression for the entire group was 4.7 months (95% CI2.9–6.6) and the median survival time was 29.7 months (95% CI19.1–0). Tolerability was excellent to good in 97% of thepatients. Oestradiol and oestrone levels were suppressed to the limit ofdetection of the assays used. No effect was observed on the other endocrineparameters. Conclusions: Our results suggest that vorozole is an effective and safedrug for the treatment of advanced postmenopausal breast cancer followingtamoxifen failure.
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  • 11
    ISSN: 1569-8041
    Keywords: breast cancer ; chemotherapy ; fluorouracil ; folates ; vinorelbine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Vinorelbine, is an active drug in the treatment of metastatic breast cancer and has a favorable toxicity profile. Its combination with other effective and well-tolerated cytotoxics may thus be beneficial. We investigated the therapeutic effect of a combination of vinorelbine plus 5-fluorouracil and folinic acid as first-line treatment in patients with metastatic breast cancer. Patients and methods: Forty-five patients with advanced or metastatic breast cancer were enrolled in this phase I–II study and treated with 5-fluorouracil (350 mg/m2 i.v. on day 1 to 3), folinic acid (100 mg/m2 i.v. on day 1 to 3) and vinorelbine given on days 1 and 3 at the dose of 25 mg/m2 (dose level 1), or 30 mg/m2 (dose level 2). Therapy was given on an outpatient basis every three weeks. Results: Phase I: Dose limiting toxicity (DLT) occurred at the second dose level of vinorelbine (30 mg/m2), with two out of three patients developing severe constipation (‘ileus-like syndrome’ grade 4), and fever (grade 2). Consequently, the dose evaluated in the phase II study was 25 mg/m2. Phase II: Objective responses were observed in 24 of 39 evaluable patients (95% confidence interval (95% CI), 47% to 77%). There were seven complete responses (18%), 17 partial responses (44%), and for nine patients (23%) disease was stable. Only six patients (15%) experienced disease progression. The median response duration was 10 months (range 6 to 24+) and the median time to progression was eight months (range 2 to 24+). Granulocytopenia was the most frequently observed side effect, with a grade 4 nadir being observed in 30 patients (77%), with four hospital admissions due to febrile neutropenia. Nausea, vomiting, and anorexia were mild to moderate and reported by less than half of the patients. Alopecia was moderate and occurred in about one-third of the patients. The other side effects were mild and easily manageable. Conclusions: This effective combination chemotherapy of vinorelbine, 5-fluorouracil and folinic acid is comparable to other first-line regimens in terms of efficacy, and is subjectively well tolerated, thus deserving a test in randomized trials in the advanced and adjuvant settings.
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  • 12
    ISSN: 1569-8041
    Keywords: adjuvant therapy ; breast cancer ; cross-cultural issues ; linear analogue self-assessment (LASA) scales ; quality of life ; randomized controlled trials
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background and purpose: The International Breast Cancer Study Group (IBCSG) has developed an approach for assessing the impact of adjuvant therapy on quality of life (QL) within the framework of international, multilingual clinical trials. The major steps are summarized. Conceptual, methodological and practical issues are discussed with reference to results of two trials closed to accrual (IBCSG VI, VII) and one subsequent ongoing trial (IBCSG IX). Patients and methods: QL was assessed in pre- and postmenopausal patients with operable breast cancer. Various single-item linear analogue self-assessment (LASA) scales were used as indicators of components of QL, including global indicators of well-being, functioning and health perception, and specific indicators of symptoms of disease and treatment. In trials VI and VII, QL was assessed at baseline, during adjuvant treatment and follow-up, and at recurrence. Based on this experience, the QL form was revised for subsequent trials and further investigated in a subsample of patients randomized into trial IX. Results: In trials VI and VII, the QL indicators were responsive to the impact of biomedical factors at baseline, various adjuvant treatments, changes over the first 18 months, and recurrence. In trial IX, the revised QL form was well accepted by patients and staff. Completing this form did not exceed five minutes. QL differences between on and off cytotoxic treatment strengthen the claim that these measures are responsive. Correlations and logistic regression analyses show the expected relationship among the various global and specific indicators. Conclusion: Results from two trials closed to accrual and an ongoing trial confirm the feasibility, validity and clinical relevance of the IBCSG approach for studying the impact of adjuvant breast cancer therapy on QL in international clinical trials.
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  • 13
    ISSN: 1432-1335
    Keywords: RT/PCR ; PTHrP ; Metastasis ; Blood ; Bone marrow ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Tumor cell dissemination in the bone marrow is an independent prognostic marker for relapse and survival for patients with primary breast cancer. Parathyroid-hormone-related protein (PTHrP) is expressed in most primary tumors and bone metastases of patients with breast cancer. PTHrP acts as an autocrine growth factor for breast cancer cells in vitro and there is evidence that it is especially important for osseous metastasis. For a sensitive detection of PTHrP-positive disseminated tumor cells a reverse transcriptase/polymerase chain reaction (RT/PCR) assay for PTHrP transcripts in the peripheral blood (PB) and in the bone marrow (BM) has been established. In mixing studies, the sensitivity of the reverse transcriptase/polymerase chain reaction (RT/PCR) for PTHrP was one tumor cell in 1×106 mononuclear cells. At this level of sensitivity, transcripts of PTHrP were detected in none of 30 PB samples and in 3 of 25 BM samples of healthy volunteers: there were also no transcripts of PTHrP in the PB and BM of 6 patients with benign breast lesions. The PB samples of 31 patients and the BM samples of 34 patients with predominantly early-stage breast cancer were tested for PTHrP expression along with immunocytology against cytokeratin 18 (CK18) as a standard immunological detection technique. PTHrP expression was shown in 9 of 31 patients in the PB and in 9 of 34 patients in the BM. In 30 patients, PB and BM samples were available simultaneously. There were cases of combined positive findings in the PB and the BM (4/30) and of isolated positivity in the PB (5/30) or in the BM (4/30). Compared to immunocytology, RT/PCR assay of PTHrP assay was significantly more sensitive in the peripheral blood (8/30 by RT/PCR compared to 1/30 by immunocytology). In the bone marrow there were cases of positivity for both markers (2/34), cases of isolated positivity by immunocytology for CK18 (3/34) and cases of isolated positivity for PTHrP transcripts (7/34). In conclusion the RT/PCR assay for PTHrP transcripts is a feasible and very sensitive technique for the detection of tumor cell dissemination in the PB, even in patients with early-stage breast cancer. The specificity of detection of PTHrP transcripts in the bone marrow is limited, possibly because of autochthonous expression of PTHrP in osteoblastic cells. The clinical follow-up of the subgroups of patients at risk, as defined by this assay, will show its prognostic significance for patients with breast cancer.
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  • 14
    ISSN: 1436-2813
    Keywords: breast cancer ; chemosensitivity ; bax ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Bax, one of thebcl-2 family genes, is expressed in a number of untransformed cell lines and various breast tissues, whereas only weak or no expression has been detected in breast cancer cell lines and malignant breast tissue. Human breast cancer MCF-7 cells, which have a weakbax gene expression, were stably transfected withpCX2neo bax, encoding humanbax; and two unique clones,MCF-7/bax-1 andMCF-7/bax-2, that expressed different levels ofbax were generated. Sensitivity to cisplatin (CDDP) and etoposide (VP-16) was examined and each stable transfectant was more sensitive to these agents than the parental MCF-7 cells. The degree of enhancement in sensitivity to these anticancer agents was dependent on the expression level ofbax. The enzyme-linked immunosorbent assay (ELISA), which quantifies DNA damage, demonstrated that this sensitization was due to apoptosis. Thus, we suggest that exogenousbax-α overexpression may be one of the factors determining cellular chemosensitivity in MCF-7 breast cancer cells and that it could be applied therapeutically to enhance chemosensitivity in breast cancer cells.
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  • 15
    ISSN: 1432-1335
    Keywords: Key words RT/PCR ; PTHrP ; Metastasis ; Blood ; Bone marrow ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Tumor cell dissemination in the bone marrow is an independent prognostic marker for relapse and survival for patients with primary breast cancer. Parathyroid-hormone-related protein (PTHrP) is expressed in most primary tumors and bone metastases of patients with breast cancer. PTHrP acts as an autocrine growth factor for breast cancer cells in vitro and there is evidence that it is especially important for osseous metastasis. For a sensitive detection of PTHrP-positive disseminated tumor cells a reverse transcriptase/polymerase chain reaction (RT/PCR) assay for PTHrP transcripts in the peripheral blood (PB) and in the bone marrow (BM) has been established. In mixing studies, the sensitivity of the reverse transcriptase/polymerase chain reaction (RT/PCR) for PTHrP was one tumor cell in 1 × 106 mononuclear cells. At this level of sensitivity, transcripts of PTHrP were detected in none of 30 PB samples and in 3 of 25 BM samples of healthy volunteers; there were also no transcripts of PTHrP in the PB and BM of 6 patients with benign breast lesions. The PB samples of 31 patients and the BM samples of 34 patients with predominantly early-stage breast cancer were tested for PTHrP expression along with immunocytology against cytokeratin 18 (CK18) as a standard immunological detection technique. PTHrP expression was shown in 9 of 31 patients in the PB and in 9 of 34 patients in the BM. In 30 patients, PB and BM samples were available simultaneously. There were cases of combined positive findings in the PB and the BM (4/30) and of isolated positivity in the PB (5/30) or in the BM (4/30). Compared to immunocytology, RT/PCR assay of PTHrP assay was significantly more sensitive in the peripheral blood (8/30 by RT/PCR compared to 1/30 by immunocytology). In the bone marrow there were cases of positivity for both markers (2/34), cases of isolated positivity by immunocytology for CK18 (3/34) and cases of isolated positivity for PTHrP transcripts (7/34). In conclusion the RT/PCR assay for PTHrP transcripts is a feasible and very sensitive technique for the detection of tumor cell dissemination in the PB, even in patients with early-stage breast cancer. The specificity of detection of PTHrP transcripts in the bone marrow is limited, possibly because of autochthonous expression of PTHrP in osteoblastic cells. The clinical follow-up of the subgroups of patients at risk, as defined by this assay, will show its prognostic significance for patients with breast cancer.
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  • 16
    Electronic Resource
    Electronic Resource
    Springer
    Annals of oncology 8 (1997), S. 223-225 
    ISSN: 1569-8041
    Keywords: breast cancer ; diet ; genistein ; isoflavones ; soybean ; tyrosine kinase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The study reviews the anticancer properties of naturalisoflavones which occur in especially high concentration in soybeans. Itconsiders the suitability of soybean products for clinical trials aiming toreduce the progression of breast cancer. Methods: Evidence is reviewed that plant isoflavones such asgenistein show cytostatic activity against human mammary cancer cell linesin vitro and can also suppress carcinogen-induced mammary cancer inyoung and mature rats. Results: Plant isoflavones are converted in the bowel to compoundswith potential antioestrogenic and antioxidative properties. These compoundsshow cytostatic activity for both oestrogen receptor-positive and negativehuman mammary cancer cell lines, and also inhibit growth and progress of therat mammary cancer model. The high content of soybean products in the diet ofAsian women has been postulated as one reason for their relatively low breastcancer incidence. Conclusion: Preclinical studies suggest that soybean products begiven priority for clinical trials in breast cancer protection. A pilot studycould test soy protein supplements as long-term adjuvant dietary treatmentafter primary surgery for early breast cancer, looking for a decrease in therisk of recurrence or of second primary tumours.
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  • 17
    ISSN: 1569-8041
    Keywords: breast cancer ; chemotherapy ; platelet-derived endothelial cell growth factor ; prediction ; thymidine phosphorylase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Thymidine phosphorylase (TP) catalyses the reversiblephosphorylation of thymidine to thymine and 2-deoxyribose-1-phosphate. Highexpression of TP in cell lines potentiates the effects of the cytotoxic drugs5-fluorouracil and methotrexate, both of which are used in thecyclophosphamide, 5-fluorouracil and methotrexate (CMF) treatment regimen ofbreast cancer. Patients and methods: We therefore examined the expression of thisenzyme in 328 invasive breast carcinomas using immunohistochemistry andassessed whether the expression of this enzyme by the tumour predicts patientresponse to CMF in node-positive patients. Results: Whereas no significant difference in either relapse-freesurvival (RFS) (P = 0.2) or overall survival (OS) (P = 0.07) wasobserved between TP-negative and -positive tumours in non-treated patients,there was a significant increase in both RFS (P = 0.02) and OS (P = 0.02) inpatients treated with CMF in TP-positive compared with TP-negativetumours. A multivariate analysis of the 134 node-positive patientsdemonstrated that in ductal carcinomas, TP was an independent variable for OS. Conclusions: This pilot study suggests that patients with TP-positivetumours have a significant survival benefit when treated with CMF and supportsthe hypothesis that TP enhances tumour sensitivity to the anti-metabolites5-fluorouracil and methotrexate.
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  • 18
    ISSN: 1569-8041
    Keywords: breast cancer ; conservative treatment ; local recurrence ; risk factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Risk factors for local recurrence after breast-conservingtreatment of early breast cancer have not previously been evaluated insettings where mammography has been a major pathway to diagnosis of bothprimary tumour and recurrences, or in patients treated surgically by a formalsector resection. Patients and methods: Three hundred eighty-one women with stage Iprimary breast cancer were randomised after a standardised sector resectionto either a course of postoperative radiotherapy to 54 Gy to the breast (XRTgroup) or to surgery alone (non XRT group). At five years, 43 localrecurrences, six of them in the XRT group, appeared. Patient characteristicscollected from the medical records, histopathological characteristicsdetermined by re-examination of slides, and mammographic characteristcs fromthe pre-operative mammograms were evaluated as risk factors for recurrence byunivariate and multivariate Cox proportional hazards models. Results arereported as relative hazards (RH) with 95% confidence intervals(95% CI). Results: In the univariate analysis comedo cancer, RH 3.5 (95%CI 1.8–6.7), lobular cancers RH 2.8 (95% CI 1.1–7.1),mammographic appearance as circular/oval shaped density, RH 2.3 (95%CI 1.1–4.5), and mammographic appearance as a stellate lesion withmicrocalcifications inside the lesion, RH 3.8 (95% CI 1.1–13.0)were identified as risk factors for local recurrence. Age, with a RH of 0.97(95% CI 0.94–0.99) for each increasing year was inverselyassociated with risk. A multivariate analysis, which also took postoperativeradiotherapy into account, only showed comedo cancers with a RH 2.6(95% CI 1.3–5.0) and mammographic appearance of a stellate lesionwith microcalcification inside the lesion RH 4.5 (95% CI1.1–17.6) to be statistically significant. The estimates for age RH 0.98(95% CI 0.95–1.0) and lobular cancers RH 2.5 (95% CI0.98–6.6) were marginally changed, with widened CIs. Patients 〉 60years of age, without comedo or lobular carcinomas were found to be at lowrisk (5.9% at five years in Kaplan–Meyer estimate) of localrecurrence, even without postoperative radiotherapy. Conclusion: Low age, comedo and lobular cancers and mammographicappearance of the tumour as a stellate lesion with microcalcifications insidethe lesion indicate an increased risk for local recurrence after sectorresection in stage I tumours at five years. Patients 〉60 years of agewithout comedo or lobular cancers are at low risk for local recurrence at fiveyears even without postoperative radiotherapy.
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  • 19
    ISSN: 1569-8041
    Keywords: advanced disease ; aromatase inhibitors ; breast cancer ; formestane
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: In postmenopausal breast cancer (BC) patients, tamoxifen (TAM)is frequently used in first-line therapy, and for those relapsing under TAM,aromatase inhibitors would be the drug of choice. Formestane, a new aromataseinhibitor, has been demonstrated to be as effective as TAM in first-linetherapy. This trial was carried out to investigate the pharmacokinetics andantitumor activity of two formestane doses in BC patients at first relapse,as well as their effects on estrogen levels, evaluated by means of a newanalytical method. Patients and methods: One hundred fifty-two postmenopausal BC patients wererandomly given formestane 250 mg or 500 mg intramuscularly every two weeks.The blood samples for estrogen measurements were taken on the first day oftherapy, at 4 and 10 weeks, and every 12 weeks thereafter. Tumor response wasfirst evaluated after 2.5 months, and then every three months. Results: Seventy-three patients received formestane 250 mg and 79 received500 mg. After four weeks, plasma estrone, estradiol and estrone sulphatelevels were significantly (P〈0.001) suppressed in both groups. The overallresponse rates were 30% and 40% on 250 mg and 500 mg,respectively. Conclusions: Both of the formestane doses are effective in reducing plasmaestrogen levels in BC patients at first relapse, and the new analytical methodimproved the quality of results. The antitumor response was highlysatisfactory.
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  • 20
    ISSN: 1569-8041
    Keywords: breast cancer ; cyclophosphamide ; G-CSF ; paclitaxel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The toxicity profile of prolonged infusions of paclitaxel incombination with cyclophosphamide in metastatic breast cancer has already beendefined. The objective of this dose-finding study was to determine the maximumtolerable doses (MTDs) of shorter (three-hour) infusions of paclitaxel incombination with i.v. bolus cyclophosphamide in patients who had previouslyreceived a maximum of one chemotherapy for advanced breast carcinoma. The MTDof the same regimen with granulocyte colony-stimulating factor (G-CSF) supportwas then established. Patients and methods: Eighty women with metastatic breast cancer receiveda total of 352 fully evaluable courses of therapy. The starting doses werepaclitaxel 135 mg/m2 and cyclophosphamide 750mg/m2 given every three weeks. At least three patients weretreated at each dose level and if there were dose-limiting toxic effectsduring the first cycles three additional patients were entered. G-CSF support(5µg/kg s.c.) was added to the second cycle if specific dose-limitingtoxicitieshad occurred during the first cycle. The MTD was defined as the dose level atwhich more than two of six patients presented dose-limiting toxicities duringthe first cycle. Results: Febrile neutropenia (n = 4) and severe thrombocytopenia (n = 1)defined the MTDs of paclitaxel as 200 mg/m2 and ofcyclophosphamide as 2,000 mg/m2, with or without G-CSF inpatients with and, respectively, without prior chemotherapy for advanceddisease. Non-hematologic toxicity was moderate. Recommended doses were 200mg/m2 of paclitaxel and 1,750 mg/m2 ofcyclophosphamide with or without G-CSF in patients with and, respectively,without prior chemotherapy. The overall response rate was 25% and50%, respectively, in patients with and without prior chemotherapy formetastatic disease. Complete remissions (9%) were reported only inpatients without prior chemotherapy; antitumour activity in women withanthracycline-resistant disease, with an 8% response rate (95%CI: 1%–26%), was poor. Conclusions: Paclitaxel at 200 mg/m2 and cyclophosphamideat 1,750 mg/m2 can be safely administered every three weeksto women with advanced breast cancer. The moderate antitumour activityobserved with the schedule tested argues against its use as initial therapyfor advanced breast cancer.
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  • 21
    ISSN: 1569-8041
    Keywords: breast cancer ; conservative treatment ; cost-effectiveness ; randomized trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Cost-effectiveness of routine postoperative radiotherapyafter breast-conserving surgery has not been prospectively evaluatedearlier. In times of rationing of medical resources, valid assessments ofcost-effectiveness are important for rational allocation of resources. Purpose: Cost and cost-effectiveness of routine postoperativeradiotherapy was calculated in a prospective randomized trial comparingsector resection plus axillary dissection with (XRT group) or without(non-XRT group) postoperative radiotherapy in breast cancer stage I. Threehundred eighty-one patients were included. After a median follow-up of fiveyears 43 local recurrences, six of them in the XRT-group occurred (P 〈0.0001). No difference in regional and distant recurrence (P = 0.23) orsurvival (P = 0.44) was observed. Patients and methods: Direct medical costs as well as indirect costs interms of production lost during the treatment period and travel expenseswere estimated from data in the medical records and the national insuranceregistry of each patient. Average costs of different treatment activitiesand measures were estimated for the XRT-group and the non-XRT grouprespectively. From these estimates differences in costs and effectivenessbetween the groups were calculated and marginal cost-effectiveness ratioswere estimated. For the construction of QALYs each life-year wasquality-adjusted by a utility value depending on which health state thepatient was considered to perceive. Results: Taking into account the cost of primary treatment, the cost offollow-up, the cost of treatment of a local recurrence, travel expenses andindirect costs (production lost) excluding costs for treatment of regionaland distant recurrence the cost per avoided local recurrence at five yearswas SEK 337,727 ($44,438, £27,018). Adjustment for quality of life showed a cost for every gained QALY to beSEK ∼1.6 million, ($210,526, £128,000), range SEK0.2–3.9 million ($26,315–513,158;£16,000–312,000). Conclusion: The cost of routine postoperative radiotherapy after sectorresection and axillary dissection in breast cancer stage I per avoided localrecurrence and gained QALY is high. The cost per gained QALY show greatvariation depending on utility value, which in this study was derived fromexternal observers and not from the patients themselves. These results stressthe importance of identifying risk factors for local recurrence, betterunderstanding of impact on quality of life of a local recurrence and addingcost evaluations to clinical trials in early breast cancer.
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  • 22
    ISSN: 1569-8041
    Keywords: adjuvant chemotherapy ; breast cancer ; menstrual cycle ; premenopausal ; surgery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: It has been postulated that breast cancer surgery performedduring the follicular phase of the menstrual cycle is associated with pooreroutcome. Patients and methods: We tested this hypothesis by evaluatingdisease-free survival (DFS) for 1033 premenopausal patients who receiveddefinitive surgery either during the follicular phase (n = 358) or theluteal phase (n = 675). All patients were enrolled in a randomized trialconducted between July 1986 and April 1993. All had node positive breastcancer and randomization was stratified by estrogen receptor (ER) status.All patients received at least three cycles of adjuvant cyclophosphamide,methotrexate, and 5-fluorouracil (CMF). The median follow-up was 60 months. Results: Patients who underwent definitive surgery for breast cancer inthe follicular phase had a slightly worse disease-free survival than thoseoperated on during the luteal phase (five-year DFS percentage: 53%versus 58%; hazard ratio, 1.13; 95% confidence interval (CI),0.94–1.38; P = 0.20). The effect was significantly greater for thesubpopulation of 300 patients with ER-negative primaries (P = 0.02interaction effect; five-year DFS percentages 42% vs. 59%;hazard ratio 1.60; 95% CI, 1.12–2.25; P = 0.008). The effect oftiming of surgery diminished for analyses based on lesser surgicalprocedures, e.g., excisional biopsies. In particular, no effect of timingwas observed for fine needle aspiration procedures. Conclusions: Surgical procedures which are more extensive than a fineneedle aspiration biopsy might be associated with worse prognosis if conductedduring the follicular phase of the menstrual cycle. This phenomenon was seenpredominantly for high risk breast cancer with low levels or no estrogenreceptors in the primary tumor.
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  • 23
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    Molecular and cellular biochemistry 167 (1997), S. 169-177 
    ISSN: 1573-4919
    Keywords: tamoxifen ; interferon ; gene expression ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The molecular basis for the enhanced growth inhibition of MCF-7 human breast cancer xenografts by a combination of human interferon-β (IFN-β) and tamoxifen was investigated. Treatment of MCF-7, MDA-MB-231, and BT-20 cells with the combination of IFN-β and tamoxifen resulted in enhanced antiproliferative effects in vitro. Treatment with the combination of IFN-β and tamoxifen enhanced the expression of several IFN-β-inducible genes in human breast carcinoma cell lines relative to levels induced by IFN-β alone. Tamoxifen alone did not induce transcription of IFN-stimulated genes (ISGs). Augmentation of ISG expression by the combination of IFN-β and tamoxifen was noted in breast tumor cell lines irrespective of their functional estrogen receptor (ER) status or their dependence on estradiol for growth, suggesting that upregulation of ISGs was independent of ER status. Enhancement of IFN-stimulated gene expression by tamoxifen occurred at the transcripti onal level. Expression of transfected reporter genes under the control of IFN-α/β regulated promoters was also enhanced in IFN-β and tamoxifen-treated cells. Similarly, transcriptional induction of chimeric reporter plasmids driven by an IFN-γ inducible promoter (GAS; IFN-γ activated site) was also enhanced by the combination of IFN-γ and tamoxifen. In tamoxifen treated cells, IFN-β and IFN-γ readily activated transcription factors ISGF-3 and GAF, respectively. Therefore, augmentation of ISG expression by tamoxifen is an early event in the antitumoral activity of this drug combination. (Mol Cell Biochem 167: 169-177, 1997)
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  • 24
    ISSN: 1573-4919
    Keywords: aurintricarboxylic acid ; breast cancer ; p53 tumor suppressor protein ; phenanthroline ; rifampicin ; T47D cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract We have investigated the influence of three structurally different but functionally related compounds [1, 10 ortho-phenanthroline (phenanthroline), Rifampicin and aurin tricarboxylic acid (ATA)] on the rate and the extent of proliferation of progesterone-responsive T47D human breast cancer cells. These compounds have previously been used in this laboratory and have been shown to modulate properties of nucleic acid binding proteins. Because p53 and the progesterone receptor (PR) are both DNA binding proteins that appear to regulate proliferation of breast cells, alterations in T47D cell p53 and PR levels were examined to determine their relevance in cell proliferation. T47D cells were grown in the absence of phenol red and in the presence of 5% fetal calf serum with or without charcoal stripping in the presence of the inhibitors. The rate of proliferation of cells grown in Rifampicin containing medium exhibited nearly 70% inhibition. Phenanthroline, a known metal chelator, was an effect ive inhibitor of proliferation at 3 mM reducing the cell number by more than 75%. ATA (0.24–2.4 µg/ml) inhibited the growth of the cells by nearly 50%. Analysis of the mechanism of action of these compounds revealed that treatment with these compounds caused specific changes in the molecular composition of T47D cell PR. Whereas ATA caused increased stability of PR isoforms, Rifampicin induced a upshift in the mobility of PR in SDS gels – a phenomenon associated with hyperphosphorylation of steroid receptors (SRs). Phenanthroline treatment (〉 2 mM) caused a complete down-regulation of PR and the tumor suppressor protein, p53. The downregulation of p53 paralleled the changes in the molecular composition of PR. We propose that the inhibition of T47D cell proliferation by phenanthroline, Rifampicin and ATA results from a number of cellular changes that include regulation of p53 and PR. (Mol Cell Biochem 175: 81–89, 1997)
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  • 25
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    European journal of nuclear medicine 24 (1997), S. 1167-1170 
    ISSN: 1619-7089
    Keywords: Technetium-99m furifosmin ; radionuclide imaging ; breast cancer ; ovarian cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recent in vitro studies suggest that technetium-99m furifosmin may have tumour-seeking properties. We analysed the diagnostic value of99mTc-furifosmin scintigraphy in nine patients with documented carcinoma of the breast and in eight patients with continued recurrent ovarian cancer. In the breast,99mTc-furifosmin failed to visualize the primary malignant tumour and the associated malignant lymph nodes in all patients. In contrast, multiple sites of increased tracer uptake were demonstrated in one patient with acute benign inflammatory breast disease. In four of eight patients with recurrent ovarian cancer,99mTc-furifosmin scintigraphy demonstrated early (5 min p.i.) localized increased uptake corresponding to adhesions to the bowel as diagnosed by computed tomography, but failed to reveal further abnormalities in all patients. The present study demonstrates that furifosmin is of no value in the imaging of breast cancer and recurrent ovarian cancer. These results do not continue the pattern observed in cell culture studies and are quite in contrast to the findings of mammoscintigraphy using99mTc-methoxyisobutylisonitrile and99mTc-tetrofosmin.
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  • 26
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    European journal of nuclear medicine 24 (1997), S. 1167-1170 
    ISSN: 1619-7089
    Keywords: Key words: Technetium-99m furifosmin ; radionuclide imaging ; breast cancer ; ovarian cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Recent in vitro studies suggest that technetium-99m furifosmin may have tumour-seeking properties. We analysed the diagnostic value of 99mTc-furifosmin scintigraphy in nine patients with documented carcinoma of the breast and in eight patients with continued recurrent ovarian cancer. In the breast, 99mTc-furifosmin failed to visualize the primary malignant tumour and the associated malignant lymph nodes in all patients. In contrast, multiple sites of increased tracer uptake were demonstrated in one patient with acute benign inflammatory breast disease. In four of eight patients with recurrent ovarian cancer, 99mTc-furifosmin scintigraphy demonstrated early (5 min p.i.) localized increased uptake corresponding to adhesions to the bowel as diagnosed by computed tomography, but failed to reveal further abnormalities in all patients. The present study demonstrates that furifosmin is of no value in the imaging of breast cancer and recurrent ovarian cancer. These results do not continue the pattern observed in cell culture studies and are quite in contrast to the findings of mammoscintigraphy using 99mTc-methoxyisobutylisonitrile and 99mTc-tetrofosmin.
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  • 27
    ISSN: 1573-7276
    Keywords: annexin ; breast cancer ; calcium-binding protein ; cell surface ; immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Annexins are a family of structurally related, water-soluble proteins that have calcium- and phospholipid-binding domains. Annexin I is thought to be involved in cell proliferation and differentiation and has recently been shown to be expressed on the surfaces of lymphoma cells where it acts as an endothelial cell adhesion molecule. To evaluate the expression of annexin I in relation to human breast cancer development and progression we used breast biopsy tissues. Immunohistochemical analysis of annexin I in paraffin-embedded ductal epithelial cells of various human breast tissues indicated that this annexin was not demonstrable in the ductal luminal cells of normal breast tissues (n = 11) and benign tumors (n = 10) (except for one ductal adenoma) but was generally expressed in various types of breast cancers, including noninvasive ductal carcinoma in situ (DCIS), invasive and metastatic breast tumors (n = 33). The results suggest that annexin I expression might correlate with malignant breast cancer progression but it is most likely involved at an early stage of human breast cancer development.
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  • 28
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    Journal of neuro-oncology 35 (1997), S. 161-167 
    ISSN: 1573-7373
    Keywords: brain metastasis ; breast cancer ; surgery ; radiotherapy ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Twenty-eight consecutive patients with breast cancer were analyzedwho presented with a single brain metastasis asfirst site of distant metastasis. The response tosurgery with postoperative radiation therapy (RT) (9 patients)and to non-surgical therapy as first-line treatment was100% and 89% respectively with a significant differencein median recurrence-free intervals of 23 months andof 5 months respectively (p=0.033). Retreatmentof a local relapse by surgery (± RT,± chemotherapy) or by non-surgical treatment resulted ina response in 6 of the 7 operatedpatients and in 5 of the 6 non-operatedpatients with a median duration of response of7 months (range 2–20 months) and of 3months (range 2–4 months) respectively. The overall mediansurvival of the 28 patients with a singlebrain metastasis was 16 months (range 2–39 months).The median survival in the primarily operated patientswas 23 months, in the primarily not-operated group10 months, and in the never-operated group 9months. In comparison, the response to non-surgical treatmentin 20 consecutive patients who presented with multiplebrain metastases as first site of distant metastasiswas 55% with a median recurrence free intervalof 4 months. The median survival in thisgroup was 4 months, which was significantly shorterthan survival of patients with single brain metastasis(p=0.0036). These results suggest that breastcancer patients with a single brain metastasis asfirst presentation of relapse constitute a specific subgroupwith a favorable response to treatment and along survival especially if they can be treatedby surgery with postoperative RT.
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  • 29
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    Journal of neuro-oncology 35 (1997), S. 55-64 
    ISSN: 1573-7373
    Keywords: breast cancer ; carainomatous meningitis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose. To identify the factors predictive of response and increasedsurvival in patients with leptomeningeal metastases (LM) from breast cancerreceiving multi-modal therapy. Background. Leptomeningeal metastases (LM)are being diagnosed with increasing frequency as anti-cancer therapiesbecome more effective and result in prolonged patient survival. Patients andmethods. 32 women (range 28 to 74 years; median 49) with LM due tometastatic breast cancer were treated. Neurologic presentation included:cranial neuropathies (10 patients); headache (10); cauda equina syndrome(6); ataxia (6); meningismus (3); radioculopathy (2); myelopathy (2);confusion (2); and seizure (1). All patients underwent radiographicevaluation of the extent of CNS disease followed by radiotherapy (21 women)and intraventricular chemotherapy: (methotrexate 32 women; cytarabine 22;thio-TEPA 11). Results. CNS imaging (cranial MR, spine MR and radionuclideventriculography) demonstrated: interrupted CSF flow (21); subarachnoidnodules (8); parenchymal brain metastases (6); hydrocephalus (4); andepidural spinal cord compression (1). Cytologic responses were seen in 14women to first-, 7 to second- and 3 to third-line chemotherapy.Treatment-related toxicity included 21 women with aseptic meningitis and 10women with thrombocytopenia or neutropenia (5 related to intraventricularchemotherapy). Median survival was 7.5 months (range 1.5 to 16). 18 womendied of progressive LM or combined LM and systemic disease progression.Women with persistent interruption of CSF flow fared worse than women withnormal CSF flow (median survival 3 versus 10 months; p 〈 0.0001).Conclusion. LM in women with metastatic breast cancer may be palliated withcombined modality therapy, however, success of therapy and survival is basedupon pre-treatment CNS extent of disease evaluation.
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  • 30
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    International journal of sexuality and gender studies 2 (1997), S. 101-121 
    ISSN: 1573-8167
    Keywords: femininity ; breast cancer ; lesbian identity ; health care ; homophobia ; heterosexism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Sociology
    Notes: Abstract The author discusses writings by Eve Kosofsky Sedgwick, Kathleen Martindale, Audre Lorde, and Barbara Rosenblum on their experiences with breast cancer, and explores their articulations of the impact mastectomy has had on their sense of “femininity” in relation to their own identities and body images, and in relation to cultural expectations, and how others perceive them. Their identification of the body as socially produced, and as a site of contestation and multiple struggles, offers a strategic site from which to engage with the violent gender-inflected notion of the “ideal” female body. Themes addressed include: the process of writing embodied experience to make it real, the body's role in the process of identity formation, the culturally constructed significance of appearance to the individual's sense of “femininity,” the value of the female body in a capitalistic society, and heterosexism in society and in the health care system.
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  • 31
    ISSN: 1573-7225
    Keywords: Abortion ; breast cancer ; pregnancy ; women
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To evaluate the relationship between breast cancer risk and spontaneous and induced abortion, we conducted a detailed descriptive review of 32 epidemiologic studies that provided data by type of abortion and by various measures of exposure to abortion-number of abortions, timing of abortion in relation to first full-term pregnancy, length of gestation, and age at first abortion. Breast cancer risk did not appear to be associated with an increasing number of spontaneous or induced abortions. Our review also suggested that breast cancer risk probably was not related to the other measures of exposure to abortion, and probably did not differ by age or a family history of breast cancer. Finally, the data appeared to suggest a slightly increased risk among nulliparous women, but this tendency was based primarily on studies with a small number of nulliparous women who had had spontaneous or induced abortions. Definitive conclusions about an association between breast cancer risk and spontaneous or induced abortion are not possible at present because of inconsistent findings across studies. Future investigations should consider prospective designs, separate analyses of spontaneous and induced abortions, appropriate referent groups, and adequate adjustment for confounding and effect modification. Future investigations also should attempt to determine whether any increased risks reflect the transient increase in breast cancer risk hypothesized for full-term pregnancy or a causal relationship specific to spontaneous or induced abortion.
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  • 32
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    Journal of medical systems 21 (1997), S. 303-307 
    ISSN: 1573-689X
    Keywords: automated mammography system ; breast cancer ; Computer Aided Diagnostic tool
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Automated processing of mammograms has been studied for several years. Until the last few years much of the efforts have produced marginal results due to the limitations of inexpensive hardware. Even with the advanced hardware no one has yet taken an entire mammogram and determined whether it is normal or abnormal. We outline a method here to attempt to do just that.
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  • 33
    ISSN: 1573-7217
    Keywords: affinity ; breast cancer ; estradiol ; receptor ; tissue estrogen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Breast tumors from postmenopausal women contain levels of estradiol similar to those in premenopausal patients even though serum estradiol levels fall by an order of magnitude upon cessation of ovarian function. The present study sought to examine enhanced uptake from plasma as one potential mechanism for maintenance of high tissue estradiol levels in postmenopausal patients. Accordingly, we used osmotic minipumps to continuously infuse estradiol (E2) at rates producing serum concentrations ranging from pre- to postmenopausal levels for two weeks to oophorectomized Sprague-Dawley rats bearing nitrosomethylurea-induced mammary tumors. We then measured E2 concentrations in various tissues and sera and reasoned that tissue affinities for estradiol could be directly calculated from in vivo measurements by adapting Scatchard analysis to steroid infusion data. Using this method, we demonstrated a very high affinity estradiol binding component with a Kd two orders of magnitude higher (i.e., 0.35 × 10-12 M) than determined with standard in vitro techniques. A second estradiol binding component with the expected Kdd of 1 × 10-10 M was also present. Estradiol bound to both classes of binding sites could be 98% displaced with diethylstilbestrol within a 6-hr period. In vivo steroid binding off-times calculated from log-linear slopes averaged approximately 60 min. These data demonstrated that the actual E2 binding affinity in target tissues in vivo, especially at low estrogen concentrations, is much higher than usually estimated from standard, in vitro estrogen receptor assays. These observations provide one mechanism to explain why estradiol concentrations remain high in breast cancer tissue from postmenopausal women and consequently can stimulate tumor proliferation.
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  • 34
    ISSN: 1573-7217
    Keywords: breast cancer ; elderly cancer patients ; age-related treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The medical records of all women (297 cases)with breast cancer ≥ 70 years of age,presenting at our Institute from January 1980 toDecember 1989, were reviewed. Data from 226 elderlywomen was compared to that from 100 stage-matchedpatients ≤ 50 years of age, presenting duringthe same 10-year study interval. Conservative surgery wassignificantly more frequent in young patients (71.1%) comparedto elderly women (26.1%) and radical mastectomy accordingto Halsted was undertaken in 34.3% of theelderly group compared to 8.9% of young patients(p 〈 0.001). Since ‘incidental’ diagnosis was significantlymore frequent in the elderly group (59.9% versus6.0%) (p 〈 0.001), primary care physicians mayplay an important role in the early diagnosisof breast cancer in the majority of elderlywomen.
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  • 35
    ISSN: 1573-7217
    Keywords: breast cancer ; ipsilateral breast tumor recurrence ; partial mastectomy ; radiotherapy ; risk factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To identify risk factors associated with an increasedrisk for ipsilateral breast tumor recurrence following breast-conservingsurgery, a cohort of 759 women with T1–T2tumors were studied. The majority of the patients(88%) had received postoperative radiation therapy to thebreast. Median follow-up time was 10 (range: 6–17)years. There was a 1–1.5% yearly increase inipsilateral breast tumor recurrences. For women 〈 50ys the cumulative recurrence rate at 10 yearswas 18% and for women ≥ 50 ys,9%. Node positive women had a cumulative breastrecurrence rate of 25% versus 10% for nodenegative women. Ten years postoperatively, irradiated patients hada cumulative recurrence rate of 11% versus 26%when no irradiation was given. The beneficial effectof radiotherapy was substantial during the first fourpostoperative years. The relative risk for an ipsilateralbreast tumor recurrence during this period was 4.5times higher than for non irradiated patients. However,the protective effect of radiotherapy decreased with time.After ten years the relative risk of ipsilateralbreast tumor recurrence was the same among irradiatedand non-irradiated patients although the number of eventsduring this period was low.Univariate analysis showed that seven factors were significantlyassociated with an increased risk of ipsilateral breasttumor recurrence, namely age 〈 50 ys, increasingtumor size, uncertain microscopic margins, axillary lymph nodemetastases, no postoperative tamoxifen treatment, premenopausal status, andno postoperative radiotherapy. Three factors remained independently significantafter multivariate analysis: age 〈 50 ys,no postoperative radiation therapy, and positive lymph nodes.In conclusion, radiotherapy reduced the breast recurrence rate,but the effect decreased with time. Node-negative women≥ 50 were a low risk-group for ipsilateralbreast tumor recurrence, with a cumulative risk at10 years of 9% without radiation therapy and5% with breast irradiation.
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  • 36
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    Breast cancer research and treatment 43 (1997), S. 33-41 
    ISSN: 1573-7217
    Keywords: breast cancer ; health services research ; small-area analysis ; tamoxifen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To describe the change in use oftamoxifen over time and across countries in Ontario.Methods: Data from the Ontario Drug Benefit (ODB)plan, Census Canada, and the Ontario Cancer Registry(OCR) were combined and analysed to determine ratesof tamoxifen use for females over 65 foreach county and the province overall, by year.Rates were analyzed by repeated measures ANOVA todetermine significance of changes over time. Consistency oftamoxifen use across counties was determined by theSpearman rank correlation coefficient, and overall variation betweencounties was described using three statistical techniques: Chi-squareanalysis, the extremal quotient (EQ), and the systematiccomponent of variation (SCV). Results: The number ofone-month tamoxifen prescriptions per incident case of breastcancer rose significantly from 13.51 in 1985 to20.54 in 1990 (p 〈 0.001) and to34.06 in 1992 (p=0.001). Viewed differently,the number of women over 65 receiving tamoxifenprescriptions per incident case of breast cancer changedfrom 1.91 in 1985 to 3.14 in 1990to 4.54 in 1992. Statistically significant variation inthe rate of tamoxifen prescribing was demonstrated betweenOntario counties in all three years by ChiSquared analysis (p 〈 0.0001). Both the EQand the SCV declined from 1985 to 1990,suggesting more uniform prescribing across the province. Littlechange in overall variation was seen between 1990and 1992. All counties over time tended toprescribe generic preparations more often and shifted from10 mg to 20 mg formulations. Conclusions: Thesignificant increase in the rate of tamoxifen useand trend towards more uniform prescribing across Ontariobetween 1985 and 1990 coincided with the publicationof two important documents outlining the benefits oftamoxifen in early breast cancer. Despite this trend,variation in tamoxifen use between counties remains. Therehas been little change in uniformity of prescribingsince 1990.
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  • 37
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    Breast cancer research and treatment 43 (1997), S. 211-215 
    ISSN: 1573-7217
    Keywords: breast cancer ; tumor necrosis factor ; mastectomy ; prognosis ; serum markers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The outcome of breast cancer is usuallydetermined by multiple factors. Serum tumor necrosis factoralpha concentration has been found to be increasedin the circulation of patients with malignancy. Thisstudy was designed with the aim to investigateany correlation between the serum tumor necrosis factoralpha and the clinicopathological fetures and furthermore evaluatethe prognostic significance of serum tumor necrosis factoralpha concentration in breast cancer. Methods: Forty consecutivepatients with invasive breast cancer undergoing modified radicalmastectomy were prospectively included and evaluated. Venous bloodsamples were collected before the surgery. Sera wereobtained by centrifugation, and stored at − 70°C until assayed. The control group consisted 30healthy, age-matched subjects. Serum concentrations of tumor necrosisfactor alpha were measured by the quantitative sandwichenzyme immunoassay technique. The data on tumor size,age, estrogen receptor status, lymph node status andTNM staging were reviewed and recorded.Results: The mean value of serum tumor necrosis factor alphain patients with invasive breast cancer was 1.47± 0.58 pg/ml and that of the controlgroup was 0.98 ± 0.37 pg/ml, and thedifference was significant (P 〈 0.01). With univariableanalysis, patients with maximum tumor size of 5cm or larger (P=0.03), more advancedTNM staging (P 〈 0.01); and more advancedlymph node status (P 〈 0.01) were shownto have significantly higher serum concentrations of tumornecrosis factor alpha. However, with multivariable analysis, TNMstaging appeared as the only independent factor (P〈 0.01) predicting the significant, higher serum concentrationsof tumor necrosis factor alpha. Conclusion: Preoperative evaluationof serum tumor necrosis factor alpha concentrations maybe a valuable parameter for reflecting the severityof staging for invasive breast cancer.
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  • 38
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    Breast cancer research and treatment 43 (1997), S. 225-235 
    ISSN: 1573-7217
    Keywords: breast cancer ; axillary lymph node dissection ; adjuvant radiotherapy ; responsible hospital ; survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A retrospective review is presented of 1353 consecutivepatients with histopathologically confirmed invasive breast carcinoma treatedradically with curative intent during the decade 1980–89.None had received adjuvant systemic therapy with hormonesor prolonged chemotherapy. The distribution of lymph-node negative(N−) and lymph-node positive (N+) patients was 75%and 25%, respectively. The treatment and outcome were analysed as regardsconventional prognostic parameters, in particular considering the axillarylymph-node status and the responsible hospital category (GeneralMunicipal Hospitals (MH)) versus Comprehensive Cancer Center (CC)). The most striking difference was detected as regardsthe number of examined lymph nodes. The mediannumber of nodes described at the MH was7, as compared to 14 at the CC(p 〈 0.001). In patients with pT1 tumoursthe highest rate of lymph-node positivity was observedwhen 10 or more axillary nodes were removed.Adjuvant radiotherapy reduced the loco-regional recurrence rate inthe N− patients, whereas only the regional recurrenceswere reduced among the N+ patients. The five-and 10-year tumor-related survival rates were 86% and76%, respectively, with no difference between the MHand the CC. As life-prolonging adjuvant hormone therapy and chemotherapy isnow available for patients with axillary lymph nodemetastases, it is important that patients with breastcancer are operated adequately with the aim toremove at least 10 axillary lymph nodes. Athorough examination of the axillary content should beperformed by the pathologist, and the number ofresected lymph nodes and metastases should be reported.The establishment of nation-wide standard criteria for themanagement of breast cancer is recommended.
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  • 39
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    Breast cancer research and treatment 44 (1997), S. 83-89 
    ISSN: 1573-7217
    Keywords: breast cancer ; capillary gas chromatography ; postmenopausal women ; urine steroids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Urinary steroid metabolites were measured by capillary gaschromatography in 22 postmenopausal women with operable breastcancer on day before the tumour excision andin 20 hospitalised control who were before anoperation from other cause than cancer. Serum dehydroepiandrosterone-sulphat(DHEAS) and testosterone (T) level were measured byradioimmunassay in the same groups and same time.There was no significant difference in the levelof urinary androgen metabolites. Pregnanediol level was significantlylower (P 〈 0.05) in cancer patients. Inthe 5 patients with positive axillary nodes thetetrahydrocortisol and α-cortolone levels were significantly (P 〈0.05) higher than in node negative ones. Therewas no significant differences in the serum DHEASand T levels. These results indicate that metabolicchanges are existing in postmenopausal patients which maybe a cause or a consequence of thedisease.
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  • 40
    ISSN: 1573-7217
    Keywords: CD44v6 ; breast cancer ; patients N0M0 ; metastasis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract New isoforms of CD44 with alternatively spliced exons have recently been described. Expression of exon v6 seems to be of particular interest. It has indeed been associated with poorer outcome of breast cancer patients with node invasion at diagnosis. However, no data were available for patients N0M0 (with neither metastasis nor node invasion at diagnosis). Moreover, previous statistical analyses were realized using immunohistochemical methods to detect CD44v6 expression although several variants with exon v6 have been described. We investigated expression of isoforms containing CD44v6 using an RT-PCR approach and a panel of 25 normal breast specimens, 10 mammary fibroadenomas, 8 cystic samples and 52 primary breast tumors (38 invasive N0M0). Normal breasts, fibroadenomas, and cysts all express the same variant, A (with exon v6 only), while several transcripts are amplified in tumors. Expression of variants other than A correlates with acquisition of a malignant phenotype. Invasive cancers also express additional variants in comparison with in situ carcinomas. Metastasis capacities seem to be associated with transcription of variants other than A but also with no transcription of some of them, variants D (with exons v6 and v10) and L (with exons v6 to v10). Expression of variants D and L correlates with higher percentages of disease-free survival and better outcome. Expression of CD44 splice variants with exon v6, as detected by RT-PCR, might be a useful prognostic factor for breast cancer. However, since the series size is small, our results need to be confirmed by later studies on a larger number of patients.
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  • 41
    ISSN: 1573-7217
    Keywords: breast cancer ; dehydroepiandrosterone sulfate ; estradiol ; postmenopausal Japanese ; progesterone ; sex hormone-binding globulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We measured serum levels of estradiol (E2), sex hormone-binding globulin (SHBG), progesterone, and dehydroepiandrosterone sulfate (DHEAS) in 61 postmenopausal women drawn from female residents in a community in Japan to evaluate the relationships between these hormone levels and potential breast cancer risk factors. The information on reproductive history, body size, alcohol use, and physical activity was obtained by means of a self-administered questionnaire. There was a significant trend in increasing E2 level with increasing height after taking account of age and body mass index (BMI) (p for trend = 0.04). BMI was inversely associated with SHBG level after controlling for age (p for trend = 0.01). Decreasing progesterone with increasing BMI was observed after controlling age and history of hysterectomy (P=0.05). Alcohol consumption was positively associated with E2 level and there was a strong linear trend after controlling for age, height, and BMI (p for trend=0.001). Trend for increasing DHEAS with alcohol consumption was also statistically significant after controlling for age and history of hysterectomy (p for trend=0.01). Reproductive factors as well as physical activity were not related to any of the hormone levels.
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  • 42
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    Breast cancer research and treatment 45 (1997), S. 07-14 
    ISSN: 1573-7217
    Keywords: breast cancer ; lumpectomy ; mastectomy ; QALY ; cost-utility
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the last decade, breast cancer patients have enjoyed an increase inbreast conserving surgery (BCS). At present, modified radical mastectomy(MRM) and BCS offers equal expectations of survival. During the last fewyears, however, a drop in the frequency of BCS has been reported by severalauthors. Is this new trend due to economic concerns? To clarify the costs ofbreast cancer therapy (stage I and II), we review the literature and includea cost-utility and a cost-minimisation analysis comparing MRM and BCS. The treatment cost (per patient) of BCS and MRM in Norway was calculated at$ 9,564 and $ 5,596, respectively. Employing a quality of lifegain in BCS of 0.03 (0–1 scale) and a 5% discount rate, thecost per QALY in BCS compared to MRM was $ 20,508. In cost-minimisinganalysis, BCS and mastectomy followed by reconstructive surgery had a costof $ 10,748 and $ 8,538, respectively. This indicates that BCSremains within reasonable cost and should not be displaced by mastectomy oneconomic grounds.
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  • 43
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    Breast cancer research and treatment 42 (1997), S. 121-124 
    ISSN: 1573-7217
    Keywords: Hispanics ; breast cancer ; ethnicity ; socioeconomic status
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the Department of Defense health care system,all women have the same ability to accesshealth care. Thus, there should be no racialdifferences in stage at diagnosis solely based onability to seek health care. A retrospective reviewof breast cancer cases from 1980–1992 was conductedto determine if there were any differences instage at diagnosis between Caucasian and Hispanic females.Data was available for 6134 Caucasian and 182Hispanic females. Although not statistically significant, Hispanic femaleshad fewer Stage I (41% versus 53%) andmore Stage IIA (37% versus 28%) breast cancersthan Caucasian females. Hispanic females had statistically fewertumors ≤ 1 cm (p 〈 0.001). Caucasianfemales were older (median age 58 years) atpresentation than Hispanic females (median age 51 years).Significantly (p = 0.002) more Hispanic females (44%)were 〈 50 years old compared to Caucasianfemales (28%). When access to care is notan issue, Hispanic females tended to present ata more advanced stage although this did notreach statistical significance. Hispanic females with breast cancerwere significantly younger than Caucasian females.
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  • 44
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    Breast cancer research and treatment 45 (1997), S. 81-95 
    ISSN: 1573-7217
    Keywords: breast cancer ; TGFβ ; activation ; resistance ; receptors ; tamoxifen ; chemoprevention
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Transforming Growth Factor-β (TGFβ) is the most potent knowninhibitor of the progression of normal mammary epithelial cells through thecell cycle. During the early stages of breast cancer development, thetransformed epithelial cells appear to still be sensitive toTGFβ-mediated growth arrest, and TGFβ can act as an anti-tumorpromoter. In contrast, advanced breast cancers are mostly refractory toTGFβ-mediated growth inhibition and produce large amounts of TGFβ,which may enhance tumor cell invasion and metastasis by its effects onextracellular matrix. We postulate that this seemingly paradoxical switch inthe responsiveness of tumor cells to TGFβ during progression is theconsequence of the activation of the latent TGFβ that is produced anddeposited into the tumor microenvironment, thereby driving the clonalexpansion of TGFβ-resistant tumor cells. While tumor cells themselvesmay activate TGFβ, recent observations suggest that environmental tumorpromoters or carcinogens, such as ionizing radiation, can cause stromalfibroblasts to activate TGFβ by epigenetic mechanisms. As thebiological effects of the anti-estrogen tamoxifen may well be mediated byTGFβ, this model has a number of important implications for the clinicaluses of tamoxifen in the prevention and treatment of breast cancer. Inaddition, it suggests a number of novel approaches to the treatment ofadvanced breast cancer.
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  • 45
    ISSN: 1573-7217
    Keywords: breast cancer ; chemotherapy ; mitoxantrone ; fluorouracil ; folinic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In this phase II trial we have evaluatedthe activity and toxicity of a combination regimencontaining mitoxantrone, L-leucovorin, and fluorouracil in patients withadvanced breast cancer pretreated with anthracyclines. Forty-six patientswere included into the study; they received atotal of 227 cycles of chemotherapy. Median agewas 63 years (range 34–78), median performance statuswas 80 (range 60–100). Visceral metastases were presentin 37 patients, 6 patients had bone involvementonly, while 3 patients had soft tissue/lymph nodedisease. Median number of previous chemotherapy regimens foradvanced disease was 2 (range 1–3). Ten patientshad anthracycline primary resistance (progressive disease during treatment).Twenty-three patients received mitoxantrone 12 mg/sqm day 1;fluorouracil 370 mg/sqm and L-folinic acid 100 mg/sqmdays 1–3 administered every three weeks. Another groupof 23 patients were treated with the sameregimen using a prolonged 5FU/L-FA schedule (5 days).Two complete responses and 6 partial responses wererecorded with the 3-day schedule; 7 partial responsesin the 5-day schedule (overall response rate 32.6%,95% C.I. 19–46%). Two partial responses were observedin patients with anthracycline primary resistance. Median responseduration was 9 months (range 3–16). Hematologic toxicitywas mild: grade 3–4 leukopenia was recorded in5 patients, grade 3–4 thrombocytopenia in 3 patients.Grade III–IV stomatitis and diarrhea was recorded in4 and 5 patients respectively (all receiving the5-day 5-FU/L-FA schedule). Cardiac toxicity was observed intwo cases. This regimen proved active in advancedbreast cancer following anthracycline-containing chemotherapy, and the 3-dayschedule could be offered to such patients withacceptable toxicity.
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  • 46
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    Breast cancer research and treatment 46 (1997), S. 255-278 
    ISSN: 1573-7217
    Keywords: xenografts ; breast cancer ; cell lines ; resistance ; cytotoxic drugs ; synergy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Considerable effort has been placed into the identification of new antineoplastic agents to treat breast cancer and other malignant diseases. The basic approaches, in terms of model selection, endpoints, and data analysis, have changed in the previous few decades. This article deals with many of the issues associated with designing in vivo studies to investigate the activity of experimental and established compounds and their potential interactions. Endpoints for both in situ and excision assays are described, including approaches for determining cell kill, tumor growth delay, survival, and other estimates of activity. Suggestions for approaches that may limit the number of animals also are included, as are possible alternatives for death as an experimental endpoint. Other concerns, such routes for drug administration, drug dosage, and preliminary assessments of toxicity also are addressed. Statistical considerations are only briefly discussed, since these are addressed in detail in the accompanying article by Hanfelt (Hanfelt JJ, Breast Cancer Res Treat 46:279-302, 1997). The approaches suggested within this article are presented to draw attention to many of the key issues in experimental design and are not intended to exclude other approaches.
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  • 47
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    Breast cancer research and treatment 46 (1997), S. 215-223 
    ISSN: 1573-7217
    Keywords: breast cancer ; monounsaturated fats ; n-3 fatty acids ; n-6 fatty acids ; saturated fats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We review two meta-analyses of experiments on dietary fat and mammary tumor incidence in rodents, emphasizing a recent meta-analysis on the effects of different types of dietary fatty acids. This analysis shows that n-6 polyunsaturated fatty acids most strongly enhance mammary tumors in rodents, and saturated fats also enhance these tumors but less strongly. Further, the analysis shows that energy restriction protects against mammary tumors. We show that these results agree qualitatively with estimates of effects on human breast cancer derived from international correlations.
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  • 48
    ISSN: 1573-7217
    Keywords: breast cancer ; invasion ; zymography ; MMP-9
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The degradation of the basement membrane by matrix-metalloproteinase(MMP) and serine protease is a critical pointin tumor invasion and metastasis. We measured theactivity of MMP-9 from 28 normal, 12 benignand 126 breast cancer tissues using gelatin zymographywith an image analysis system. ProMMP-9 was expressedin 17.5% of the cancer patients compared to2.5% in 40 non-cancerous tissues (p=0.014).The mature form of MMP-9 (82 kD) wasexpressed only in T2–T4 stages. During the earlyphase of breast cancer (DCIS and T1 stage)progression, only production of proMMP-9 increased. However, asthe cancer grew or invaded skin (T2–T4), orwith lymphovascular permeation, both production and activation ofMMP-9 increased. In conclusion, proMMP-9 production was themain cause of increased MMP-9 activity during theearly phase, while both production and activation increasedin the late phase of breast cancer.
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  • 49
    ISSN: 1573-7217
    Keywords: breast cancer ; metastatic ; filgrastim ; mitoxantrone ; 5-fluorouracil ; leucovorin ; chemotherapy ; CSFs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Based on reports of substantial antitumor efficacy of the combination of mitoxantrone (DHAD), 5-fluorouracil (FU) and leucovorin (LV), a clinical trial was performed to attempt augmentation of the dose of DHAD with filgrastim support. The doses and schedules, all intravenous, were DHAD (total dose divided over days 1 and 2), level I, 16 mg/m2; II, 20 mg/m2;III, 24 mg/m2; IV, 32 mg/m2;and LV, 300 mg, followed by FU, 350 mg/m2;,on days 1–3. Filgrastim was given at 5 μg/kg/day subcutaneously on days 4–13. The planned cycle length was 21 days. Three or 4 patients were to be entered at each dose level and the maximum tolerated dose (MTD) was defined as thedose immediately below that which resulted in 2 patients with dose-limiting toxicity (DLT) in cycle 1. Once an apparent MTD was identified, an additional 6 patients were to be entered. Twenty patients (pts) were entered: level I: 3 pts; II: 3 pts; III: 10 pts; IV: 4 pts. The major toxicity was found to be cumulative thrombocytopenia with platelet counts ≤ 20,000/μL occurring after cycle 1 at all levels beyond level I and five pts (25%) were removed from treatment solely because of platelet toxicity. Additional serious toxicities included grade 4 stomatitis in one patient (level IV) and cardiac toxicity in 2 patients with prior doxorubicin exposure. Ten pts had measurable and 8 had evaluable disease, and in 17 pts assessed, 5 (29%)achieved an objective response. The response rates in this study are lower than reported in the literature for the combination of DHAD, 5FU, LV and this may be related to the fact that only 40% of the patients were removed from protocol treatment because of disease progression. On the basis of limited DHAD-dose augmentation, toxicities observed, and modest response rate, the filgrastim-supported DHAD, 5FU, LV regimen as utilized in this study cannot be recommended for further development for treatment of women with metastatic breast cancer.
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  • 50
    ISSN: 1573-7217
    Keywords: age at first full-term pregnancy ; breast cancer ; etiological risk factors ; family history ; oral contraceptives ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Several risk factors for the etiology of breastcancer have also been correlated with the prognosisof breast cancer. However, the published studies haveyielded conflicting results. Women under 71 years of age with stageI, II, or III breast cancer were eligiblefor inclusion in a clinical study. 866 patientswith breast cancer entered the study, of whom463 had positive lymph nodes. Survival was analysed using Cox's proportional hazards model.Age at menarche, parity, age at menopause andfamily history were not consistently related to survival.Young age at first full-term pregnancy was relatedto decreased survival (adjusted relative risk (RR): 1.69,95% confidence intervals (95% CI): 1.04–2.68), but itcannot be excluded that this result was dueto chance alone. Use of oral contraceptives wasnot correlated with survival (RR: 1.10, 95% CI:0.80–1.51) nor was family history (RR: 0.93, 95%CI: 0.66–1.30). This study provided little support for the hypothesisthat risk factors for breast cancer are relatedto survival.
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  • 51
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    Breast cancer research and treatment 44 (1997), S. 75-82 
    ISSN: 1573-7217
    Keywords: breast cancer ; incidence ; Japan ; risk factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The incidence rate of breast cancer in Japanrose more than two-fold from 1959–60 to 1983–87.To assess to what extent this increase canbe explained by changes in the prevalence offour major risk factors of breast cancer (i.e.age at menarche, age at first birth, ageat menopause, and parity), we estimated the probabilityof developing breast cancer based on the jointdistribution and relative risks of these four riskfactors. The age-specific incidence rate during 1959–60 reportedby the Miyagi Prefectural Cancer Registry was usedto estimate the baseline hazard rate for womenwithout the four risk factors in the sameage group. Assuming that the baseline hazard rateis constant during all periods, we calculated theexpected incidence rates during the periods of 1959–60,1962–64, 1968–71, 1973–77, 1978–81, and 1983–87 for eachage group. Large discrepancies were noted between theobserved and expected incidence rates during 1983–87 inall age groups. The change in the jointdistribution of the four risk factors accounted forless than 40% of the increase observed from1959–60 to 1983–87, suggesting the effects of otherpowerful risk factors.
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  • 52
    ISSN: 1573-7217
    Keywords: Bcl-2 ; breast cancer ; Ki-S1 ; tamoxifen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Ki-S1, a marker of proliferation, and bcl-2, thegene product of which is an antagonist ofapoptosis, have been measured in 51 ER-positive primarybreast cancers before and during tamoxifen treatment andthen related to clinical response. Both markers weredetected in the majority of tumours before treatmentand, quantitatively, initial expression of Bcl-2 protein, butnot Ki-S1, was significantly related to the percentagereduction in tumour volume as assessed by ultrasound. Staining for both markers was lower in posttreatment samples than in those taken prior totreatments, but concordant decreases in staining indices wereseen in only 11 of the 51 tumours.The results demonstrate, using clinical material, that theresponse to tamoxifen may involve changes in proliferationand/or susceptibility to cell-death.
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  • 53
    ISSN: 1573-7217
    Keywords: breast cancer ; drug response ; induction chemotherapy ; p-glycoprotein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Expression and clinical relevance of p-glycoprotein (p-gp) were evaluated in 31 cases of locally advanced breast cancer and 9 cases involving inflammatory breast cancer after induction chemotherapy. The de novo p-gp expression rate was 26% and increased up to 58% (p = 0.03) with the FAC (5-fluorouracil, adriamycin, cyclophosphamide) regimen. Although more clinically complete responders were found in the secondary p-gp negative group (p = 0.02), this difference was not found in pathological tumor response. Moreover, as the grade of the secondary p-gp expression increased, the chemotherapeutic effect decreased, suggesting an inverse relationship between p-gp expression and drug effect (p = 0.04). When we subgrouped the patients into 4 groups using these two parameters, p-gp negative patients presenting with a high drug effect showed a low recurrence rate (p = 0.05) and marginal survival benefits (p = 0.09) as opposed to patients with a low drug effect. But in p-gp positive groups, the recurrence rate was the same between the two groups regardless of the drug effect. Thus, in the p-gp negative patient with a high drug effect, adjuvant chemotherapy with the same regimen as induction chemotherapy may induce more prognostically favorable results. Therefore, clinical application of the secondary p-gp detection can be used as an intermediate endpoint in evaluating drug response for an induction regimen.
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  • 54
    ISSN: 1573-7217
    Keywords: breast cancer ; ductal carcinoma in situ ; Gadolinium-DTPA ; galactography ; magnetic resonance imaging ; nipple discharge
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A new method of galactography using magnetic resonance imaging for a patient with nipple discharge is developed. The method is as follows; coronal T1-weight images are obtained after an injection of contrast medium of 1 mmol/L Gd-DTPA directly into the discharge duct, before and after rapid intravenous infusion of Gd-DTPA. A case of a 29-year-old woman with ductal carcinoma in situ with minimal invasion is reported, in which all portions of the entire discharge duct system is clearly shown as viewed from the surface and the surrounding area is enhanced with Gd-DTPA. The enhanced area is coincidental with the extent of the disease. This magnetic resonance galactography for patients with nipple discharge may be used to supplement conventional mammography and/or galactography especially for the evaluation of the extent of disease, although it is somewhat inferior to mammographic galactography in terms of differential diagnosis of ductal disease.
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  • 55
    ISSN: 1573-7217
    Keywords: apoptosis ; Bcl-2 ; breast cancer ; estrogen receptor ; intraductal cancer ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The expression of estrogen receptor (ER) and bcl-2(Bcl-2), an apoptosis protective oncogene, in normal andcancerous breast duct epithelia was immunohistochemically examined infresh frozen tumor tissues from 142 Japanese breastcancer patients. The clinico-pathological characteristics and the diseasefree survival of the patients were analyzed. Theexpression of both the proteins was also observedin intraductal components of breast cancer. Although lessthan 1% of normal duct epithelia expressed ER,Bcl-2 was diffusely expressed. The expression of boththese proteins in breast cancer significantly correlated witheach other. Their expression significantly correlated negatively withtumor size but not with lymph node status.The papillo-tubular sub-type of invasive ductal carcinoma expressedBcl-2 significantly more frequently than the solid-tubular sub-type.Patients with Bcl-2 expressing tumors survived without recurrencesignificantly more than those with tumors exhibiting reducedexpression. Papillary-cribriform type intraductal componentsexpressed both those proteins more often than the solid-comedo type.
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  • 56
    ISSN: 1573-7217
    Keywords: breast cancer ; endocrine therapy ; follow-up ; metastatic ; tamoxifen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To examine the outcomes of endocrine naive patients treated with tamoxifen as initial endocrine therapy for metastatic breast cancer. Data were obtained from the long-term follow-up of two previously published randomized trials. Patients and methods: All patients received tamoxifen 20 mg po in a single daily dose. Eligibility required patients to be age ≥ 18, performance status 0—3, and estrogen or progesterone receptor positive or unknown. Patients were ineligible if they had any prior endocrine therapy in either the adjuvant or metastatic setting. Results: 156 patients have been followed for a median of 8.3 years. Median age was 61 years, 83% were ≥ 50 years, 84% performance status of 0–1, 43% were both ER and PR positive, 33% had prior chemotherapy, 62% had a disease-free interval of 〉 2 years, and 59% had only one metastatic site. The complete (14%) and partial (6%) response rate for 147 evaluable patients was 20% (95% CI for CR + PR of 14–27%). Multivariate analysis revealed that improved response was related to soft tissue involvement and positive PR status. The majority of patients with soft tissue, nodal or lung metastases had responses noted within three months. Median time to disease progression was 6.7 months. Multivariate analysis revealed that older patients, those with one metastatic site and those with positive PR status had the longest time to progression. Median survival was 27.2 months. Better performance status, fewer metastatic sites and being PR positive were associated with significantly improved survival. Conclusion: The patient population in this series is not likely to be studied in future trials because of the wide use of tamoxifen in the adjuvant setting. In a small percentage of patients with metastatic breast cancer, tamoxifen therapy is associated with prolonged remission and survival. Pretreatment characteristics can help identify such patients.
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  • 57
    ISSN: 1573-7217
    Keywords: breast cancer ; body mass index ; parity ; physical activity ; pre-menopause ; post-menopause
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To further clarify risk factors for breast cancerin Japanese women, a self-administered questionnaire was completedby 157 cases with histologically confirmed breast cancerfrom 1989 to 1993 and by 369 ageand residential area matched controls in Gifu, Japan.Conditional logistic regression model was used to assessthe relations. Multivariate analyses showed that breast cancerrisk decreased with body mass index for premenopausalwomen (RR=0.45; 95% CI=0.22–0.92for BMI ≥ 23 vs. 〈 21 (kg/m2)),but the risk increased with body mass indexfor postmenopausal women (RR=1.98; 95% CI= 0.86–4.55 for BMI ≥ 24 vs. 〈21.5 (kg/m2)). The risk increased with a smallnumber of births in pre- and post-menopausal women(1.83; 1.11–2.99 and 6.06; 2.40–15.3 for 1–2 birthsand nulliparity, respectively, vs. ≥ 3 births). Ex-or current smoking increased the risk of breastcancer (2.31; 1.19–4.49). Reduced risk of premenopausal breastcancer was associated with high energy expenditure inphysical activity during teenage, although the trend wasnot statistically significant.
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  • 58
    ISSN: 1573-7217
    Keywords: basic fibroblast growth factor (bFGF) ; breast cancer ; cathepsin D ; MCF-7 ; mitogenic activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Mitogenic activity toward MCF-7 cells of two immunoreactive(high-molecular-weight form bFGF, HMW-bFGF; and 16-K bFGF, havingthe same molecular weight as recombinant bFGF) purifiedfrom pooled sera of breast cancer patients byheparin-affinity chromatography and gel filtration was investigated. Themitogenic activity of 16-K bFGF toward the cellswas equal to that of recombinant bFGF, whereasthe mitogenic effect of HMW-bFGF was weak. Mostof the mitogenic activity of these two bFGFswas neutralized by anti-bFGF antibody. Also, the mitogenicactivity of both HMW-bFGF and 16-K bFGF wasmarkedly enhanced by aspartyl protease (cathepsin D), whichis secreted in excess by breast cancer cellsand is responsible for the enzymatic degradation ofthe extracellular matrix (ECM). By an enzyme immunoassay,we detected cathepsin D-mediated release of recombinant bFGFpreviously bound to the ECM of MCF-7 cellsinto the conditioned medium, and also observed cathepsinD-mediated proteolysis of HMW-bFGF to release free 16-KbFGF. These results suggest that 16-K bFGF isthe bFGF molecule itself in the blood andthat HMW-bFGF is a circulating form of bFGFin blood whose mitogenic activity is regulated bycathepsin D.
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  • 59
    ISSN: 1573-7217
    Keywords: breast cancer ; immunohistochemistry ; HSP70 ; PCNA ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A series of 80 female patients undergoing surgeryfor primary breast ductal infiltrating carcinoma not otherwisespecified (NOS) was immunohistochemically studied in order toverify any relationships between Proliferating Cell Nulear Antigen(PCNA) immunostaining, Heat Shock Protein 70 (HSP70) immunoreactivity,and several clinicopathological predictors.Positive PCNA scores (〉 20% of strongly immunopositivemalignant nuclei) were observed in neoplastic cells' nucleiin 13 tumors (16.25%) and were intimately associatedwith axillary nodal involvement (p=0.0131), relativelyhigh tumor grades (p=0.0016), increased tumorsize (p=0.0312), and low or negativelevels of estrogen receptors (p=0.0323). HSP70positive immunoexpression in malignant cells' cytoplasm (percentage ofHSP70 immunoreactive cells 〉 10%) was detected in33 samples (41.25%). It correlated significantly with presenceof axillary lymph nodal metastases (p=0.0033)and rather poor tumor differentiation (p=0.0014),whereas an association of borderline statistical significance emergedbetween HSP70 immunoreactivity and high progesterone receptor status(p=0.0637).PCNA positive immunostaining demonstrates the tumors' proliferative fractionand might be used as an indicator ofincreased malignant potential in breast cancer since itwas associated with four adverse prognosticators. HSP70 immunodetectionis a probable marker of the biological stressexperienced by breast cancer cells, since it wasrelated to relatively high tumor grades. Since bothproteins may potentially predict disease outcome, their prognosticsignificance must be validated by direct relation tosurvival. A multivariate statistical analysis including the variableswith which both proteins were associated will revealany possible independent prognostic value of PCNA andHSP70 immunostaining in local, ductal invasive breast cancerNOS.
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  • 60
    ISSN: 1573-7217
    Keywords: midkine ; breast cancer ; growth factor ; truncated form ; RT-PCR ; immunohistochemical analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The expression of midkine (MK), a growth/differentiation factor,was assessed in 34 surgically resected specimens ofprimary breast cancer or mastopathy. Using reverse transcriptase-polymerasechain reaction (RT-PCR) analysis, all of the non-cancerousand cancerous tissues were found to express MKexcept for one breast cancer specimen. Northern blotanalysis revealed that MK mRNA was also expressedin the normal breast tissues examined. Immunohistochemical analysisof the MK protein was performed on alimited number of the specimens, showing that somecancerous tissues were immunoreactive with anti-MK antibodies. Furthermore,using RT-PCR analysis, expression of not only thewild-type but also a truncated form of MK,which was recently found in various human tumorcell lines, was detected in 6 of 26cancerous tissues but not in non-cancerous tissues.
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  • 61
    ISSN: 1573-7217
    Keywords: breast cancer ; breast self-examination ; cohort study ; mortality
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The benefits of breast self-examination (BSE) for reducingmortality from breast cancer are uncertain. We conductedan analysis of the relationship between self-reported practicingof BSE and mortality from breast cancer over13 years in a cohort of over 548,000women. The report of practicing BSE was unrelatedto breast cancer mortality. There was a smallbeneficial effect in those women who were thethinnest, but this effect was small and notstatistically significant. BSE was otherwise equally ineffective insubgroups defined by obesity level and family historyof breast cancer. We conclude that BSE, aspracticed by American women in 1959, did notreduce the risk of mortality from breast cancer.
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  • 62
    ISSN: 1573-7217
    Keywords: breast cancer ; uPA ; PAI-1 ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cancer cell invasion is accomplished by the concertedaction of several extracellular proteolytic enzyme systems, oneof which is the urokinase plasminogen activation system.The different components of this system, e.g. urokinaseplasminogen activator (uPA), its receptor uPAR, as wellas its main inhibitor plasminogen activator inhibitor type1 (PAI-1) have all been shown to haveprognostic value in breast cancer, i.e. high tumorlevels are associated with a poor prognosis.In orderto further substantiate the prognostic value of uPAand PAI-1, we have tested the cutpoints (medianvalues and optimized cutpoints) from our first study(Cancer Res 53: 2513–2521, 1993) in an independentgroup of breast cancer patients. Breast cancer cytosolsfrom 100 premenopausal and 150 post-menopausal node positivepatients were included. The median observation time was80 months (range 49–145). Univariate analysis showed thathigh PAI-1 levels (above the median PAI-1 value)were significantly associated with short recurrence-free survival (RR:1.65; 95% CI: 1.04–2.63; P=0.03) andshort overall survival (RR: 2.46; 95% CI: 1.52–3.96;P=0.0001) in postmenopausal patients. Postmenopausal patientswith high uPA levels (above the median uPAvalue) had a significantly shorter recurrence-free survival (RR:2.04; 95% CI: 1.17–3.56; P=0.01) andoverall survival (RR: 2.07; 95% CI: 1.16–3.70; P= 0.01) than patients with low uPA values.Nearly identical results were obtained when using theoptimized PAI-1 or uPA value.In a Cox multivariateanalysis which included other established prognostic factors, highPAI-1 was found to be an independent prognosticvariable predicting short overall survival with a relativerisk of 2.27 in postmenopausal women, and highuPA was found to be an independent prognosticvariable predicting short recurrence-free survival with a relativerisk of 1.86 in postmenopausal women. The presentstudy indicates that uPA and PAI-1 are independentand significant prognostic variables in subsets of breastcancer patients.
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  • 63
    ISSN: 1573-7217
    Keywords: breast cancer ; cell lines ; characterisation ; chemosensitivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Human breast cancer cell lines are required asmodels for use in the understanding of breastcarcinoma, and for improving the ability of cellscreens to detect appropriate anti-cancer agents. Four humanbreast cancer cell lines (MT-1, MaTu, MT-3 andMC4000) were established from human tumour xenografts grownin nude mice. All the lines were shownto be of human origin by karyotype analysis,were epithelial in morphology by both light andelectron microscopy, were positive for cytokeratin 18, andwere free from mycoplasma, bacterial, yeast and fungalcontamination. All of the new lines were shownto be ER and PgR negative, while usingthe same procedures (i.e. radioligand binding and immunohistochemicalstaining) the positive control cell line MCF-7 wasshown to be positive. MaTu had been previouslyreported as ER and PgR positive in vivoand it may be that this characteristic hadbeen lost due to in vitro selection pressures.The growth rates of all the new breastcancer cell lines were similar and within thelimits required for incorporation into a panel forscreening anticancer drugs by a microtetrazolium based, colorimetricgrowth inhibition assay. Three of the lines (MT-1,MaTu and MC4000) were also able to growinto macroscopic colonies for use in a non-agarclonogenic assay. In addition, both MT-1 and MaTuformed spheroids and were clonogenic in soft-agar. Thenew lines demonstrated a wide range of sensitivitiesto anticancer agents commonly used in the treatmentof breast cancer, and together with their correspondingxenografts are providing additional systems for the evaluationof new compounds.
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  • 64
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    Breast cancer research and treatment 43 (1997), S. 123-128 
    ISSN: 1573-7217
    Keywords: breast cancer ; risk, height ; measurement error
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Inter- and intra-national epidemiological studies point to anassociation between socio-economic status and breast cancer risk.Although there is no direct evidence, the mostfavoured reason for this relationship is nutritional. Anenhanced dietary status, especially during childhood, would bereflected in adult body build. It is, therefore,surprising that there is uncertainty in the literatureconcerning the association between height and breast cancerrisk. In reviewing the publications on this topic itbecame apparent that case-control studies which found noassociation between height and risk tended to useself-reported height. In contrast reports claiming a significant,and positive, correlation tended to use heights whichwere measured by the investigators. In a prospective study we found in a cohort of 2731 ostensiblynormal women that, although there was a highlysignificant linear correlation between self-reported and measured height,the shortest women over-estimated their height whilst thetallest volunteers under-estimated theirs. The significance of cruderelative risk and height in this cohort wasmarkedly attenuated when self-reported height was used comparedto measured height. Such a systematic error couldhave a profound effect on the conclusions ofstudies in this field which relied on self-reportingand could explain the conflicting reports in theliterature.
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  • 65
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    Breast cancer research and treatment 43 (1997), S. 99-103 
    ISSN: 1573-7217
    Keywords: WAF1/CIP1 protein ; p53 protein ; breast cancer ; immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract WAF1/CIP1 is a cyclin-dependent kinase inhibitor which isdirectly induced by p53 and negatively controls cellproliferation. To test the hypothesis that increased levelsof WAF1 would be associated with a lowerS-phase fraction and better prognosis, WAF1 protein wasassessed by immunohistochemistry (IHC) in 115 node-negative humanbreast tumors, and results were correlated with establishedprognostic factors and clinical outcome. Nuclear staining wasobserved in malignant cells in 43% of tumors.In most (90%) of the positive tumors, theproportion of cells staining for WAF1 was low(〈 10%). WAF1 was not detected in thecytoplasm, or in non-malignant epithelium. Contrary to expectations,the accumulation of p53 protein, a surrogate markerof p53 inactivation, was weakly but positively associatedwith WAF1 expression (p=0.05). Surprisingly, therewas no significant correlation with S-phase fraction, ERor PgR status, tumor size, age, ploidy, nucleargrade, or survival. Conclusion: WAF1 expression is found inthe nuclei of a small fraction of cellsin human breast tumors. WAF1 status is notsignificantly associated with cell proliferation, other established prognosticfactors, or clinical outcome.
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  • 66
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    Breast cancer research and treatment 43 (1997), S. 165-173 
    ISSN: 1573-7217
    Keywords: breast cancer ; CD44 ; estrogen receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To understand the relationship between CD44 gene expressionand an established variable associated with aggressive behaviourin human breast cancer, we have studied apanel of 6 breast cell lines and 40breast tumors selected primarily on the basis ofestrogen receptor (ER) status. CD44s (standard form) mRNAwas assessed by semi-quantitative RT-PCR, and CD44 variantsincorporating exon v7 or v10 were studied byRT-PCR and Southern blot. While CD44 expression wasnot influenced by estrogen in ER+ve MCF-7 cells,CD44s expression was slightly higher (up to 2fold) in ER−ve cells but there was amarked decrease in the range of CD44 variantsincorporating exons v7 or v10. In microdissected tumors,the levels of CD44s showed no correlation withER status but the pattern of expression oflarger forms of CD44 incorporating variant exons v7and v10 was significantly different (p=0.005and p=0.015, respectively) between ER+ve andER−ve tumors, reflecting the pattern seen in thecell lines. These findings suggest that the profileof CD44 expression in breast cancer may reflectcellular differentiation as indicated by the ER phenotype.The influence of these differences in CD44 expressionon the increased metastatic potential of ER negativebreast cancer remains to be determined.
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  • 67
    ISSN: 1573-7217
    Keywords: breast cancer ; cell proliferation ; dietary fat ; Ki-67 ; mammographic densities ; PCNA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Increased dietary fat intake and rate of breastepithelial cell proliferation have each been associated withthe development of breast cancer. The goal ofthis study was to measure the effect ofa low fat, high carbohydrate diet on therate of breast epithelial cell proliferation in womenat high risk for breast cancer. Women wererecruited from the intervention and control groups ofa randomized low fat dietary intervention trial, breastepithelial cells were obtained by fine needle aspiration,and cell proliferation was assessed in these samplesusing immunofluorescent detection of Ki-67 and PCNA. Theeffects of needle size and study group oncell yield and cytologic features of the cellswere also examined. Fifty three women (20 inthe intervention group and 33 in the controlgroup) underwent the biopsy procedure. Slides from 38subjects were stained for Ki-67 and from 14subjects for PCNA. No cell proliferation (fluorescence) wasdetected for either Ki-67 or PCNA in anyof the slides. Epithelial cell yield and numberof stromal fragments were greater with a largerneedle size. Numbers of stromal fragments and bipolarnaked nuclei were greater in the low fatas compared to the control group but nodifferences in epithelial cell yield were observed betweenthe two groups. This study confirms that fineneedle aspiration biopsy is a feasible method ofobtaining epithelial cells from women without discrete breastmasses, but suggests that cell proliferation cannot beassessed using Ki-67 and PCNA in such samples.
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  • 68
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    Breast cancer research and treatment 43 (1997), S. 259-276 
    ISSN: 1573-7217
    Keywords: breast cancer ; treatment guidelines ; systemic therapy ; prognostic factors ; dose intensification ; chemotherapy ; radiation therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Optimal treatment of early stage breast cancer remainsan active area of study. An expert multidisciplinarycommittee reviewed clinical data on systemic therapy forearly stage, stage I and II breast cancer.Guidelines for treatment were developed for Texas Oncology,P.A., the largest private practice group of oncologistsin the United States. This group of physicianstreats approximately 5000 new breast cancer patients eachyear and has a major impact on oncologycare in the state of Texas. These guidelines identify prognostic factors which help thepractitioner in choosing treatment for patients. Subsets ofpatients are identified for whom no systemic therapyis warrented. Standard chemotherapy and hormonal therapy regimensare outlined for patients with early stage diseaseat increased risk for relapse. Dose intensification forhigh risk stage II patients is reviewed. Timingof therapy and the sequencing of chemotherapy andradiation therapy is addressed. Strategies for the follow-upof patients with a history of breast cancerare outlined.
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  • 69
    ISSN: 1573-7217
    Keywords: breast cancer ; fine needle aspiration ; immunocytochemistry ; flow cytometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study was undertaken to evaluate our abilityto detect multiple molecular markers of prognosis andresponse to treatment in fine needle aspirates (FNA)from patients with primary breast carcinomas. 147 patientswith operable primary breast carcinomas who had beenrecruited to a randomized trial of primary medicaltherapy (PMT) versus adjuvant chemoendocrine therapy were analysed.FNAs were taken prior to therapy and fromthis multiple slides were produced using cytospin cytocentrifugationand stored at − 80 °C for subsequentimmunocytochemical analysis (ICA). ICA was performed for oestrogenreceptor (ER), progesterone receptor (PgR), p53, Ki67, andBcl-2. Part of the aspirate was snap frozenand used for flow cytometric analysis of ploidyand S-phase fraction (SPF). In a subgroup of50 patients who had surgery prior to systemictherapy, as well as FNAs, sections were alsotaken from paraffin-embedded blocks and stained by ICAfor ER, PgR and p53 for validation. Inthese patients ER was additionally measured by enzymeimmunoassay (EIA) from frozen tissue taken at surgery.ER, PgR, p53, Bcl-2, and Ki67 were successfullydetected by ICA while ploidy and SPF weresuccessfully measured by flow cytometry from FNA material.The percentage positive values obtained were reasonable andas follows: 74% for ER, 70% for PgR,36% for p53, 80% for Bcl-2. 68% oftumours were aneuploid and 32% diploid. Significant relationshipsbetween these measurements were observed in accordance withexpectations. The concordance for ER, PgR, and p53from FNA when compared to ICA of matchinghistological sections was 91.5%, 75.5%, and 75% respectively.For ER the concordance between measurement by ICAof cytological and histological samples and by EIAof frozen tissue was 82.5% and 84% respectively.These results indicate that multiple molecular markers canbe adequately tested on cytological preparations from primarybreast tumours. These markers can be used todetermine prognosis and predict response to PMT.
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  • 70
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    Breast cancer research and treatment 44 (1997), S. 23-38 
    ISSN: 1573-7217
    Keywords: antiestrogens ; tamoxifen ; estrogen receptor ; antiestrogen resistance ; breast cancer ; hormone sensitivity ; endocrine therapy ; resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Antiestrogens have proven to be highly effective in the treatment of hormone-responsive breast cancer. However, resistance to antiestrogen therapy often develops. In addition, although tamoxifen-like antiestrogens are largely inhibitory and function as estrogen antagonists in breast cancer cells, they also have some estrogen-like activity in other cells of the body. Thus, recent efforts are being directed toward the development of even more tissue-selective antiestrogens, i.e. compounds that are antiestrogenic on breast and uterus while maintaining the beneficial estrogen-like actions on bone and the cardiovascular system. Efforts are also being directed toward understanding ligand structure-estrogen receptor (ER) activity relationships and characterizing the molecular changes that underlie alterations in parallel signal transduction pathways that impact on the ER. Recent findings show that antiestrogens, which are known to exert most of their effects through the ER of breast cancer cells, contact a different set of amino acids in the hormone binding domain of the ER than those contacted by estrogen, and evoke a different receptor conformation that results in reduced or no transcriptional activity on most genes. Resistance to antiestrogen therapy may develop due to changes at the level of the ER itself, and at pre- and post-receptor points in the estrogen receptor-response pathway. Resistance could arise in at least four ways: (1) ER loss or mutation; (2) Post-receptor alterations including changes in cAMP and phosphorylation pathways, or changes in coregulator and transcription factor interactions that affect the transcriptional activity of the ER; (3) Changes in growth factor production/sensitivity or paracrine cell-cell interactions; or (4) Pharmacological changes in the antiestrogen itself, including altered uptake and retention or metabolism of the antiestrogen. Model cell systems have been developed to study changes that accompany and define the antiestrogen resistant versus sensitive breast cancer phenotype. This information should lead to the development of antiestrogens with optimized tissue selectivity and agents to which resistance may develop more slowly. In addition, antiestrogens which work through somewhat different mechanisms of interaction with the ER should prove useful in treatment of some breast cancers that become resistant to a different category of antiestrogens.
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  • 71
    ISSN: 1573-7217
    Keywords: estrogen receptor ; mutation ; breast cancer ; gene expression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A novel ER-like mRNA containing a 69 nucleotideinsertion precisely between exon 5 and 6 sequenceswas previously identified in human breast cancer biopsysamples. Data are presented which suggest that the69 nucleotide sequence is normally present in intron5 of the human estrogen receptor gene. Theregion corresponding to and surrounding this 69 nucleotidesequence was cloned and the nucleotide sequence determined.Cloning and sequencing of the corresponding region ingenomic DNA isolated from a breast tumor expressingthe 69 nucleotide inserted ER mRNA, revealed anA→G point mutation immediately 3′ to the69 nucleotide sequence. This point mutation resulted inthe generation of a consensus splice donor site.A consensus splice acceptor site sequence is normallypresent immediately 5′ to the 69 nucleotide sequence.These data are consistent with the 69 nucleotidesequence being recognized as an exon by thesplicing machinery, and resulting in processing of amature ER mRNA containing the 69 nucleotide insert.
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  • 72
    ISSN: 1573-7217
    Keywords: breast cancer ; tamoxifen ; weight gain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There is a perception that tamoxifen causes weightgain in breast cancer patients. The purpose ofthis research study was to determine if weightgain is associated with tamoxifen therapy and toobserve the impact of weight gain on recurrenceand survival. Prognostic indicators, changes in weight, anddisease status from diagnosis to the end oftreatment were studied in 200 consecutive Stage Iand II breast cancer patients, not receiving systemicchemotherapy, admitted from 1986 to the present, withobservation periods ranging from 3–5 years. A meanweight gain of 1.2 Kgs was seen inall patients; however, weight gain was not significantlydifferent for those receiving tamoxifen vs. those notreceiving tamoxifen, (P=0.66, CI 95% forthe difference –1.8 Kgs to +1.2 Kgs). Weightgain during treatment with tamoxifen was not correlatedwith treatment duration or with recurrence or survival.Age at diagnosis was positively correlated to weightgain in all groups. Our data failed toshow that tamoxifen is associated with weight gain.The moderate weight gain observed in this patientpopulation is comparable to the general aging disease-freepopulation and may not be treatment-related. These findingsmay help to alleviate some concerns of bothphysicians and patients when tamoxifen is the drugof choice for adjuvant therapy.
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  • 73
    ISSN: 1573-7217
    Keywords: biological features ; breast cancer ; primary chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. To evaluate the changes in the biological features of breast cancer cells induced by primary chemotherapy (PCT) and their possible relationship with the response to therapy, we performed an extensive immunohistochemical study before and after PCT. Patients and methods. PCT was administered to 29 women with breast cancer. On specimens obtained by tru-cut and post-chemotherapy surgery we analyzed the following parameters: histology, histologic grade, apoptotic index, hormone receptor levels, Ki67, PCNA, EGFr, bcl-2, p53, p170. The significance of the changes induced by PCT and their correlations with the type of response were evaluated. Results. Twelve patients achieved a partial response with PCT. No baseline biological parameter correlated with the type of response. After PCT we observed a significant increase in the apoptotic index (p = 0.000), PCNA (p=0.036), EGFr (p = 0.005), and p170 expression (p=0.001), regardless of the type of chemotherapy administered (anthracyclines, 25 cases, or CMF, 4 cases). Responder patients displayed a significant decrease in ER levels (p = 0.015), whereas in non responders there was an increase in PCNA (p=0.008) and EGFr expression (p=0.002). The apoptotic index and p170 expression rose after PCT regardless of the type of response. Conclusions. PCT induced significant variations in the phenotype of breast cancer cells. These changes might reflect the selection of new neoplastic clones with different biological properties and so could facilitate the choice of appropriate chemotherapy agents.
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  • 74
    ISSN: 1573-7217
    Keywords: breast cancer ; classification schemes ; measure of separation ; node negative ; recurrence-free survival ; validation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Several prognostic classification schemes in node negative breastcancer are proposed, but only the Nottingham PrognosticIndex (NPI) seems to be sufficiently validated. Validation,which is a prerequisite for a sensible assessment,is not published for two recent proposals accordingto Glick et al. [1] and Rubens [2].The German Breast Cancer Study Group (GBSG) entered662 eligible patients in a prospective observational study.603 of them had complete data for seven’standard‘ prognostic factors and median follow-up is about5 years. As there is no accepted andinformative measure of separation for classification schemes presentlyavailable, we propose a new one and useit additionally to the well known logrank-test andKaplan-Meier estimates to investigate the predictive power ofthe three schemes. Significant differences in survival andrecurrence-free survival could be established for the NPIsubgroups but not for others where even theordering of the groups was different. With theCox model and the classification and regression treeapproach we develop two new proposals for thedifferentiation of subgroups of node negative patients. Asin the NPI, tumor size and grade arethe most important factors, but with a differentweighting scheme. Young age (≤ 40 years) andvery high estrogen receptor values (〉 300 fmol)in a small subgroup of patients were associatedwith worse prognosis. The new proposals showed abetter degree of separation, which demonstrates that animprovement seems possible using standard factors. Because themeasures of separation give an overoptimistic impression forthe new proposals, a validation with other studiesis necessary before a general recommendation can begiven.
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  • 75
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    Breast cancer research and treatment 42 (1997), S. 113-120 
    ISSN: 1573-7217
    Keywords: angiogenesis ; breast cancer ; lymphatics ; oncogenes ; prognosis ; vascularity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Clearance of large molecules from the interstitialspace is an important function of lymphatics andis affected by local pathologic changes.Objective: To determine if the clearance rate ofinterstitially injected albumin is correlated to tumour characteristicsand outcome in women with invasive breast cancer.Method: In a consecutive series of women comingto biopsy for suspected breast cancer, technetium-tagged albuminwas injected into the tissue adjacent to thepalpable mass. The isotope disappearance rate was measuredover two hours. Also assessed were the maximumvessel density (MVD – using Factor VIII polyclonalantisera), the proliferation rate (using Ki-67 antisera), nodestatus, tumour size, histologic and nuclear grade, mitoticrate, and p53 and c-erbB-2 oncoproteins. All patientswere followed until relapse and for a minimumof 10 years.Results: In multivariate analysis, an association between relapse-freesurvival and isotope clearance rate was suggested (p= 0.024). The best outcome was seen inpatients with the least isotope clearance. Node status,size, histologic and nuclear grade, and mitotic ratecorrelated with survival. MVD did not correlate withsurvival and was inversely related to the isotopeclearance rate. Tumour proliferation rate, and the c-erbB-2and p53 oncoproteins did not relate to outcome.Conclusion: The role of lymphatics in breast canceris difficult to study. Measurement of interstitial clearancemay be a useful technique and could bea prognostic factor.
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  • 76
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    Breast cancer research and treatment 42 (1997), S. 207-213 
    ISSN: 1573-7217
    Keywords: breast cancer ; matrix metalloproteases ; stroma ; tumor angiogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Several proteinases, implicated in tumor invasion, are expressed in fibroblastic cells surrounding neoplastic cells, and are believed to be induced by paracrine stimulation. Such stimulation, by the local release of angiogenic factors, is also responsible for the induction of new capillary blood vessels, a crucial aspect of tumor growth and metastasis. We have here compared the expression of a matrix metalloproteinase, stromelysin-3 (ST3), with the distribution of tumor microvessels in invasive breast carcinomas. The highest level of ST3 mRNA in each tumor was recorded and compared to the highest microvessel density. No correlation between these two parameters was observed by analysis of 63 tumors. Detailed examination of 19 individual tumors did not reveal any correlation between the distribution of ST3 mRNA and microvessels. In the material studied here, ST3 expression was observed to correlate with long-term survival of the patients, whereas microvessel density did not correlate.
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  • 77
    ISSN: 1573-7217
    Keywords: breast cancer ; membrane receptor ; SBP ; SHBG ; thymidine kinase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the last years, an increasing amount of studies described a membrane receptor for the Sex Steroid Binding Protein (SBP) on several androgen-estrogen dependent tissues. One of the suggested biological roles of the interaction between SBP and its receptor seems to be a negative control of the E2 induced proliferation of human breast cancer cells through the cAMP pathway. In the present work, SBP membrane receptor was evaluated on human breast cancer specimens with a radio-binding assay. Each tissue sample was also evaluated for ER and PGR status. Cytosol Thymidine Kinase levels were measured in tissue samples in order to evaluate cell proliferation rate. SBP binding to membranes of ER +/PGR + samples was time and temperature dependent, specific and at high affinity. In addition, SBP recognized on breast cancer membranes two sites at different affinity, as previously described for other human tissues and cultured cells. Membrane SBP-R was detected in a significantly higher number of samples positive for both ER and PGR than in negative samples. SBP-R positive samples showed a significantly lower proliferation rate than SBP-R negative samples as demonstrated by TK activity. The present study contains evidences for the existence of a specific membrane receptor for SBP in breast cancer sample membranes and the presence of SBP-R seems to be strictly related to a lower proliferation rate of the sample.
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  • 78
    ISSN: 1573-7217
    Keywords: breast cancer ; c-erbB-2 ; chemotherapy ; oncogene ; prognosis ; survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This retrospective case control study investigated the therametricvalue of the circulating c-erbB-2 gene product (Her-2,NEU) as (1) an eligibility criterion for highdoses of chemotherapy and (2) response to standardadjuvant chemotherapy in node-positive breast cancer patients. Preoperativec-erbB-2 levels were measured in 211 locally advanced(〉 3 nodes positive), pre- and perimenopausal breastcancer patients to determine if circulating levels ofthe gene product can assist in the determinationof appropriate therapeutic options.152 of 211 breast cancer patients received post-operativelya combination chemotherapy including the anthracycline analog mitoxantrone,while 59 patients were treated with conventional CMFtherapy. Using 120 fmol/ml as a cut-off level,elevated c-erbB-2 values were found in 26 (12.3%)patients with locally advanced breast cancer. In univariateanalysis significant survival differences were detected when c-erbB-2‘positive’ patients were compared with c-erbB-2 ‘negative’ patients.However, no significant survival differences were detected, whenc-erbB-2 ‘positive’ patients were compared according to regimenof adjuvant treatment.In multivariate analysis c-erbB-2 was an independent prognosticfactor for predicting disease-free survival, but not foroverall survival. High levels of c-erbB-2 were associatedwith low estrogen and progesterone receptor concentrations ofthe tumor cytosol. There was no correlation betweenelevated c-erbB-2 values and age, tumor size ordegree of nodal involvement. c-erbB-2 was a betterpredictor of risk of recurrence than extent ofnodal involvement or hormone receptor status.
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  • 79
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    Breast cancer research and treatment 46 (1997), S. 143-159 
    ISSN: 1573-7217
    Keywords: estrogens ; depression ; aggression ; cognitive functions ; alcohol intake ; stress ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The possible role of personality patterns and psychosocial factors in breast cancer has been studied extensively, through both human and animal experiments. The data are conflicting, and the conclusions controversial. This review will serve two purposes. First, we present evidence that behavioral patterns most commonly linked to breast cancer risk are at least partly regulated by estrogens. This section will suggest that some estrogen-regulated behaviors may be markers of increased breast cancer risk. Second, we will briefly review recent findings in animals connecting psychosocial factors to cancer. We also will address the plausible biological mechanisms. The literature suggests that estrogens, particularly when exposure occurs during the critical developmental periods, such as in utero, puberty, pregnancy, and menopause, influence affective behaviors and increase breast cancer risk. The affective behaviors include depression, aggression, and alcohol intake. Thus, psychosocial and personality factors do not necessarily have a direct impact on breast cancer risk; instead, estrogens have a dual effect on behavior and on the breast.
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  • 80
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    Breast cancer research and treatment 46 (1997), S. 117-133 
    ISSN: 1573-7217
    Keywords: animal models ; breast cancer ; cell lines ; DMBA ; NMU ; AIN76 ; AIN93
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This is the second Special Issue addressing the diversity and use of animal models of breast cancer. The previous issue (Breast Cancer Res Treat 39:1-135, 1996), dealt with a variety of topics such as the characteristics of chemically- and virally-induced rodent models, immunobiologies of immunedeficient mice, transgenic mouse models, and models of metastasis. In the first part of this second Special Issue, the articles address animal models for studying life-style factors, including psychosocial, exercise, and nutritional research in breast cancer. In the second section, there is emphasis on the controversial area of dietary fat, with other authors addressing caloric restriction and dietary isoflavonoids, retinoids, and monoterpenes in the third part. In the final section, a series of authors provide suggestions for approaching various issues involving experimental design, including nutritional studies, drug screening models, statistical considerations, quantitation of tumor growth kinetics, and animal husbandry. These articles, and some additional issues raised during the previous Special Issue, are briefly discussed in this overview. They include a further evaluation of the relative merits of 7,12-dimethylbenz(a)anthracene and N-nitroso-N-methylurea as carcinogens, and of the use of the AIN76 and AIN93 semipurified diets in studies of mammary carcinogenesis.
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  • 81
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    Breast cancer research and treatment 45 (1997), S. 149-158 
    ISSN: 1573-7217
    Keywords: breast cancer ; c-neu/erbB2 oncogene ; diet ; dietary fiber ; transgenic mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Breast cancer is one of the most commoncancers in women. The laboratory rat treated withstrong carcinogen is the most commonly used animalmodel for study of breast cancer. Transgenic mouselines with homologues of human breast cancer oncogeneshave been developed. The transgenic mouse line TG.NKwith c-neu, the human breast cancer oncogene homologueof erbB2, was evaluated to determine its suitabilityfor study of intervention strategies to delay/prevent thedevelopment of breast cancer. There were no palpablemammary tumor masses up to 22-weeks of age,and almost all mice fed a purified dietdeveloped palpable mammary tumors by 28-weeks of age.Nonpurified diets decreased the incidence and multiplicity, anddelayed the development of mammary tumors as comparedto a purified diet. Increasing the fiber contentof nonpurified diet decreased the tumor incidence further.There is approximately a 19-week interval between weaningand development of palpable mammary masses to evaluateintervention strategies to delay or prevent the developmentof mammary cancer in the TG.NK mouse model.Fiber from nonpurified cereal ingredients appears to behighly beneficial in delaying the development of mammarycancer in TG.NK mice, and this observation isin agreement with human epidemiological findings. Therefore, theTG.NK transgenic mouse with oncogene c-neu (erbB2), appearsto be a useful animal model for evaluationof dietary intervention strategies.
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  • 82
    ISSN: 1573-7217
    Keywords: breast cancer ; mass mammography ; screening ; mortality
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Results from several randomised mammography screening trials haveshown that it is possible to reduce mortalityin breast cancer by mammographic screening at leastfor women above 50 years of age. Thepurpose of this article is to present dataon mortality in breast cancer in study andcontrol groups of the Stockholm trial after 11years of followup, to analyse which age groupbenefits most from screening. In March 1981, 40,318women in Stockholm, aged 40 through 64 years,entered a randomized trial of breast cancer screeningby single view mammography alone, versus no interventionin a control group of 20 000 women.Two screening rounds were performed and the attendancerate was over 80% in the two rounds.During 1986 the control group was invited onceto screening. Totally 428 and 217 cases ofbreast cancer were diagnosed in the study andcontrol groups respectively. After a mean follow-up of11.4 years a nonsignificant mortality reduction of 26%was observed for the whole study group, witha relative risk (RR) of death in breastcancer of 0.74 (CI(confidence interval)=0.5–1.1). Forwomen aged 50–64 years a significant 38% mortalityreduction was observed with a RR of 0.62(CI=0.38–1.0). For women aged 40–49 yearsno effect on mortality was found, with aRR of death in breast cancer of 1.08(CI=0.54–2.17). The breakpoint for benefit inthis study seemed to be at 50 yearsof age when 5-year age groups were analysed,but this tendency is uncertain because of thelow statistical power in the analysis of theyounger age groups. Long screening intervals, the useof single-view mammography, and the fact that morethan 50% of the women in age group40–49 years were still below 50 years ofage when the study was closed, were allfacts that could have influenced the results inage group 40–49 years. Larger studies are neededto answer the question whether mammographic screening canbe successful in younger age groups.
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  • 83
    ISSN: 1573-7209
    Keywords: Angiogenesis ; breast cancer ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Experimental and clinical studies have shown that human breast cancer is an angiogenesis-dependent neoplasm. In fact, several authors have demonstrated that the determination in primary tumors of the degree of vascularization (microvessel counts) as well as of some angiogenic peptides is of prognostic value. However, which are the most important mediators of angiogenesis and their relationship with other relevant biological markers needs further investigation. In the series of 260 women with node-negative breast cancer (NNBC) on which we previously assessed vascular endothelial growth factor (VEGF), we have now also determined thymidine phosphorylase (TP) protein as well as p53 protein and Cathepsin-D cytosolic levels using immunometric methods. The median concentrations of TP, p53 and Cathepsin-D were 105.4U/mg (range 1.2–843.1), 0.22 ng/mg (range 0.0–41.65) and 33.80nmol/mg (range 4.20–216.0), respectively. We found that TP concentrations were associated with Cathepsin-D and p53, but not with VEGF. VEGF (p〈0.0001) and p53 (p = 0.03 and p = 0.012, respectively) were found to be statistically significant prognostic variables for both relapse-free survival (RFS) and overall survival in univariate analysis. Conversely, TP and Cathepsin-D levels did not correlate with prognosis. In multivariate analysis for RFS, VEGF levels (p〈0.0001), TP levels (p = 0.050) and their first-order interaction terms (p = 0.027) were statistically significant prognostic indicators. Cathepsin-D and p53 protein levels did not retain significance in the model inclusive of all the above variables. The predictive capability of the complete model was satisfactory (Harrell c statistic = 0.72). Moreover, these results suggest a possible potentiation of the capability of predicting the likelihood of recurrence by the co-determination of TP and VEGF. The probability of recurrence was particularly high in the patients with primary tumors characterized by elevated levels of both angiogenic factors. This is the first study showing in vivo that two different angiogenic peptides concur in the progression of human breast cancer. The biology and possible therapeutic implications of this observation are discussed.
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  • 84
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    Breast cancer research and treatment 42 (1997), S. 43-55 
    ISSN: 1573-7217
    Keywords: diet ; body size ; breast cancer ; prognostic factors ; survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Nutritional factors have been suggested to play an important role in the prognosis of breast cancer through their effect on tumor characteristics. This study evaluated four tumor characteristics and prognosis in relation to premorbid diet and body size. From a cohort of 89,835 women in the National Breast Screening Study (NBSS) in Canada, data on 676 incident cases of invasive carcinoma of breast, on whom we had dietary information, were used. A high energy intake lowered the likelihood of being ER positive and PR positive but after adjusting for ER status, was still associated with a higher risk of dying of breast cancer. Total fat and various types of fats were associated with a greater likelihood that a woman would be ER and PR positive, however the likelihood of dying from breast cancer was higher with higher fat consumption. There was no significant effect of higher intakes of beta carotene or vitamin C on ER status, nodal status or tumor size, but a significantly lower risk of dying from breast cancer was observed. Higher intake of carbohydrates and calcium was associated with a lowered frequency of ER and PR positive status but also with a lower risk of dying. Of the five indicators of body size studied, higher triceps skinfold thickness was associated with a slightly lower chance of being ER positive, PR positive, and node negative, and a significantly higher likelihood of dying. It appears that while there are significant associations between some of the diet and body size variables and tumor characteristics, the effect of most nutritional factors on prognosis in breast cancer may not be mediated via their effect on tumor characteristics.
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  • 85
    ISSN: 1573-7217
    Keywords: bone marrow ; breast cancer ; micrometastases ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The presence in bone marrow of cells which react with monoclonal antibodies against tumor-associated antigens has been proposed over the last few years as a new prognostic factor in breast cancer patients. Patients and methods: Bone marrow aspirates were obtained from 109 stage I and II breast cancer patients during or 2–4 weeks after primary surgery. The samples were processed for leukocyte separation on a Ficoll-Hypaque gradient and then used to prepare cytospin slides for immunocytochemical analysis. The slides were stained with a pool of monoclonal antibodies (MoAbs) which recognize tumor associated antigens, using the alkaline phosphatase anti-alkaline phosphatase method. The median follow-up was 36 months (range 15–62); 22 patients relapsed and 7 died. Results: Thirty-four of the 109 patients (31.1%) had MoAb positive bone marrow cells. The bone marrow was positive in 28/74 (37.9%) patients who had the aspirate taken during surgery and in 6/35 (17.1%) who had it taken after surgery (p = 0.055). No association was found between bone marrow positivity and tumour size, nodal status, menopausal status, estrogen receptor positivity or the proliferative index. No association was found between bone marrow and prognosis: the log-rank test was 0.291 (p 〉 0.5) for OS and 0.023 for DFS; the hazard ratio (positive vs negative) was 1.51 for OS (95% CI: 0.33–6.86) and 0.93 for DFS (95% CI: 0.35–2.45). Conclusions: In our series, bone marrow positivity did not correlate with prognostic parameters or prognosis. Of interest is the relative excess of positivity when the bone marrow was obtained during surgery.
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  • 86
    ISSN: 1573-7217
    Keywords: breast cancer ; carcinogenesis ; epidermal growth factor ; local recurrences ; saliva
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We measure EGF in saliva and plasma from 52 patients with active breast cancer, 22 breast cancer patients in follow-up (non-active) and 33 healthy women. EGF concentrations in saliva were significantly higher in patients with active and non-active breast cancer than healthy women, whereas the opposite results were found in plasma. The highest values of EGF in saliva were found in the local recurrence subgroup.
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  • 87
    ISSN: 1573-7217
    Keywords: apoptosis ; breast cancer ; cell cycle ; MCF-7 cells ; vitamin D analogs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the active metabolite of vitamin D, inhibits breast cancer cell growth both in vivo and in vitro. In addition to its anti-proliferative effects, 1,25(OH)2D3 induces morphological and biochemical markers of apoptosis in MCF-7 cells. In the studies reported here, we compared the effects of 1,25(OH)2D3 and EB1089, a low calcemic vitamin D analog, on cell cycle kinetics and apoptosis in MCF-7 cells. Both vitamin D compounds reduced viable MCF-7 cell number in a time and dose dependent manner, with EB1089 approximately 50 fold more potent than 1,25(OH)2D3. Flow cytometric analysis indicated that both agents induced cell cycle arrest in G0/G1 which was associated with accumulation of the hypophosphorylated form of the retinoblastoma (Rb) protein. MCF-7 cells treated with either 1,25(OH)2D3 or EB1089 for 48 h exhibited characteristics of apoptosis, including cytoplasmic condensation, pyknotic nuclei, condensed chromatin and DNA fragmentation. Cells treated with either agent exhibited up regulation of proteins associated with mammary gland regression (clusterin and cathepsin B) and down regulation of the anti-apoptotic protein bcl-2. These studies demonstrate that, despite its lower calcemic activity in vivo, the vitamin D analog EB1089 induces effects that are indistinguishable from those of 1,25(OH)2D3 on cell number, cell cycle and indices of apoptosis in MCF-7 cells in vitro. In addition, since both agents rapidly down regulate estrogen receptor, disruption of estrogen dependent signalling may play a role in the induction of apoptosis by vitamin D compounds in MCF-7 cells.
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  • 88
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    Breast cancer research and treatment 42 (1997), S. 235-242 
    ISSN: 1573-7217
    Keywords: breast cancer ; mammography ; post screen-detected cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The histological characteristics and extent of mammographic density were compared between 170 post screen-detected (PSD) breast cancers and 466 screen-detected (SD) breast cancers in women attending the Screening Mammography Program of British Columbia. In addition, methods of detection and clinical presentation for the PSD cancers were examined. Invasive ductal, comedo, and medullary carcinoma were significantly more common in PSD cancer in women under age 50 years, and invasive ductal carcinoma in women over age 50 years. Mammographic density was more common in PSD cancers for all age groups under 70 years. The majority of PSD cancers were node negative with no evidence of metastases; however, they tended to be of more advanced stage than SD cancer. Most PSD cancers regardless of age were initially found by the woman herself, presenting as a palpable mass, and the likelihood of being detected within 12 months of the last screening mammogram was higher at younger ages.
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  • 89
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    Breast cancer research and treatment 42 (1997), S. 275-281 
    ISSN: 1573-7217
    Keywords: breast cancer ; medical practice ; psychiatric history ; psychosocial morbidity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Studies to identify women with breast cancer who are at risk for psychosocial morbidity have identified several predictors, two of which are the focus of this study: 1) prior psychiatric history, and 2) poor initial emotional response to diagnosis. To examine current medical practice a survey was mailed to members of the Society of Surgical Oncology (response rate = 41.21%) asking how often they assess these two factors, reasons for not doing so, and asssessment methods. Results indicate that the majority rarely assess psychiatric history but frequently assess current emotional state, primarily using interview questions. Recommendations are presented to increase the likelihood of psychiatric assessment and enhance its value to the patient and physician.
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  • 90
    ISSN: 1573-7217
    Keywords: breast cancer ; DNA flow cytometry ; histological grade ; hormonal receptors ; premenopausal node-negative ; prognosis ; S+(G2+M)-phase fraction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The management of premenopausal node-negative breast cancer patients is discussed controversially. Accurate cellular as well as biochemical markers are essential for this cancer group to identify high risk patients needing adjuvant chemotherapy. In the present study, flow cytometric DNA analysis (DNA-ploidy status, DNA-index, S-phase fraction, S+(G2+M)-phase fraction) and clinico-pathological variables (clinical stage, tumor size, receptor status, age, histological type and grade) as prognostic factors were determined on paraffin-embedded tumors to predict overall survival (OS) and disease-free survival (DFS). Median observation time was 6.1 years (n = 57). S+(G2+M)-phase fraction was the only flow cytometric DNA predictor of overall survival in the univariate analysis (log-rank test): As compared to the patients with lower S+(G2+M)-phase fraction (≤ 9.3%), patients with S+(G2+M)-phase fraction greater than 9.3% had shorter survival (P = 0.039). Of all the clinico-pathological parameters analyzed (univariate analysis), the survival time was found to be longer when estrogen- and/or progesterone-receptor status was positive (overall survival: P = 0.039; disease-free survival: P = 0.017) and the histological grade was low (overall survival: I + II vs III: P = 0.024; I vs II vs III: P = 0.046). In the multivariate analysis, receptor status was the strongest predictor for overall and disease-free survival. These results suggest that S+(G2+M)-phase fraction in premenopausal node-negative breast cancer could be an additional valuable prognostic factor to classify high risk breast cancer patients needing adjuvant chemotherapy.
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  • 91
    ISSN: 1573-7217
    Keywords: breast cancer ; season ; circannual rhythm ; prolactin ; insulin-like growth factor-I ; melatonin ; cortisol ; growth hormone ; thyrotrophin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Hormones such as melatonin whose serum concentrations vary seasonally have been previously implicated in the growth of breast cancer. The present study was undertaken to identify possible seasonal variation in a range of mammotrophic hormones which could exert a chronobiologic influence in women with breast tumours. Fifteen premenopausal women with a history of previous breast cancer (BC subjects) and 10 control women underwent 2-hourly serum sampling for 24 h at both summer and winter solstice for measurement of melatonin, growth hormone (GH), insulin-like growth factor-I (IGF-I), cortisol, prolactin and thyrotrophin (TSH). Hormone secretion at the different seasons was compared by measuring the area under the 24 h serum hormone concentration × time curves and by time series analysis of summer-to-winter differences in hormone concentration. Control women had significantly higher GH and IGF-I levels in summer compared to winter and significantly higher cortisol secretion in winter than summer. In contrast, BC women had no significant seasonal difference in IGF-I concentrations and had a reversal of the normal seasonal pattern of melatonin secretion, although seasonal changes in GH production were similar to controls. Prolactin and TSH showed no significant summer/winter variation in either group. Thus, seasonal variations in hormone secretion seen in normal women were, with exception of GH, absent or reversed in women with a previous history of breast cancer. As a result these individuals may be exposed to an asynchronous hormonal stimulus which could influence tumour growth. These changes could reflect a constitutional abnormality in BC women or may have been induced by the previous breast tumour.
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  • 92
    ISSN: 1573-7217
    Keywords: estrogen metabolism ; breast cancer ; catecholestrogen ; estrone sulfatase ; noncancerous tissue
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to investigate the influence of estrogenmetabolism on human breast cancer, estradiol 2- and16α-hydroxylase (2- and 16α-OHase) activities were determined inthe microsomal fractions of cancer tissues by usingreverse phase HPLC. 2-OHase activity was detected inmost cancer tissues and noncancerous tissues, but theactivity was significantly lower in cancer tissues thanin the paired noncancerous tissues (0.01 〈 p〈 0.02). Interestingly the patients without lymph nodemetastasis had significantly higher 2-OHase activity in cancertissues than those with lymph node metastasis (0.02〈 p 〈 0.05). No correlation was observedbetween ER status and 2-OHase activity in cancertissues. On the other hand, 16α-OHase activity wasdetected only in one third of the breastcancer tissues examined. The activity was not significantlydifferent from that in noncancerous tissues, although itwas relatively higher in ER-positive cancer tissues whencompared with that in ER-negative ones (0.05 〈p 〈 0.1). Estrone sulfatase activity measured simultaneouslyin the cytosol fractions of some specimens wasmuch higher in cancer tissues than in noncanceroustissues (0.02 〈 p 〈 0.05). We found,however, no correlation between estrone sulfatase activity andestradiol hydroxylase activity. Taken together, our results suggestthat the increase in 2-OHase activity prevents theproliferation of breast cancer and that estradiol metabolismis regulated independently of the local biosynthesis ofestrogen.
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  • 93
    ISSN: 1573-7217
    Keywords: apoptosis ; breast cancer ; Bcl-2 ; Bax ; estradiol ; taxol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recent studies have demonstrated that following estrogen ablation, estrogen responsive breast cancer cells undergo apoptosis. In addition, estrogen receptor (ER) expression has been strongly correlated with the expression of the bcl-2 gene product, p26Bcl-2 protein, which is known to inhibit apoptosis. In the present studies, we investigated whether estrogen affects the intracellular levels of p26Bcl-2 and thereby modulates taxol-induced apoptosis of estrogen responsive human breast cancer MCF-7 cells. Transfer of MCF-7 cells to a culture-medium without estrogens reduced their intracellular p26Bcl-2 levels by 50%. Inclusion of 0.1 μM estradiol in the medium produced approximately a four-fold increase in p26Bcl-2, but not p29Bcl-xL or p21Bax levels; the expression of the c-myc and mdr-1 genes remained unchanged. Estradiol-induced four-fold increase in the ratio of the p26Bcl-2 to p21Bax levels caused a significant decline in the lethal, kilobase size DNA fragments of apoptosis, which had resulted when MCF-7 cells were cultured in a medium without estrogen. In addition, in MCF-7 cells, estradiol-induced increase in the intracellular p26Bcl-2 to p21Bax ratios was associated with a significant reduction in the large-sized DNA fragmentation induced by treatment with taxol. The increased ratios also protected MCF-7 cells against taxol-mediated cytotoxicity as assessed by the MTT assay. These results suggest that by modulating p26Bcl-2 levels, estrogens may affect the antitumor activity of taxol and potentially of other anti-breast cancer drugs against estrogen responsive human breast cancer cells.
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  • 94
    ISSN: 1573-7217
    Keywords: alpha-fetoprotein ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Alpha-fetoprotein (AFP) isolated from rodent amniotic fluid orhuman cord sera, upon incubation with a molarexcess of estradiol, is converted to a formwhich inhibits estrogen-stimulated tissue growth. The purpose ofthis study was to determine whether recombinant humanAFP produced in an E. coli expression systemretained this function. The recombinant protein was similarto the natural protein isolated from pooled humancord sera in all functional aspects evaluated. Itwas detected by monoclonal and polyclonal antibodies tothe natural protein. Following exposure to estradiol, itwas converted to an inhibitor of estrogen-stimulated growthof immature mouse uterus yielding a dose/response curvesimilar to that of the natural protein. Itinhibited the growth of estrogen-dependent (MCF-7) but notestrogen-independent (MDA-MB-231) breast cancer xenografts with the sameschedule dependency and resultant histological changes as thenatural protein. Availability of large quantities of homogeneous,biologically active recombinant human AFP will facilitate furtherstudies of structure/function, mechanism, and therapeutic potential ofthis agent as a regulator of breast cancergrowth.
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  • 95
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    Breast cancer research and treatment 45 (1997), S. 159-167 
    ISSN: 1573-7217
    Keywords: breast cancer ; surgery ; metastasis ; estrous cycle ; rat ; natural killer cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have previously reported sex- and estrous-related differences in hostresistance to the metastatic development of a mammary adenocarcinoma cellline, MADB106, in the Fischer 344 (F344) rat. In other studies, we foundthat surgery suppressed natural killer (NK) cell activity and increased theNK-sensitive metastatic development of MADB106 tumor cells. The currentstudy was designed to explore whether sex or estrous phase at the time ofsurgery impacts the degree of such deleterious effects of surgery. Suchestrous effects could be related to an ongoing clinical debate regarding theimportance of the timing of breast cancer surgery with the menstrual cyclein premenopausal women. Mature F344 males and cycling females underwenteither experimental laparotomy with halothane anesthesia, halothaneanesthesia alone, or were untreated. Five hours after surgery, animalseither were injected with radiolabeled MADB106 tumor cells and assessed forlung tumor cell retention 12 hours later, or underwent blood withdrawal forin vitro assessment of NK cell activity. MADB106 tumor cells metastasizeonly to the lungs, and lung tumor cell retention is: a) an early indicatorof the number of metastases that would develop weeks later, and b) highlysensitive to in vivo levels of NK activity. This mammary adenocarcinoma cellline is syngeneic to the inbred F344 strain of rats used in our studies,thus constituting a model for breast cancer metastasis. The resultsindicated that sex, estrous phase, and surgery interacted in their effectson NK cell activity and tumor metastasis. MADB106 lung tumor cell retentionwas increased by surgery in both sexes (2- to 3-fold) compared to theanesthesia only and control groups. This increase, however, wassignificantly greater in proestrus/estrus (P/E) females than inmetestrus/diestrus (M/D) females. Among the control animals, females in P/Eexhibited significantly less NK cytotoxic activity compared to the males,and the NK activity exhibited by females in M/D was between these twogroups. Surgery suppressed NK cytotoxic activity to a similar level in allgroups. Possible implications of these findings for the surgical care ofwomen with breast cancer are discussed.
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  • 96
    ISSN: 1573-7217
    Keywords: biochemistry ; breast cancer ; estrogen receptors ; immunohistochemistry ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Over the last few years, estrogen receptor determinationby means of immunohistochemistry has been extensively used.The aim of this study was to comparethis technique with estrogen receptor determination by meansof dextran-coated charcoal, and to evaluate whether oneof the two methods is more predictive ofprognosis. Estrogen receptors were determined by means ofboth the dextran-coated charcoal method and immunohistochemistry in405 patients with primary breast cancer; age, pathologicaltumor size, nodal status, and progesteron receptors bydextran-coated charcoal method were also recorded. The disease-freeand overall survival probabilities were estimated using theproduct-limit method; Cox's proportional hazard model was usedto evaluate the prognostic role of estrogen receptorsas determined by the two methods.There appears to be a close association betweenestrogen receptor determination by the two methods (81.5%of concordant results) and their prognostic role wassimilar, even when the patients were divided intodifferent groups (on the basis of their estrogenreceptor status) and adjustments for the effect ofother prognostic variables were taken into account. Ourstudy shows that the two methods can beused indifferently to evaluate estrogen receptor status asa prognostic factor in breast cancer patients.
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  • 97
    ISSN: 1573-7217
    Keywords: breast cancer ; response ; second-line endocrine therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study reports on factors predicting response tosecond-line endocrine therapy in 250 patients with breastcancer for which they were assessable for responseby the International Union Against Cancer (UICC) criteria.Clinical details relating to first-line endocrine therapy wereavailable for all patients. We have not includedin this study patients who received first-line endocrinetherapy but did not or have not yetproceeded to second-line hormone therapy – e.g. diedfrom rapidly progressive disease, started chemotherapy for rapidlyprogressive disease, or remained in long-term remission onfirst-line endocrine therapy.One hundred and fifty nine patients (72%) achievedremission (objective response and static disease [OR +SD]) on first-line endocrine therapy with a medianduration of 19 months. For second-line endocrine therapythe remission rate was 53% (132/225) with amedian duration of 15 months. Tumour grade andoestrogen receptor status of the primary tumour wereshown to be independent predictors of response tosecond-line endocrine therapy while response to first-line endocrinetherapy was a predictor of the duration ofresponse to second-line endocrine therapy. In the sub-groupof patients who showed OR or SD toboth first and second-line therapies, there was nocorrelation between the time to progression (TTP) onfirst and second-line therapies.
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  • 98
    ISSN: 1573-7217
    Keywords: DSA ; digital subtraction angiography ; breast cancer ; prognostic factor ; metastasis ; angiogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We examined the density of tumor enhancement onintravenous digital subtraction angiography (IV-DSA) in patients withbreast cancer in relation to disease-free survival. Thesubjects of the present study consisted of 103patients with invasive ductal carcinoma measuring 5 cmor less treated from July 1988 to September1993. In the 103 patients, 15 had distantmetastasis. The region of interest was set inthe areas enhanced by IV-DSA of the breast.The maximum density (MAX) was calculated by thetime-density curve. When the patients were divided accordingto three classes of MAX, i.e., 0–5.0 pixels(group A, n=23), 5.1–9.0 pixels (groupB, n=50), 9.1 pixels or more(group C, n=30), disease-free survival washighest in group A followed by group Band C, respectively. The disease-free survival rate ingroup C was significantly lower than that ofgroup A or B (p 〈 0.05). Thus,high values of MAX were associated with lowrates of disease-free survival. Since the value ofMAX was found to be independent from otherprognostic factors by multivariate analysis, these results indicatethat MAX has a close correlation with metastasisor recurrence of breast cancer, making IV-DSA apromising prognostic factor.
    Type of Medium: Electronic Resource
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  • 99
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 46 (1997), S. 181-189 
    ISSN: 1573-7217
    Keywords: breast cancer ; carcinogenesis ; carotenoids ; chemoprevention ; differentiation ; in vivo ; retinoids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In this review of the scientific literature the relationship between retinoids, carotenoids, and mammary carcinogenesis is examined. Several retinoids have shown promise as chemopreventive agents against chemically induced mammary carcinogenesis in mice and especially in rats. The most promising retinoids are retinyl acetate (RA) and N-(4-hydroxyphenyl)retinamide (4-HPR, fenretinide). In rats, dietary administration of these retinoids reduced tumor incidence and multiplicity, and increased the latency of DMBA or MNU-induced mammary cancers. In mice, 4-HPR reduced the number of hyperplastic alveolar nodules and the number of tumors in MTV- and MTV+ mice, respectively. Among retinoids, 4-HPR is at present the most promising analogue, due to its ability to concentrate in the mammary gland. The combination of 4-HPR with tamoxifen not only is more effective in suppressing breast cancer than either agent alone, but also inhibits the appearance of subsequent cancers following the surgical removal of the first tumor. These studies suggest that retinoids, like tamoxifen, may be applicable to the prevention of contralateral breast cancer in women who underwent breast cancer surgery. It is also becoming evident that differentiation therapy and chemoprevention can become attractive alternative approaches to intensive cytotoxic chemotherapy. The role of carotenoids in the prevention of mammary carcinogenesis, however, is ambiguous. Poor absorption and low levels of carotenoids that reach the target tissues complicate interpretation of data in rodent models of mammary carcinogenesis. Very few animal studies are presently available in which purified carotenoids were found effective against mammary carcinogenesis. These results do not justify undertaking clinical evaluation of individual carotenoids against breast cancer at this time.
    Type of Medium: Electronic Resource
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  • 100
    ISSN: 1573-7217
    Keywords: age ; breast cancer ; case-control study ; risk factors ; screening
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We examined the associations between reproductive factors and the risk of breast cancer on the basis of information from a total of 201,363 breast cancer screening program participants in Miyagi Prefecture, Japan, during 1987-1991. A case-control study method was applied on analysis. Data on 204 breast cancer cases identified and 810 screening year-, age- and screening area-matched normal controls were extracted. After adjustment for potential confounders, a trend of decreasing risk of breast cancer with increasing number of parity was observed (p for trend=0.03). Among parous women, lactation for the last child decreased the risk of breast cancer (odds ratio (OR) = 0.61, 95% confidence interval (95% CI) 0.39–0.94). These findings were consistent with those in clinical breast cancer reported previously. When cases were divided into two age groups, younger (≤ 49 y.o.) and older (50 y.o. ≤), family history of breast cancer among mother and sisters (OR=3.51, 95% CI 1.05–11.80), and lactation for the last child (OR=0.46, 95% CI 0.25–0.84) were associated with younger age breast cancer, whereas number of parity was associated with older age breast cancer (p for trend=0.03). The results by age group suggest that different mechanisms may exist in breast cancer developing at early and late onsets.
    Type of Medium: Electronic Resource
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