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  • 2005-2009
  • 1995-1999  (126)
  • 1999  (126)
  • breast cancer  (126)
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Material
Years
  • 2005-2009
  • 1995-1999  (126)
Year
Keywords
  • 1
    Electronic Resource
    Electronic Resource
    Effects of Experimental Chemoendocrine Therapy With a Combination of a Pure Antiestrogen and 5-Fluorouracil on Human Breast Cancer Cells Implanted in Nude Mice (1999)
    Springer
    Surgery today 29 (1999), S. 149-156 
    Details
    ISSN: 1436-2813
    Keywords: Key Words: chemoendocrine therapy ; pure antiestrogen ; 5-fluorouracil ; nude mouse ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s005950050376
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  • 2
    Electronic Resource
    Electronic Resource
    Effects of experimental chemoendocrine therapy with a combination of a pure antiestrogen and 5-fluorouracil on human breast cancer cells implanted in nude mice (1999)
    Springer
    Surgery today 29 (1999), S. 149-156 
    Details
    ISSN: 1436-2813
    Keywords: chemoendocrine therapy ; pure antiestrogen ; 5-fluorouracil ; nude mouse ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The antitumor effects of an experimental chemoendocrine therapy combining a new pure antiestrogen ICI 182780 and 5-fluorouracil (5-FU) were studied on MCF-7 human breast cancer cells implanted in nude mice. ICI 182780 had a dose-dependent antitumor activity, which was potentiated by the concomitant use of 5-FU. When compared with the control group, the estrogen receptor (ER) level in the ICI 182780 group was lower and that in the combination group was markedly lower. Cell cycle analysis by flow cytometry (FCM) resulted in a lower percentage of S-phase cells (%S) in the treated mice. No significant difference was observed in the 5-FU concentrations in tumor cells, while the 5-FU content in RNA was significantly higher in the combination group. The changes in free thymidylate synthetase (TS) concentration indicated TS synthesis after the administration of 5-FU to be more greatly suppressed in the combination group than in the 5-FU group. These results suggest that ICI 182780 and 5-FU exert their combination effect mainly on ER-positive cells, and that the suppression of TS synthesis in tumor cells and the potentiation of the 5-FU-induced metabolic dysfunction of RNA are thus involved in the mode of action of this combination therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02482240
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  • 3
    Electronic Resource
    Electronic Resource
    Vinorelbine as first-line chemotherapy for advanced breast cancer in women 60 years of age or older (1999)
    Springer
    Annals of oncology 10 (1999), S. 397-402 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; old age ; vinorelbine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Older patients with advanced breast cancer are less likely to receive chemotherapy than younger patients. Vinorelbine is an attractive alternative in this setting because of its clinical activity and low frequency of side effects. This multicenter, phase II trial was designed to assess the safety and efficacy of intravenous vinorelbine as first-line therapy in women ≥60 years old. Patients and methods: Fifty-six women (median age, 72 years; range 60–84 years), with measurable advanced breast cancer and no prior chemotherapy for metastatic disease, were enrolled and included in the analysis. Vinorelbine 30 mg/m2 was administered weekly for 13 weeks and then every two weeks until development of progressive disease; doses were reduced or delayed to manage toxicity. Results: The objective response rate was 38% (95% confidence interval (95% CI): 24%–51%); median duration of response, nine months; median time to disease progression in all patients, six months. The major dose-limiting toxicity was hematologic, which led to a median dose intensity of 20.6 mg/m2/week. Grade 3–4 nonhematologic toxicity consisted of asthenia (7%); nausea and generalized pain (5%); vomiting, chest pain, abdominal pain, and elevated AST (4%); fever, diarrhea, constipation, and injection site reaction (2%). Neurotoxicity and alopecia were grade 1–2 and relatively infrequent. Conclusions: Vinorelbine offers a promising alternative for the management of advanced breast cancer in elderly patients who are concerned about the subjective side effects of cytotoxic chemotherapy. The dose-limiting toxicity is neutropenia, which is readily managed with dose adjustment. Nonhematologic toxicity, including gastrointestinal side effects, is minimal. Randomized studies are warranted to compare the activity of vinorelbine with that of other regimens in elderly patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008364222793
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  • 4
    Electronic Resource
    Electronic Resource
    Upregulation of basic fibroblast growth factor in breast carcinoma and its relationship to vascular density, oestrogen receptor, epidermal growth factor receptor and survival (1999)
    Springer
    Annals of oncology 10 (1999), S. 707-713 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; fibroblast growth factor ; microvasculature
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Angiogenesis, the process whereby endothelial cells divide and migrate to form new blood capillaries, has been assessed in tumours by measuring microvessel density. High microvessel density is a significant adverse prognostic factor in breast cancer. The angiogenic factor, basic fibroblast growth factor (bFGF), has been associated with tumourigenesis and metastasis in several human cancers. There are few quantitative studies of bFGF expression in normal tissues compared to cancer. Patients and methods: We have measured bFGF levels in 149 human primary breast carcinomas and assessed the findings in relation to microvessel density, oestrogen receptor (ER) and epidermal growth factor receptor (EGFR). Basic FGF levels were measured by ELISA. Western blotting and immunohistochemistry were carreid out to confirm the presence of bFGF. Results: Levels of bFGF were more than 10-fold higher in tumour cytosols compared to reduction mammoplasty tissue and 3-fold compared to non neoplastic cytosols from the same breast as the tumour (P 〈 0.0001). Immunohistochemistry showed bFGF protein was localised exclusively in the stroma whereas no bFGF staining was observed in the epithelial cells. High bFGF levels were significantly related to high ER (P = 0.01). Similarly, high bFGF levels were significantly related to low grade (P = 0.046) and to small tumour size (P = 0.04). No significant relationship was observed between bFGF and microvessel count, EGFR or age. In univariate analysis and in a Cox proportional hazard model bFGF did not reach significance for overall or relapse free survival. Conclusions: Our results show that although bFGF is elevated in breast carcinomas compared to normal breast tissue it is not related to microvessel density and it is not an independent predictor of survival in breast cancer patients. Basic FGF may be one of multiple factors that synergise with other growth factors such as VEGF to enhance angiogenesis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008303614441
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  • 5
    Electronic Resource
    Electronic Resource
    ESTIC position paper: High-dose chemotherapy for breast cancer, investigation should continue (1999)
    Springer
    Annals of oncology 10 (1999), S. 903-905 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; high-dose chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008396811371
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  • 6
    Electronic Resource
    Electronic Resource
    The influence of familial and hereditary factors on the prognosis of breast cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 1163-1170 
    Details
    ISSN: 1569-8041
    Keywords: BRCA1 ; BRCA2 ; breast cancer ; family history ; survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Family history is a well recognized risk factor for breast cancer, but its impact in terms of breast cancer survival is uncertain. The recent identification of breast cancer predisposing genes has provided new clinical insights in this field. Design: English literature identified through Medline between 1976 and February 1999 was reviewed including search terms: breast cancer, survival, prognosis, family history, genetics, BRCA1, BRCA2, and related articles. Results: Publications were divided into three categories.Family history-based studies: eighteen articles were reviewed. Four studies showed a statistically significant better survival in patients with a family history of breast cancer, and two studies demonstrated a significantly worse prognosis in this context. The remaining articles showed no significant difference. Linkage studies: Two studies based on linkage to BRCA1 found that overall survival was better in linked families. A third one concluded to a worse outcome in BRCA2-linked tumors. Mutation-based studies: 10 studies looking at the association between germ-line mutations in BRCA1/BRCA2 and clinical outcomes were reviewed. Eight articles reported no significant difference in outcome, whereas two studies showed a worse outcome in patients with mutations. Conclusions: Conflicting data exist as to whether the prognosis of familial or hereditary breast cancer differs from that of sporadic cases. Some of the discrepancies may be explained by methodological differences or biases. However, no studies showed a survival advantage for BRCA1mutation carriers. This seems to indicate that BRCA1-related breast cancer is not associated with a survival advantage, and that in fact, certain BRCA1 germline mutations confer a worse prognosis. However, to adequately answer this question, more efficient molecular tools to identify all the genetic changes responsible for breast cancer predisposition, and large cohort studies to evaluate their clinical consequences, are needed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008301314812
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  • 7
    Electronic Resource
    Electronic Resource
    Local relapse in primary breast cancer patients with unexcised positive surgical margins after lumpectomy, radiotherapy and chemoendocrine therapy (1999)
    Springer
    Annals of oncology 10 (1999), S. 1451-1455 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; chemotherapy ; margins ; radiotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Inadequate surgical excision with residual involvement of resection margins by tumour after breast conservation results in increased local recurrence rates. To reduce this risk positive margins are, therefore, usually excised. Systemic treatment with tamoxifen or chemotherapy reduces local recurrence, along with radiotherapy. However, no studies to date have examined the correlation between chemoendocrine treatment, together with radiotherapy, and local relapse in patients with unexcised involved resection margins, having had breast conservation treatment. Patients and methods: The histopathology reports were reviewed of 184 patients who were treated from June 1991 to August 1995 within our randomised study of neoadjuvant versus adjuvant chemoendocrine therapy with mitozantrone and methotrexate (2M) ± mitomycin-C (3M) and tamoxifen, used concurrently with radiation following conservation surgical treatment. Histological resection margin was considered positive if ductal carcinoma in situ (DCIS) or invasive carcinoma was present microscopically less than 1mm from the excision margin. Results: Although 38% of patients had unexcised microscopically involved margins, local relapse rate as first site of relapse was only 1.9% after a median follow up of 57 months. There was no difference in distant relapse (P = 0.2) and survival (P = 0.5) between the positive and negative margins groups. Conclusions: The presence of positive unexcised margins does not have a significant effect on outcome in patients who are treated with chemoendocrine therapy together with radiotherapy. Further clinical trials are required.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008371318784
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  • 8
    Electronic Resource
    Electronic Resource
    Docetaxel in the community setting: An analysis of 377 breast cancer patients treated with docetaxel (Taxotere®) in the UK (1999)
    Springer
    Annals of oncology 10 (1999), S. 205-210 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; docetaxel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Given as first- or second-line chemotherapy, docetaxel appears to have great potential in advanced breast cancer. Patients and methods: Three hundred and seventy-seven locally advanced or metastatic breast cancer patients received docetaxel (Taxotere®) as part of a named patient programme under the care of 108 oncologists from 61 cancer units across the UK. The recommended starting dose was 100 mg/m2, but patients at higher risk of toxicity started at 75 mg/m2. All patients received corticosteroid premedication. The modal number of prior chemotherapy regimens was 2 (range 1–7), 342 patients (91%) had at least one prior anthracycline-based regimen. Results: Response was graded according to the managing clinician's best judgement without formal criteria. The overall response rate (ORR) was 46% among the 331 evaluable patients, 46% among the 299 patients who were 'anthracycline resistant' and 35% among the 82 patients who were 'anthracycline refractory' (progressive disease being the best response obtained to the most recent anthracycline containing regimen). One hundred and ninety-three patients started at the full dose of 100 mg/m2 with an ORR of 55% and 129 started at 75 mg/m2 with an ORR of 33%. In October 1997, some two years after the programme had started, 26 of 377 patients were still alive, although no complete remissions have lasted to this date. Kaplan–Meier survival analysis yielded a median survival of 194 days (95% CI: 178–218 days). Haematological parameters were checked before each course of docetaxel and additionally as clinically indicated. The safety data confirmed that docetaxel has a manageable, predictable side effect profile; 29 of 377 (7.7%) patients were hospitalised as a result of neutropenic sepsis. Conclusions: The results of this named patient programme over a two year timespan confirm that docetaxel is an effective chemotherapy option in patients with locally advanced and/or metastatic breast cancer, including an 'anthracycline refractory' population.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008370930599
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  • 9
    Electronic Resource
    Electronic Resource
    Phase II study of epirubicin and vinorelbine with granulocyte colony-stimulating factor: A high-activity, dose-dense weekly regimen for advanced breast cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 937-942 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; dose-intensity ; epirubicin ; G-CS/kwd〉 ; vinorelbine ; weekly schedule
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: This study was designed to explore the effectiveness and tolerability of a weekly regimen of epirubicin and vinorelbine plus granulocyte colony-stimulating factor (G-CSF). Patients and methods: Fifty-two patients with previously untreated advanced breast cancer were treated with epirubicin (25 mg/m2/week) and vinorelbine (25 mg/m2/week) with G-CSF support, for 24 consecutive weeks. Results: The median number of courses per patient was 22 (range 10–24). The administered dose intensity was 23 mg/m2 for both epirubicin and vinorelbine. Ten complete responses (19%) and 30 partial responses (58%) were obtained, for an overall response rate of 77%. None of the patients progressed during treatment. The median response duration and time to progression were both 10 months. A total of 1065 courses were assessed for toxicity. Grade 3 neutropenia was the most common toxic manifestation, (39% of patients), without febrile neutropenia or neutropenic sepsis. Two patients had grade 3 cardiac toxicity, which regressed without sequelae. Median survival was 31 months, with a median follow-up of 24 months (range 9–40). Conclusions: Owing to its effectiveness and tolerability, the weekly regimen of epirubicin and vinorelbine plus G-CSF may represent an acceptable alternative for patients with untreated metastatic breast cancer. It could be tested in the adjuvant and neoadjuvant setting.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008324329562
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  • 10
    Electronic Resource
    Electronic Resource
    Paclitaxel by 24-hour infusion with doxorubicin by 48-hour infusion as initial therapy for metastatic breast cancer: Phase I results (1999)
    Springer
    Annals of oncology 10 (1999), S. 403-411 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; doxorubicin ; paclitaxel-anthracycline combination ; schedule
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: We and others have demonstrated the antineoplastic efficacy of paclitaxel as a single agent in metastatic breast cancer. We performed this phase I trial to evaluate the combination of paclitaxel with doxorubicin. Patients and methods: Eligible patients had measurable or evaluable metastatic breast cancer for which this was the initial cytotoxic treatment. They may have received adjuvant chemotherapy with other drugs. The study had four parts. In part 1, the patients received paclitaxel by 24-hour infusion followed by doxorubicin by 48-hour infusion. The paclitaxel dose was to be escalated from a starting dose of 125 mg/m2, and the doxorubicin dose was to remain constant at 60 mg/m2 with treatment repeated every three weeks. The results of part 1 prompted part 2 which was a study of the reverse sequence. Part 3 was a formal study of pharmacology and has been reported (J Clin Oncol 14: 2713–21, 1996). In part 4, patients received doxorubicin 50 mg/m2 by bolus followed by paclitaxel 150 mg/m2 by 24-hour infusion for courses 1 and 2. In all subsequent courses doxorubicin was administered by 48-hour infusion. All patients in all four parts of the study had baseline cardiac scans. All patients received standard premedication for paclitaxel. Results: Forty-eight patients were treated in all four parts of the study. In part 1 (10 patients), the maximum tolerated dose (MTD) was paclitaxel 125 mg/m2/24 hours followed by doxorubicin 48 mg/m2/48 hours as defined by dose-limiting mucositis and neutropenic fever which occurred at the starting dose. For part 2 (21 patients), the MTD was doxorubicin 60 mg/m2/48 hours followed by paclitaxel 160 mg/m2/24 hours. In part 4 (seven patients), the MTD was doxorubicin 50 mg/m2/bolus followed by paclitaxel 135 mg/m2/24 hours. In parts 2 and 4, the dose-limiting toxic effect was neutropenia. Of the entire cohort of 48 patients, seven (15%) had a complete response (one persists at five years without intervening therapy), 26 (54%) had a partial response for an objective response rate of 69% (95% confidence interval (95% CI): 54%–81%). The median follow-up of all living patients is 38+ months (range 20+ to 62+); the median response duration is seven months (range 2–33.7+); the median overall survival is 20.5 months (range 5–54+). The median time to progression is 9.6 months (range 1–33.7+ months). Two patients developed congestive heart failure, one at 24 months after her final dose of doxorubicin which amounted to a cumulative lifetime total doxorubicin dose of 870 mg/m2, one after a total of 660 mg/m2. In both, cardiac symptoms were controlled with medications. Conclusions: The combination of paclitaxel/24 hours with doxorubicin/48 hours is an effective antineoplastic treatment for metastatic breast cancer. However, the incidence of complete response, the median overall survival, and time to progression were not greater than for standard doxorubicin-based combinations. Additionally, a sequence-dependent interaction between paclitaxel and doxorubicin, given in the schedule described here, was defined. Other strategies and schedules should be evaluated to maximize the antineoplastic efficacy of these two potent agents.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008360406322
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  • 11
    Electronic Resource
    Electronic Resource
    Primary chemotherapy in operable breast cancer with favorable prognostic factors: A pilot study evaluating the efficacy of a regimen with a low subjective toxic burden containing vinorelbine, 5-fluorouracil and folinic acid (FLN) (1999)
    Springer
    Annals of oncology 10 (1999), S. 993-996 
    Details
    ISSN: 1569-8041
    Keywords: 5-fluorouracil ; breast cancer ; neoadjuvant ; primary chemotherapy ; vinorelbine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Biological considerations support the use of primary chemotherapy in operable breast cancer; and despite wide variations of used regimens, clinical studies consistently show a significant tumor response allowing breast conservation in many patients otherwise canditates for mastectomy. We investigated the efficacy and the acceptance of a combination chemotherapy with vinorelbine, 5-fluorouracil and high-dose folinic acid in operable breast cancer with favorable prognostic factors and tested the relationship of hormone receptor status, Ki67, p53, c-erbB2 and bcl-2 with treatment response. Patients and methods: Thirty-nine patients (median age 51 years, range 36–71 years), eight with T1, twenty-eight with T2 and two with T3 lesions, were treated with 5-fluorouracil (350 mg/m2, i.v. on day 1 to 3) preceded by folinic acid (100 mg/m2 i.v. on day 1 to 3) and vinorelbine, given on days 1 and 3 at the dose of 20 mg/m2 (FLN regimen). Therapy was administered on an outpatient basis every three weeks. Non responders had surgery after three courses, while complete or partial responders underwent surgery after six courses. All but one were evaluable for response and toxicity. Results: Objective responses were observed in 23 of the 38 evaluable patients (61%; 95% CI: 46%–76%): three complete responses (8%) and 20 partial responses (53%). Fifteen patients (39%) had stable disease, of whom nine (23%) had minor response. None of the patients had disease progression during treatment. Objective responses were significantly associated with no expression of estrogen and/or progesteron receptors and 〉50% decrease in Ki67 after induction chemotherapy. Tolerance was excellent and none of the patients experienced grade 2 alopecia. Conclusions: The ‘moderate’ efficacy of this regimen might be partially due to the selection of patients with high expression of steroid hormone receptors and low proliferation rate, which have an unfavorable impact on response to this chemotherapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008389106575
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  • 12
    Electronic Resource
    Electronic Resource
    Cardiac effects of high-dose epirubicin and cyclophosphamide in women with poor prognosis breast cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 53-58 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; cardiotoxicity ; cyclophosphamide ; epirubicin ; high dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To prospectively evaluate the long term cardiac effects of high-dose epirubicin and cyclophosphamide given to women with early stage, poor prognosis breast cancer. Patients and methods: Women with stage 2 breast cancer and 10+ nodes or 4+ nodes and estrogen receptor negative tumor, or stage 3 breast cancer received three cycles of epirubicin 200 mg/m2 and cyclophosphamide 4 gm/m2 with peripheral blood progenitor cell and filgrastim support. Treatment was given every 28 days (n = 79) or 21 days (n = 20). Fifty patients received radiotherapy to the chest wall or breast, 25 of to the left side. Patients were assessed clinically regularly during chemotherapy and at least three times yearly after completion of treatment. Cardiac left ventricular ejection fraction (LVEF) was assessed by radionuclide scan before therapy, after each cycle of chemotherapy, three months and six months after completion of chemotherapy, and yearly thereafter until relapse. Results: Ninety-nine women were treated, and 92 completed all three cycles of chemotherapy. The median age was 43 years (range 24 to 60 years). All patients were included in this analysis. The median relapse-free survival was 39 months (11 to 68 months). There was a significant fall in LVEF during chemotherapy. In general, there was no further deterioration in cardiac function from the third month after cessation of treatment, however there was substantial variation between individuals. 35 patients had at least one LVEF measure less than normal (〈50%), but the LVEF returned to normal in 20 of these with further follow-up. Cardiac dysfunction was not increased in women who received radiotherapy and was not different between cohorts given chemotherapy every three or every four weeks. One patient died of acute myocardial necrosis following the third cycle of chemotherapy. Two patients developed clinical evidence of cardiac failure, and another had radiological signs but was asymptomatic. One woman died of progressive cardiac failure, one recovered clinically but also developed recurrent breast cancer, while the third recovered after commencement of medical therapy. Conclusions: During follow-up after high-dose epirubicin and cyclophosphamide as delivered in this study, the LVEF fell to below normal in approximately one third of patients. However, in over half of these patients the LVEF subsequently recovered to the normal range, and the incidence of clinically evident chronic cardiac failure was low. Further follow-up is required to assess the long- term safety. A randomized comparison with standard-dose anthracycline-based chemotherapy is needed to determine whether this regimen is associated with an increased risk of clinical cardiac toxicity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008390203340
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  • 13
    Electronic Resource
    Electronic Resource
    Breast cancer screening by mammography in Norway. Is it cost- effective? (1999)
    Springer
    Annals of oncology 10 (1999), S. 197-203 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; cost-effectiveness ; mammography ; screening
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Mammography screening is a promising method for improving prognosis in breast cancer. Patients and methods: In this economic analysis, data from the Norwegian Mammography Project (NMP), the National Health Administration (NMA) and the Norwegian Medical Association (NMA) were employed in a model for cost-effectiveness analysis. According to the annual report of the NMP for 1996, 60,147 women aged 50–69 years had been invited to a two-yearly mammographic screening programme. 46,329 (77%) had been screened and 337 (0.7%) breast cancers had been revealed. The use of breast conserving surgery (BCS) was in this study estimated raised by 17% due to screening, the breast cancer mortality decreased by 30% and the number of life years saved per prevented breast cancer death was calculated 15 years. Results: The cost per woman screened was calculated £75.4, the cost per cancer detected £10,365 and the cost per life year (LY) saved £8,561. A raised frequency of BCS, diagnosis and adjuvant chemotherapy brought two years forward, follow-up costs and costs/savings due to prevented breast cancer deaths were all included in the analysis. A sensitivity analysis documented mammography screening cost-effective in Norway when four to nine years are gained per prevented breast cancer death. Conclusion: Mammography screening in Norway looks cost- effective. Time has come to encourage national screening programmes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008376608270
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  • 14
    Electronic Resource
    Electronic Resource
    The third-generation non-steroidal aromatase inhibitors: A review of their clinical benefits in the second-line hormonal treatment of advanced breast cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 377-384 
    Details
    ISSN: 1569-8041
    Keywords: anastrozole ; aromatase inhibitors ; breast cancer ; hormonal therapy ; letrozole ; review ; vorozole
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Three new aromatase inhibitors have recently completed phase III evaluation as treatment of metastatic breast cancer in post-menopausal women whose disease has progressed despite tamoxifen therapy: anastrozole (ARIMIDEX, Zeneca), letrozole (FEMARA, Novartis) and vorozole (RIVIZOR, Janssen). All belong to the third generation of non-steroidal aromatase inhibitors, and each is superior to previous generations in terms of potency and selectivity. The trials that have been performed compare each agent to megestrol acetate, and letrozole and vorozole to aminoglutethimide. Although the studies are not directly comparable due to differing study designs and patient populations, it has been demonstrated each of these drugs provides single agent, once-daily, oral palliation of hormone-responsive, post-menopausal metastatic breast cancer. Letrozole is clearly more effective than megestrol acetate, and anastrozole and vorozole are possibly so. All three are better tolerated than the progestin, particularly in terms of weight gain. Both letrozole and vorozole are significantly more effective, and better tolerated than aminoglutethimide. Overall, this most recent generation of aromatase inhibitors is a clear improvement on our current standard second-line therapies. In 1999, tamoxifen remains the first choice in the hormonal therapy of breast cancer. Following tamoxifen failure, the optimal second-line hormonal therapy remains undefined, but aminoglutethimide and megestrol acetate are no longer optimal therapy in this setting. The third-generation non-steroidal aromatase inhibitors must now be compared to each other, to the steroidal aromatase inhibitors, to the pure anti-oestrogens, and to tamoxifen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008368300827
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  • 15
    Electronic Resource
    Electronic Resource
    Synchronous inflammatory breast cancer and advanced ovarian carcinoma: A case with prolonged disease-free survival (1999)
    Springer
    Annals of oncology 10 (1999), S. 585-588 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; cisplatin ; ovarian cancer ; paclitaxel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Despite the known association of these malignancies, the incidence of a synchronous presentation of breast and ovarian cancer is low, and the current literature does not address an approach to this clinical problem directly. We report a greater than 2.5 year disease-free survival in a patient treated for synchronous stage IIIB inflammatory breast cancer and stage IIIC epithelial ovarian cancer. The prolonged disease-free survival in our case may provide some guidance in this unusual clinical situation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008239124657
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  • 16
    Electronic Resource
    Electronic Resource
    Autologous stem-cell transplant after conventional dose adjuvant chemotherapy for high-risk breast cancer: Impact on the delivery of local-regional radiation therapy (1999)
    Springer
    Annals of oncology 10 (1999), S. 929-936 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; local regional therapy ; stem-cell transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: High-dose chemotherapy with autologous stem-cell transplantation is used increasingly in the treatment of poor-prognosis primary breast cancer. Because these patients may be cured with standard multimodality therapy, it is important to address both the efficacy of transplantation, and its effect on the delivery of standard treatments including local radiation therapy. Patients and methods: Patients with high risk primary breast cancer were treated with high-dose cyclophosphamide and thiotepa and stem-cell transplant following surgery and conventional-dose adjuvant chemotherapy. Outcome, including sites of failure and delivery of local radiation therapy, was assessed for 103 patients. Results: Overall and disease-free survival rates at 18 months were 83% (± 4%) and 77% (± 4%) respectively. Twenty patients (19.4%) received radiation therapy prior to transplant. Of the remaining 83, 77 received radiation therapy after transplant. Overall, 5 (19.2%) of 26 first sites of recurrence were local alone. For patients receiving radiation prior to transplant, 3 of 7 (43%, 95% CI: 6%–80%) sites of first recurrence were local, while 2 of 19 (10.5%, 95% CI: 0%–24.5%) sites of first recurrence were local alone in patients receiving post-transplant radiation or no radiation. Conclusion: Transplantation does not appear to significantly compromise the delivery or outcome of local radiation therapy for primary breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008393204854
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  • 17
    Electronic Resource
    Electronic Resource
    Adjuvant Therapy of Breast Cancer: Update (1999)
    Springer
    Annals of oncology 10 (1999), S. 129-137 
    Details
    ISSN: 1569-8041
    Keywords: adjuvant treatment ; breast cancer ; systemic therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The theoretical prediction that breast cancer is a systemic disease, and that patients may benefit from addition of systemic therapy to local treatment, has now been confirmed by three decades of clinical investigations. A long-term follow up of individual trials and the International Overview based on meta-analyses clearly showed the potential of both hormonal therapies and chemotherapy to prolong disease-free and overall survival in nearly all groups of patients. The benefits have been demonstrated for both premenopausal and postmenopausal patients, with both node-negative and node-positive disease. However, there is still considerable uncertainty regarding the most appropriate treatment for each individual patient. In the present review, the results of meta-analysis are highlighted in the context of the new trials supporting the value of chemoendocrine therapy and anthracycline-based therapy. The results of prospective randomised trials evaluating the role of dose intensification, drug sequencing and dose density are discussed. Also presented are new treatment strategies, such as preoperative chemotherapy and high-dose chemotherapy with stem cell support, the value of which remains to be confirmed. Future possibilities opened by inclusion of biologics into adjuvant therapy are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008362521127
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  • 18
    Electronic Resource
    Electronic Resource
    New Developments in Chemotherapy of Advanced Breast Cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 139-146 
    Details
    ISSN: 1569-8041
    Keywords: anthracycline ; breast cancer ; chemotherapy ; HER-2 antibody ; N,N-diethyl-2[4-(phenylmethyl)-phenoxy] ethanamine.HCl (DPPE, BMS-217380-01) ; paclitaxel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Anthracyclines and taxanes are the two most active classes of chemotherapy for the treatment of advanced breast cancer. Recent studies have investigated combination therapy including doxorubicin (Dox) and paclitaxel. The efficacy of this combination has been established in a phase III study conducted by ECOG, comparing Dox/paclitaxel versus Dox versus paclitaxel. The combination is superior to Dox or paclitaxel with respect to response rate and time to disease progression, indicating that the combination provides a new standard for the first line treatment of metastatic breast cancer [1]. Phase II studies using higher doses of Dox and using shorter infusions of paclitaxel have suggested the combination can be further optimised; Gianni reported a 94% objective response rate using Dox 60 mg/m2 followed by paclitaxel 175 mg/m2 given over three hours [2]. The more active regimens are associated with enhanced cardiotoxicity; this toxicity can be avoided, however, by limiting the exposure to doxorubicin. The newer regimens have now been moved into phase III studies. Future progress for this disease will depend on the introduction of new agents. Two novel drugs are currently being investigated in randomised phase III trials as potentiators of Dox and/or paclitaxel. One is a monoclonal antibody from Genentech (Herceptin, trastuzumab) directed at the HER-2/neu oncogene, which is overexpressed in 〉25% of breast cancers [3]. Recent results indicate that Herceptin in combination with paclitaxel (or with a Dox plus cyclophosphamide regimen) induces a higher response rate (RR) and prolongs the time to disease progression when compared to chemotherapy alone. The second agent N,N-diethyl-2[4-(phenylmethyl)-phenoxyl] ethanamine.HCl (DPPE, BMS-217380-01), when combined with Dox, was associated with a higher RR than previously observed with Dox alone [4]. A randomised trial of Dox versus Dox plus DPPE is ongoing. The possible mechanisms underlying chemo-potentiation by these agents are discussed. As new anthracycline/taxane combinations establish themselves in earlier stages of the disease, the need for effective, non-cross resistant salvage regimens will emerge.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008318725670
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  • 19
    Electronic Resource
    Electronic Resource
    Cowden disease and Lhermitte Duclos disease, markers of breast carcinoma: Report of two patients (1999)
    Springer
    Annals of oncology 10 (1999), S. 1241-1243 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; Cowden disease ; Lhermitte Duclos
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008317923860
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  • 20
    Electronic Resource
    Electronic Resource
    A randomized, open, parallel-group trial to compare the endocrine effects of oral anastrozole (Arimidex®) with intramuscular formestane in postmenopausal women with advanced breast cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 1219-1225 
    Details
    ISSN: 1569-8041
    Keywords: anastrozole ; Arimidex® ; aromatase inhibitor ; breast cancer ; formestane ; oestradiol ; tolerability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: This study provides a direct randomized comparison of a new-generation, non-steroidal aromatase inhibitor, anastrozole (Arimidex®), with a steroidal aromatase inhibitor (formestane) with respect to oestrogen (oestradiol, oestrone, and oestrone sulphate) suppression and tolerability. Patients and methods: Sixty postmenopausal women with advanced breast cancer were randomized to receive either anastrozole 1 mg once daily orally (n = 29), or formestane 250 mg once every two weeks by intramuscular injection (n = 31). Treatment was continued until progression of disease or withdrawal from the study. The primary endpoints of this study were oestradiol suppression and tolerability. The secondary endpoints included oestrone and oestrone sulphate suppression. All laboratory analyses were conducted ‘blind’ of the randomized drug treatment. Results: Anastrozole produced a greater and more consistent suppression of oestradiol levels compared with formestane. Based on two- and four-week measurements, the mean fall from baseline (pre-dose) in oestradiol level was 79% and 58% in the anastrozole and formestane groups, respectively (P = 0.0001). After four weeks of treatment, oestrone and oestrone sulphate levels were also suppressed to a greater extent by anastrozole compared with formestane (oestrone: 85% versus67%, respectively, P = 0.0043; oestrone sulphate: 92% versus 67%, respectively, P = 0.0007). No statistical differences were seen between the two drugs in the incidence of adverse events. Conclusions: Anastrozole provides a more consistent and significantly more effective suppression of oestradiol compared with formestane. Similar results were observed for oestrone and oestrone sulphate. The clinical significance of these differences in total oestrogen suppression remains to be established.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008308609325
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  • 21
    Electronic Resource
    Electronic Resource
    Screening Mammography for Early Detection of Breast Cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 121-127 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; mammography ; prevention ; screening
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract From numerous studies on breast cancer it can be concluded that no single measure can lessen the burden of this frequent cancer in women in all developed countries. Complex strategies including primary prevention by identification of risk factors and their modification, secondary prevention by earlier detection and tertiary prevention by improving treatment outcome are needed to control the disease. Besides age, the established breast cancer risk factors include certain benign breast diseases, family history, ionising radiation, some reproductive factors and obesity. Primary prevention includes general recommendation for healthy lifestyle, e.g., avoidance of obesity, proper diet, physical activity and moderate alcohol consumption. Randomised controlled trials conducted in the USA, Canada, Scotland and Sweden have shown that regular mammography, alone or in combination with clinical examination, is effective in reducing mortality for about 30% in women over the age of 50, and much less in younger population. However, mammography screening has several drawbacks, the major being its tendency towards false positive and false negative results with all their potential psychosocial consequences. High quality assurance and control, as well as effective and readily available treatment, all of which demand high investments, are indispensable for good results. Even in the absence of organised screening, the availability of effective treatment may contribute to reduction in breast cancer mortality.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008310503380
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  • 22
    Electronic Resource
    Electronic Resource
    Cytomegalovirus pneumonia in a patient with breast cancer on chemotherapy: Case report and review of the literature (1999)
    Springer
    Annals of oncology 10 (1999), S. 461-465 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; cytomegalovirus pneumonia ; dexamethasone ; ganciclovir ; standard dose chemotherapy regimen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cytomegalovirus (CMV) pneumonia in the setting of non-transplantation patients is a rarity. We present a case of CMV pneumonitis in a woman with stage IV breast cancer, with brain metastases, receiving both chemotherapy and systemic corticosteroids. A review of the literature reveals this as a unique case. Potential viral etiologies should therefore be considered in cancer patients with pneumonia receiving non-transplantation chemotherapy-regimens, particularly if steroids are a component of their therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008360927507
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  • 23
    Electronic Resource
    Electronic Resource
    Front-line treatment of metastatic breast cancer with docetaxel and epirubicin: A multicenter dose-escalation study (1999)
    Springer
    Annals of oncology 10 (1999), S. 547-552 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; docetaxel ; epirubicin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To determine the maximum tolerable dose (MTD) and the dose-limiting toxicity (DLT) of docetaxel (D) in combination with epirubicin (Epi) in patients with advanced breast cancer. Patients and methods: Forty-seven chemotherapy-naïve metastatic breast cancer patients aged 〈75 years with PS (WHO) 0–2 and adequate bone marrow, renal, liver and cardiac function, were enrolled in the study. Epi was given as a five-min bolus i.v. infusion on day 1 (d1) in escalated doses with increments of 10 mg/m2; D was given in a one-hour infusion after appropriate premedication on either day 1 or on day 2 in escalated doses with increments of 10 mg/m2. The patients' median age was 60 years, 42 (89%) had a PS (WHO) 0–1, 16 (34%) were premenopausal and 25 (53%) had visceral disease. Results: When the two drugs were given on the same day, the MTD1 was reached at the doses of Epi 60 mg/m2 and D 80 mg/m2; administration of G-CSF could not result in a dose intensification. When the drugs were given on two consecutive days, the MTD2 was reached at the doses of Epi 80 mg/m2 (d1) and D 90 mg/m2 (d2). The dose-limiting events were febrile neutropenia and grade 4 neutropenia, which developed in 30 (64%) patients during the study; among 227 delivered cycles grade 3–4 neutropenia occurred in 64 (28%) cycles but only 22 (10%) of them were complicated by fever. There were no septic deaths. Grade 1–2 neurosensory toxicity occurred in nine (19%) patients, mild edema in eight (17%) and allergic reactions in five (11%). Four (9%) patients presented a greater than 10% decrease of LVEF and treatment discontinuation was required in two of them; none of the patients developed congestive heart failure. Nevertheless, one patient suddenly died 10 days after treatment initiation of myocardial ischemia, and this death is considered treatment-related. Five (14.7%) complete and thirteen (38.2%) partial responses (ORR: 53.9%; 95% confidence interval: 36.1%–69.7%) were observed in 34 evaluable patients. Ten (29.4%) and six (17.6%) patients had stable and progressive disease, respectively. The median duration of response and time to tumor progression were five and seven months, respectively. The median survival has not yet been reached. Conclusions: The combination of epirubicin and docetaxel is a feasible and well tolerated regimen, but the MTD depends on the administration schedule of the drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026441804889
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  • 24
    Electronic Resource
    Electronic Resource
    Depression in breast cancer patients: The need for treatment (1999)
    Springer
    Annals of oncology 10 (1999), S. 627-636 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; depression ; diagnosis ; treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008328005050
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  • 25
    Electronic Resource
    Electronic Resource
    A phase I study of sequential vinorelbine followed by paclitaxel (1999)
    Springer
    Annals of oncology 10 (1999), S. 861-863 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; paclitaxel ; phase I ; vinorelbine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: In vitro experiments suggest that administration of vinorelbine preceding paclitaxel results in synergistic cytotoxic effects. A phase I dose escalation trial of vinorelbine daily × 3 with paclitaxel on day 3 repeated every 28 days in metastatic breast cancer patients was completed. Patients and methods: Female patients, PS 0–2, without evidence of CNS disease or prior neuropathies were treated with vinorelbine at dose levels 7, 10, 13 mg/m2 per day and paclitaxel over three hours at dose levels of 135, 175, and 200 mg/m2. Results: Twenty-eight patients with six dose levels were studied. At dose level 1, patients developed intolerable but reversible neutropenia. Subsequent dose levels required filgrastim. Dose limiting toxicities were myalgia and fatigue at vinorelbine 13 mg/m2 /day and paclitaxel 200 mg/m2. Neuropathy was minor. Twelve of twenty-five patients with measurable disease had a rapid response which did not correlate with dose level. Conclusions: Sequential administration of these two agents demonstrates activity in breast cancer patients. Phase II dosing on this schedule should be vinorelbine 13 mg/m2/day × 3 and paclitaxel 175 mg/m2. With proper selection of patients, concern about neurologic toxicity should not impede future trials of vinorelbine with paclitaxel.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008351915582
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  • 26
    Electronic Resource
    Electronic Resource
    Ala99ser mutation in RIα Regulatory Subunit of protein kinase A causes reduced kinase activation by cAMP and arrest of hormone-dependent breast cancer cell growth (1999)
    Springer
    Molecular and cellular biochemistry 195 (1999), S. 77-86 
    Details
    ISSN: 1573-4919
    Keywords: protein kinase A ; site-directed mutagenesis ; breast cancer ; growth arrest ; cAMP response element
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Expression of the RIα regulatory subunit of protein kinase A type I is increased in human cancer cell lines, in primary tumors, in cells after transformation, and in cells upon stimulation of growth. Ala99 (the pseudophosphorylation site) of human RIα was replaced with Ser (RIα-p) for the structure-function analysis of RIα. MCF-7 hormone- dependent breast cancer cells were transfected with an expression vector for the wild-type RIα or mutant RIα-p. Overexpression of RIα-P resulted in suppression of protein kinase A type II, the isozyme of type I kinase, production of kinase exhibiting reduced cAMP activation, and inhibition of cell growth showing an increase in G0/G1 phase of the cell cycle and apoptosis. The wild-type RIα overexpression had no effect on protein kinase A isozyme distribution or cell growth. Overexpression of protein kinase A type II regulatory subunit, RIIβ, suppressed RIα and protein kinase A type I and inhibited cell growth. These results show that the growth of hormone-dependent breast cancer cells is dependent on the functional protein kinase A type I.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006934113439
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  • 27
    Electronic Resource
    Electronic Resource
    Agonist and antagonist-induced qualitative and quantitative alterations of progesterone receptor from breast cancer cells (1999)
    Springer
    Molecular and cellular biochemistry 199 (1999), S. 49-56 
    Details
    ISSN: 1573-4919
    Keywords: progesterone receptor ; breast cancer ; steroid receptor agonists ; antagonists ; T47D cells ; RU486
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract T47D cells, cultured in medium containing serum stripped of endogenous steroids, proliferate in response to treatment with the progesterone receptor (PR) agonist, R5020 or the PR agonist/antagonist, RU486, whereas the full PR antagonist, ZK98299 has no proliferative effects. Under estrogenized conditions, all of the PR ligands tested inhibit cell growth [23]. In order to determine whether the levels or phosphorylation state of PR are reflected in the growth patterns of T47D cells, we monitored the effects of these PR ligands on the immunoblotted PR band intensities, the relative intensities, of PR-A and PR-B, and their phosphorylation states that are reflected in their altered mobility during SDS-PAGE. Under conditions where the PR ligands inhibit cell proliferation, each ligand had distinctively different qualitative and quantitative effects on PR. Short term treatment of the cells with R5020 or RU486 induced a characteristic phosphorylation-dependent upshift of both PR-A and PR-B. The phosphorylated PR was stable for up to 4 days after treatment of the cells with RU486, but was down regulated between 6-24 h after treatment with R5020. No replenishment of PR in cells treated with R5020 was detected. ZK98299, at concentrations tested, had no qualitative or quantitative effects on PR. Culturing cells for 8 days in medium containing steroid-depleted serum caused a significant reduction in the PR band intensity without causing a change in the ratio of PR-A and PR-B or their phosphorylation states. This decrease in the PR band intensity was reversed by maintaining the cells in 1 nM estrogen, but was potentiated by RU486 or ZK98299. These observations support the view that decreased PR levels may play a role in the stimulatory effects of R5020 and RU486 when cells are cultured under non-estrogenized conditions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006982528297
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  • 28
    Electronic Resource
    Electronic Resource
    Effects of antiprogestins on the rate of proliferation of breast cancer cells (1999)
    Springer
    Molecular and cellular biochemistry 198 (1999), S. 141-149 
    Details
    ISSN: 1573-4919
    Keywords: T47D cells ; breast cancer ; cellular proliferation ; progesterone ; estradiol ; steroid receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract We have examined the influence of progestins (progesterone, R5020) and antiprogestins (RU486, ZK98299, Org 31710 and Org 31806) on the rate of proliferation of wild type T47D cells cultured in whole fetal bovine serum (FBS) or in single charcoal stripped fetal bovine serum (SSFBS). All of the progesterone antagonists RU486, ZK98299 and two novel antiprogestins Org 31710 and Org 31806 inhibited cell proliferation when cells were cultured in FBS. In contrast, all of the antiprogestins with the exception of ZK98299 enhanced cell growth when cells were cultured in SSFBS. This stimulatory effect of RU486 was observed only at a high concentration of the ligand (1 μM). The effect of R5020, however, was concentration independent. The number of cells in the presence of RU486 was ~ 600% followed by R5020 ~ 400% above control values after a 28 day culturing period. In contrast, when the cells were grown in the presence of medium containing non-stripped whole serum, RU486 inhibited the extent of cell proliferation by 45%. Estradiol (E2) stimulated the rate of proliferation in cells cultured in SSFBS. Similar to when cells were cultured in whole serum, the antiprogestins inhibited cell growth in E2-supplemented SSFBS. Detection of the growth enhancement effects of progesterone receptor (PR) ligands such as RU486 and R5020 on the cells grown in charcoal-stripped medium appear to require the removal of E2 by charcoal stripping of the serum.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006945813508
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  • 29
    Electronic Resource
    Electronic Resource
    Toward Checkmate: Biology and Breast Cancer Therapy for the New Millennium (1999)
    Springer
    Investigational new drugs 17 (1999), S. 417-427 
    Details
    ISSN: 1573-0646
    Keywords: breast cancer ; growth factors ; metalloproteinase ; angiogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract A better understanding of the biology of breast cancer should leadto the rational development of new treatments and the ability tocustomize therapy for individual patients. Though promising intheory, translating advances in biological knowledge to the clinichas been difficult. Recently several areas of research haveproduced treatments which have entered clinical trials; three willbe reviewed here. The growth of breast cancer is regulated bygrowth factors and their receptors; amplification or overexpressionis associated with poor prognosis. As such inhibition of growthfactors and/or growth factor receptors may provide an idealtherapeutic target. Herceptin binds to c-erbB-2, a member of theepidermal growth factor receptor family. Significant responses wereseen in patients with c-erbB-2 overexpressing breast cancer withHerceptin administered as a single agent or in combination withchemotherapy. Herceptin was approved by the Food and DrugAdministration in late 1998. Breast cancer invasion and metastasisrequires degradation of the surrounding basement membrane by matrixmetalloproteinases and other proteolytic enzymes. Syntheticinhibitors of these enzymes are now in clinical trials. Breastcancers must stimulate angiogenesis, the growth of new bloodvessels, in order to grow beyond a few millimeters in diameter.This nascent vascular network provides another opportunity fortherapy. Preclinical models support the critical role ofangiogenesis and the therapeutic benefit of angiogenesisinhibition; clinical trials are underway.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006311227965
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  • 30
    Electronic Resource
    Electronic Resource
    Evaluation of seprase activity (1999)
    Springer
    Clinical & experimental metastasis 17 (1999), S. 67-72 
    Details
    ISSN: 1573-7276
    Keywords: breast cancer ; extracellular matrix ; gelatinase ; invasion ; matrix metalloproteinase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Seprase is a serine protease that is integral to the plasma membrane and is overexpressed by invasive tumor cells (Piñeiro-Sánchez et al., J Biol Chem 1997; 272: 7595–601; Monsky et al., Cancer Res 1994; 54: 5702–10). Seprase activity is most often assessed by zymography, which is not a quantitative assay. This study establishes a relatively simple and quantitative method for determining seprase activity. The degradation of a 3H-gelatin substrate is measured in the presence of 5 mM EDTA which inhibits matrix metalloproteinases but not seprase. The quantitative character of the assay was demonstrated using partially purified seprase from chicken embryos, a preparation that lacks detectable matrix metalloproteinase activity. In this assay, release of 3H-gelatin fragments is linear over time for 1.5 μg/assay seprase concentration as well as for preparations concentrated or diluted by five fold (7.5 μg/assay and 0.3 μg/assay respectively). Additional experiments were performed to validate the quantification of seprase activity using the radiographic assay by comparing the results to zymography. Exposure to 22 or 37 °C results in maximal seprase activity while exposure to 80 or 100 °C completely abolishes seprase activity in both zymography and the radiographic assay. Exposure to 60 °C abolished seprase activity as judged by zymography, but about 50% gelatinase activity was observed using the 3H-gelatin substrate. Immunopreciptiation with seprase-specific antibody specifically removed seprase and lowered the seprase activity remaining in the extracts as judged by both assays. Investigation of the seprase that was partially purified from human breast cancer tissue revealed that its specific activity (cpm gelatin fragments released/ {mg protein×h}) is five times greater than that of seprase purified from chicken embryos. This assay will be useful for determining the seprase activity in extracts of tumor tissues and cells as well as for identifying inhibitors of seprase.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026430206274
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  • 31
    Electronic Resource
    Electronic Resource
    Loss of heterozygosity in BRCA1 and BRCA2 markers and high‐grade malignancy in breast cancer (1999)
    Springer
    Breast cancer research and treatment 53 (1999), S. 9-17 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; microsatellites ; prognostic factors ; 17q21 region ; 13q12‐13 region
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Loss of heterozygosity (LOH) in loci of the 17q21 and 13q12‐13 regions can collaborate in the inactivation of BRCA1, BRCA2, and possibly other genes implicated in the pathogenesis of breast carcinomas. We investigate allelic losses in microsatellites of the BRCA1 and BRCA2 regions, and their correlations with seven pathologic parameters in 140 breast carcinomas. Those cases showing LOH in the region of the RB gene, 13q14, were excluded from the study. The LOH analysis was performed by amplifying DNA by PCR, using four markers of the 17q21 region (D17S856, D17S855, D17S1323, and D17S1327) and four markers of the 13q12‐13 region (D13S290, D13S260, D13S310, and D13S267). LOH in the BRCA1 region was found in 47% of tumors, correlating significantly with estrogen receptor content (p = 0.025), progesterone receptors (p = 0.004), higher grade (p = 0.0008), peritumoral vessel invasion (p = 0.001), and lymph node metastases (p = 0.002). When we excluded the cases with LOH in the BRCA2 region and those not informative for it, the significance disappeared. In the BRCA2 region, a rate of LOH of 51% was found; it correlated significantly with estrogen receptor content (p = 0.002), progesterone receptors (p =0.03), peritumoral vessel invasion (p = 0.005), higher grade (p =0.002), and lymph node metastases (p = 0.001). When cases with BRCA1 losses and those not informative were excluded, again the significance disappeared. Concomitant losses in the BRCA1 and BRCA2 regions were found in 32% of cases, correlating significantly with lymph node metastases (p = 0.0002), estrogen receptor content (p = 0.003), progesterone receptors (p = 0.001), histologic grade (p =0.01), and peritumoral vessel invasion (p = 0.0004). These results suggest that concomitant losses in both regions could have a functional effect, influencing the presence of a poor tumor pathophenotype in breast carcinomas.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006082117266
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  • 32
    Electronic Resource
    Electronic Resource
    Quantitative changes in cytological molecular markers during primary medical treatment of breast cancer: A pilot study (1999)
    Springer
    Breast cancer research and treatment 53 (1999), S. 51-59 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; neoadjuvant therapy ; FNA ; estrogen receptor ; progesterone receptor ; p53 ; Bcl‐2 ; Ki67 ; SPF ; ploidy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aim: To quantify the changes in biological molecular markers during primary medical treatment in patients with operable breast cancer and to assess their possible relationship with response to treatment. Methods: The treatment group consisted of 31 patients with operable breast carcinomas, median age 57 years (range 41–67), treated with four 3‐weekly cycles of chemotherapy with Mitoxantrone, methotrexate (± mitomycin C), and tamoxifen before surgery. Fine needle aspiration (FNA) was used to obtain samples from patients prior to and at 10 or 21 days post‐treatment. The following molecular markers were assessed: estrogen receptor (ER), progesterone receptor (PgR), p53, Bcl‐2, and Ki67 measured by immunocytochemistry, and ploidy and S‐phase fraction (SPF) by flow cytometry. To evaluate the reproducibility of the technique, repeat FNA was performed in a separate non‐treatment control group of 20 patients and the same molecular markers assessed, two weeks after the first sample with no intervening treatment. Results: The non‐treatment control group showed a high reproducibility for the measurement of molecular markers from repeat FNA. In the treatment group there was a non‐significant reduction in SPF and a significant reduction (p = 0.005) in Ki67. Patients who responded to neoadjuvant therapy were more likely to have a reduction in these two markers than those who failed to respond. Similarly, a reduction in ER scores was observed between the first and second samples (p = 0.04). For PgR, the change between the first and second samples was not significant although there was a significant difference between responders and non‐responders (p = 0.03). All nine patients with an increase in PgR were responders. No significant changes in p53 or Bcl‐2 were observed during treatment. Conclusion: Molecular markers can be adequately measured from FNA samples prior to and during neoadjuvant therapy. Changes in cellular proliferation and hormone receptors have been shown that may be related to tumour response. These relationships should be assessed in a larger cohort of patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006179511178
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  • 33
    Electronic Resource
    Electronic Resource
    Human papillomavirus 16 in breast cancer of women treated for high grade cervical intraepithelial neoplasia (CIN III). (1999)
    Springer
    Breast cancer research and treatment 53 (1999), S. 121-135 
    Details
    ISSN: 1573-7217
    Keywords: HPV 16 ; breast cancer ; CIN III ; PCR ; southern blot ; in situ hybridization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Women with both a history of high grade cervical intraepithelial neoplasia (CIN III) and breast carcinoma as second primary cancer were selected for studying the presence of HPV in breast carcinomas. Paraffin embedded material from 38 patients with 41 breast carcinoma cases after CIN III were examined by polymerase chain reaction (PCR) and in situ hybridization. By PCR we detected HPV 16 DNA in 19 out of 41 cases (46%) of the breast carcinomas. One case proved to be HPV 16 positive also by in situ hybridization. HPV 16 was also detected in 32 out of the 38 patients with CIN III (84%). All HPV 16 positive breast carcinomas were HPV 16 positive in their corresponding CIN III lesions. Eight patients with diagnosed breast cancer before the CIN III lesions were used as controls. None of these had HPV positive breast carcinomas. No cases were positive for HPV 11, 18, or 33. HPV 16 was detected in the primary tumours, in local metastases from HPV 16 positive tumours, in a distant HPV 16 positive breast carcinoma metastasis to the colon, and in other primary cancers in patients with HPV 16 positive breast carcinomas and HPV 16 positive CIN III. Estrogen and progesterone receptors were quantified in the HPV positive and HPV negative breast carcinomas, and there was no significant difference in the fraction positive in the two groups. Oncogenic HPV DNA might be transported from an original site of infection to other organs by blood or lymph, and possibly be a factor in the development of cancer in different organs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006162609420
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  • 34
    Electronic Resource
    Electronic Resource
    Genetic anticipation and breast cancer: a prospective follow‐up study (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 21-28 
    Details
    ISSN: 1573-7217
    Keywords: age of diagnosis ; ascertainment ; breast cancer ; genetic anticipation ; prospective cohort family study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Genetic anticipation is characterized by an earlier age of disease onset, increased severity, and a greater proportion of affected individuals in succeeding generations. The discovery of trinucleotide repeat expansion (TRE) mutations as the molecular correlate of anticipation in a number of rare Mendelian neurodegenerative disorders has led to a resurgence of interest in this phenomenon. Because of the difficulties presented to traditional genetics by complex diseases, the testing for genetic anticipation coupled with TRE detection has been proposed as a strategy for expediting the identification of susceptibility genes for complex disorders. In the case of breast cancer, a number of previous studies found evidence consistent with genetic anticipation. It is known that a proportion of such families are linked to either BRCA1 or BRCA2, but no TRE mutations have been identified. It has been shown that the typical ascertainment employed in studies purporting to demonstrate genetic anticipation combined with unadjusted statistical analysis can dramatically elevate the type I error. We re‐examine the evidence for anticipation in breast cancer by applying a new statistical approach that appears to have validity in the analysis of anticipation to data ascertained from a recent follow‐up of a large prospective cohort family study of breast cancer. Using this approach, we find no statistically significant evidence for genetic anticipation in familial breast cancer. We discuss the limitations of our analysis, including the problem of adequate sample size for this new statistical test.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006151132592
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  • 35
    Electronic Resource
    Electronic Resource
    Differential regulation of normal and tumoral breast epithelial cell growth by fibroblasts and 1,25‐dihydroxyvitamin D3 (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 29-39 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; cell interactions ; 1,25‐dihydroxyvitamin D3 ; fibroblast ; normal epithelial cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Mesenchymal‐epithelial interactions are of paramount importance during normal and tumoral breast developments. We have investigated the paracrine growth regulation of normal and tumoral breast epithelial cells by fibroblasts derived from normal or pathological breast tissues. In some cases, breast cancer MCF‐7 cells or normal epithelial cells in primary culture were cocultured with fibroblasts in a Transwell system allowing diffusible factor exchanges. Alternatively, conditioned medium produced by fibroblast cultures was added to epithelial cell cultures. Fibroblasts were shown to stimulate the proliferation of normal and carcinoma cells through paracrine mechanisms. However, the paracrine exchanges appeared to be different in normal versus tumoral breast epithelial cell growth regulation. Moreover, vitamin D‐related compounds that have been proposed as anti‐tumoral drugs were studied for their ability to affect normal and tumoral mammary epithelial cell proliferation and to interfere with the growth‐regulatory activity of fibroblasts. Whereas vitamin D compounds inhibited MCF‐7 cell growth, they led to a marked stimulation of the proliferation of normal mammary epithelial cells. Moreover, it was shown that the vitamin D analog EB 1089 can block the mitogenic effect of fibroblast‐conditioned medium on tumoral but not normal breast epithelial cells. The differential effects of vitamin D compounds on cell proliferation provide further data in favor of the different behaviours of normal and tumoral mammary epithelial cells. The potential therapeutic use of vitamin D derivatives in the treatment of breast cancer is supported by these results but their growth‐stimulatory properties on normal epithelial cells cannot be overlooked.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006163418479
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  • 36
    Electronic Resource
    Electronic Resource
    Regulation of BAX and BCL‐2 expression in breast cancer cells by chemotherapy (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 107-117 
    Details
    ISSN: 1573-7217
    Keywords: apoptosis ; Bax ; Bcl‐2 ; breast cancer ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Optimizing chemotherapeutic drug delivery strategies relies, in part, on identification of the most clinically effective sequence, dose, and duration of drug exposure. The combination of dose intensive etoposide (VP‐16) followed by cyclophosphamide has clinical efficacy in the treatment of advanced breast cancer. However, molecular mechanisms that underlie the effectiveness of this combination of chemotherapeutic agents have not been investigated. In this study we investigated regulation of BAX and BCL‐2 expression by VP‐16 and cyclophosphamide as a potential mechanism for the induction of breast cancer cell death induced by this regimen. There was a dose and time dependent increase in BAX expression in the breast cancer cell lines MCF‐7, MDA‐MB‐435S, and MDA‐MB‐A231 following in vitro treatment with 50–100 μM VP‐16. Elevation of BAX protein expression in the presence of VP‐16 alone did not correlate with reduced viability or induction of apoptosis in MCF‐7, MDA‐MB‐435S, or MDA‐MB‐A231. VP‐16 did effectively block the breast cancer cell lines evaluated (MCF‐7 and MDA‐MB‐435S) at G2/M phase of the cell cycle, confirming activity of the drug in vitro. MCF‐7 and MDA‐MB‐435S cells that were pre‐treated with VP‐16 and subsequently exposed to 1.0–12.0 μg/m1 4‐hydroperoxycyclophosphamide (4HC), an active metabolite of cyclophosphamide, had markedly reduced viability when compared to matched controls treated with either VP‐16 or 4HC individually. Consistent with this loss of viability, exposure of all three cell lines to the combination of VP‐16 and 4HC resulted in higher BAX protein levels than those observed following treatment with either single agent. This combination of chemotherapeutic agents also resulted in reduced BCL‐2 expression. These observations suggest that combination chemotherapy may derive its efficacy, in part, through coordinated regulation of specific gene products associated with apoptosis. Characterization of molecular events that underlie susceptibility of specific tumor cells to combination chemotherapeutic regimens may lead to additional improvements in treatment strategies for this disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006175811676
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  • 37
    Electronic Resource
    Electronic Resource
    Cathepsin D expression by cancer and stromal cells in breast cancer: an immunohistochemical study of 1348 cases (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 135-145 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; cathepsin D ; immunohistochemistry ; protease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study was aimed at investigating the influence of cathepsin D (CD) expression by cancer cells and stromal cells on breast cancer prognosis. This is a study of 1348 node‐positive (NPBC) and node‐negative (NNBC) breast cancers diagnosed between 1980 and 1986 and with a minimum follow‐up of 5.2 years. CD expression was assessed by immunohistochemistry on archival material using a polyclonal antibody. The expression by cancer and stromal cells was assessed separately and correlated with distant metastasis free (DMFS) and overall survival (OS). Cancer cells expressed CD (more than 10% cells expressing CD) in 38.9% of cases and reactive stromal cells in 43.6%. CD expression by reactive stromal cells, and not cancer cells, correlated with several factors of poor prognosis by cancer cells. A strong association was also found with expression of other proteases (stromelysin‐3, gelatinase A, and urokinase Plasminogen Activator) by these same reactive stromal cells. CD expression by cancer cells did not predict DMFS or OS but, by univariate analysis, CD expression by reactive stromal cells was associated with earlier recurrence and shorter survival in NNBC (p = 0.0425) and NPBC patients submitted to adjuvant chemotherapy (p = 0.0234). However, CD expression by reactive stromal cells remained a significant predictor of recurrence by multivariate analyses only in a subgroup of NPBC submitted to adjuvant chemotherapy. Overall, those data support the concept that proteases produced by reactive stromal cells are under cancer cell stimulation and that CD by stromal cells, and not cancer cells, influences the prognosis, but only in a subgroup of patients with breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006140213493
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  • 38
    Electronic Resource
    Electronic Resource
    Assessment of quality of life in women undergoing hormonal therapy for breast cancer: validation of an endocrine symptom subscale for the FACT‐B (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 187-197 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; endocrine therapy ; FACT‐B ; FACT‐ES ; quality of life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Existing quality of life instruments do not include adequate items to measure the side effects and putative benefits of hormonal treatments given in breast cancer. We report the development and validation of an 18 item endocrine subscale (ES) to accompany a standardised breast cancer quality of life measure, the Functional Assessment of Cancer Therapy (FACT‐B) [1]. The FACT‐ES (FACT‐B plus ES) was tested initially on 268 women with breast cancer receiving endocrine treatments. Alpha coefficients for all subscales demonstrated good internal consistency (range α = 0.65–0.87). Test‐retest reliability of the ES indicated good stability (r = 0.93, p 〈 0.001). Advanced breast cancer patients' quality of life was high, showing the efficacy of endocrine therapy, but women with primary disease reported better physical, social, and functional well‐being and fewer breast cancer concerns. Most frequently reported symptoms were loss of sexual interest (31%), weight gain (25%), and hot flushes (24%). Significant differences were found between treatment groups for hot flushes and vaginal dryness. Two assessments of the instrument's responsiveness to change were made; 32 women in a clinical trial of endocrine therapy and 18 women without breast cancer taking HRT completed the FACT‐ES at baseline, 4, 8, and 12 weeks. Trial patients reported significantly more symptoms at 8 and 12 weeks than at baseline. Women taking HRT reported significantly fewer or less severe symptoms than at baseline. In conclusion the FACT‐ES has acceptable validity and reliability and is sensitive to clinically significant change, making it suitable for clinical trials of endocrine therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006263818115
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  • 39
    Electronic Resource
    Electronic Resource
    Induction of insulin‐like growth factor binding protein expression by ICI 182,780 in a tamoxifen‐resistant human breast cancer cell line (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 231-242 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; ICI 182 ; 780 ; IGFBPs ; tamoxifen resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Earlier studies in our laboratory demonstrated that the steroidal antiestrogen ICI 182,780 is very effective in abolishing the tamoxifen‐resistant proliferation of MCF 7/5‐23 cells [1]. In addition, preliminary binding studies showed that ICI 182,780 increased the binding of insulin‐like growth factor (IGF)‐I to the MCF 7/5‐23 cells, although this finding was not the result of an increase in the expression of the insulin‐like growth factor‐I receptor (IGF‐IR). Hence, we reasoned that the inhibition of tamoxifen‐resistant cell growth by ICI 182,780 might have been due to increased expression of insulin‐like growth factor binding proteins (IGFBPs). We observed the up‐regulation of non‐insulin‐suppressible IGF‐I binding in both the tamoxifen‐sensitive MCF 7/5‐21 cell line (1.5‐fold) and the tamoxifen‐resistant MCF 7/5‐23 cell line (2.5‐fold) after 5 days of treatment with ICI 182,780 (10−7 M) in serum‐free medium, suggesting a role for cell‐associated IGFBPs. Affinity cross‐linking experiments confirmed the presence of an IGF‐I:IGFBP complex of approximately 38‐kDa in tamoxifen or ICI 182,780‐treated cells. Western ligand blots showed higher levels of a soluble 30‐kDa IGFBP in media conditioned by either of the subclones that had been treated with ICI 182,780, an effect consistently opposed by estrogen (E2:10−9 M). RT‐PCR showed higher levels of IGFBP‐5 mRNA than any of the other known IGFBPs, suggesting that this was the major IGFBP subtype. The protein was subsequently identified by Western immunoblotting as IGFBP‐5. In conclusion, we postulate that this may be a mechanism contributing to the greater potency of ICI 182,780 in the growth inhibition of the MCF 7/5‐23, tamoxifen‐resistant cell line.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006274712664
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  • 40
    Electronic Resource
    Electronic Resource
    A study on the cost effectiveness of sestamibi scintimammography for screening women with dense breasts for breast cancer (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 243-258 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; cost effectiveness ; dense breasts ; mammographic parenchymal patterns ; Sestamibi scintimammography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The potential impact of Sestamibi scintimammography (SSMM) on the cost effective management of women with dense breasts is not known. This study addresses this issue quantitatively by examining the impact of SSMM based screening strategies on the ∼3,000,000 women over 40 with very dense breasts (DY patterns) without palpable masses and who have had one or more prior mammograms, who undergo routine screening each year. Quantitative decision tree sensitivity analysis was used to compare the conventional mammography (MM) strategy (strategy A), which does not subject patients with negative mammograms to any further examination until their next screening, with two decision strategies for screening with SSMM SSMM after a negative mammogram (strategy B) or SSMM as the only screening test for women already identified as having dense breasts by a previous mammogram (strategy C). Cost effectiveness was measured by calculating the incremental cost effectiveness ratio (ICER) of strategies B and C, which is the cost of achieving an additional year of life in the screening population by choosing a SSMM based decision strategy rather than the conventional strategy. Strategies B and C reduced the number of false negative diagnoses by 62% and 8%, respectively. The ICER was $632,000 and $3.18M per life year for strategy B and C, respectively. To be cost effective, the pre‐test probability of cancer in the study population must be greater than 3% for strategy B or the cost of SSMM must be less than $50 for strategy C. These results show the ICER of an SSMM based breast cancer screening strategy in the management of patients with dense breasts is not currently within the range (∼$50,000 per year life saved) of other commonly performed medical interventions that are considered cost effective.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006211817207
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  • 41
    Electronic Resource
    Electronic Resource
    Vorozole results in greater oestrogen suppression than formestane in postmenopausal women and when added to goserelin in premenopausal women with advanced breast cancer (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 25-34 
    Details
    ISSN: 1573-7217
    Keywords: aromatase inhibition ; breast cancer ; formestane ; GnRH agonist ; goserelin ; pharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The high potency and selectivity of new aromatase inhibitors has translated to greater efficacy and improved tolerability in comparison with established second‐line hormonal agents for advanced breast cancer in phase III clinical trials. Two pharmacological studies are reported which assess the use of one of these inhibitors, vorozole, in combination or comparison with well‐established methods of oestrogen deprivation in pre and postmenopausal patients. When combined with the gonadotrophin‐releasing hormone agonist (GnRHa) goserelin in 10 premenopausal patients, vorozole markedly enhanced the suppression of serum levels of oestrone, oestradiol and, oestrone sulphate beyond that achieved by goserelin alone (by a mean 74%, 83%, and 89%, respectively). The combination was well‐tolerated and had no significant effects on androgen levels. Vorozole was compared with formestane in 13 postmenopausal women and serum oestrone, oestradiol, and oestrone sulphate levels were suppressed by 47%, 30%, and 70%, respectively, more by vorozole than by the steroidal aromatase inhibitor. Again the tolerability was excellent. The plasma oestrogen levels in the postmenopausal patients on vorozole were lower than in the premenopausal patients on goserelin plus vorozole, indicating that ovarian oestrogen synthesis may be relatively resistant to aromatase inhibition, even during GnRHa treatment. Thus, in both pre and postmenopausal patients substantially greater suppression of oestrogen can be achieved by vorozole compared with alternative approaches. Existing clinical–pharmacological correlates suggest that these increases in pharmacological effectiveness may result in enhanced clinical effectiveness.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006289811540
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  • 42
    Electronic Resource
    Electronic Resource
    Hsp27 overexpression inhibits doxorubicin–induced apoptosis in human breast cancer cells (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 185-194 
    Details
    ISSN: 1573-7217
    Keywords: apoptosis ; breast cancer ; doxorubicin ; hsp27 ; topoisomerase II
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previously we demonstrated that heat shock protein 27 (hsp27) overexpression confers resistance to the chemotherapeutic agent doxorubicin in MDA–MB–231 breast cancer cells. Since induction of apoptosis is one underlying mechanism of chemotherapeutic drug action, we investigated the effect of hsp27 overexpression on doxorubicin–induced apoptosis, finding that hsp27 protects MDA–MB–231 cells from apoptosis. We also examined expression of the doxorubicin target, topoisomerase II (topo II), in control and hsp27–overexpressing stable transfectants, as topo II expression is important for both drug sensitivity and the initiation of apoptosis by doxorubicin. The relative levels of both topo IIα and β were higher in the controls than the hsp27–overexpressing clones, suggesting that the apoptotic protective effect of hsp27 overexpression in MDA–MB–231 cells is associated with altered topo II expression.abstract
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006207009260
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  • 43
    Electronic Resource
    Electronic Resource
    pS2 (TFF1) levels in human breast cancer tumor samples: correlation with clinical and histological prognostic markers (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 251-263 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; mRNA ; pS2 ; prognostic marker ; RT–PCR ; TFF1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The expression of pS2 (TFF1) has been previously shown to identify patients with improved response to anti–hormonal therapy and more favorable outcome. In the current study, 100 human breast carcinoma samples obtained from the Manitoba Breast Tumor Bank were analyzed for pS2 mRNA using a quantitative, competitive reverse transcriptase–polymerase chain reaction (qcRT–PCR) assay. A pS2/ß–actin cut–off criterion of 0.010 was established to classify tumors as either pS2 positive or pS2 negative. pS2 mRNA levels were positively associated with both ER and PR, with the majority of ER+ (59) and PR+ (60) tumors also being positive for pS2. In addition, a significant linear correlation was observed between the amount of pS2 mRNA and ER (p〈0.0001) and PR (p〈0.0001) protein. pS2 mRNA levels also exhibited an inverse association with tumor size and histological grade, consistent with the observation that pS2 is primarily expressed in small (T 〈 2.0 cm), but well differentiated tumors (Grades I and II). No associations were observed with tumor cell type, patient age, or lymph node status. The strong correlation displayed between pS2 and a number of currently used breast cancer prognostic markers supports the clinical use of pS2 to further assess tumor status and patient outcome.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006215310169
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  • 44
    Electronic Resource
    Electronic Resource
    Synergistic action of apoptosis induced by eicosapentaenoic acid and TNP‐470 on human breast cancer cells (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 147-158 
    Details
    ISSN: 1573-7217
    Keywords: angiogenesis inhibitor ; apoptosis ; Bcl‐2 ; breast cancer ; eicosapentaenoic acid ; TNP‐470
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of eicosapentaenoic acid (EPA) and an angiogenesis inhibitor (TNP‐470) on the suppression of breast cancer cell growth were examined in five human breast cancer cell lines (MDA‐MB‐231, T‐47D, MCF‐7, KPL‐1, and MKL‐F). In all five cell lines, EPA and TNP‐470 alone both showed tumor growth inhibition in a time‐ and dose‐dependent manner, and in combination, a synergistic effect was seen at high concentrations. EPA plus TNP‐470 treatment evoked apoptosis as confirmed by the appearance of sub G1 populations, by DNA fragmentation, and by cell morphology. With the combination, the expression of Bax and Bc1‐xS, the apoptosis‐enhancing proteins, was more up‐regulated and that of Bcl‐2 and Bcl‐xL, the apoptosis‐suppressing proteins, was more down‐regulated compared to the use of EPA or TNP‐470 alone, suggesting that their synergistic effect was due to an acceleration of apoptosis.
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    URL: http://dx.doi.org/10.1023/A:1006283131240
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  • 45
    Electronic Resource
    Electronic Resource
    Down‐regulation of gelsolin expression in human breast ductal carcinoma in situ with and without invasion (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 177-186 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; ductal carcinoma in situ (DCIS) ; gelsolin ; prognostic features
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Expression of gelsolin, an actin filament regulatory protein, in human breast ductal carcinoma in situ (DCIS) was analyzed by immunohistochemistry using a monoclonal antibody. Formalin‐fixed paraffin‐embedded tissues from 59 pure DCIS specimens and 33 DCIS specimens with associated invasive components were evaluated for gelsolin reactivity and compared to eight normal breast cases and 76 invasive breast cancers. The proportion of cases exhibiting negative/low expression of gelsolin in the epithelium was as follows – normal, 0%; pure DCIS, 56%; DCIS associated with invasion, 58% in the DCIS component and 66% in the invasive component; invasive carcinoma, 70%. These data demonstrate that down‐regulation of gelsolin expression in breast epithelium frequently parallels progression to malignancy. Testing gelsolin expression (normal vs. negative/low levels) in the DCIS lesions for associations with patient age or any of the following histopathologic parameters revealed no significant (95% probability level) correlations – tumor size; pathologic (Van Nuys system) grade; nuclear grade; necrosis; presence of histologic calcifications; presence or type of adjacent benign lesions; architectural histologic pattern; and mammographic extent. Gelsolin loss was more commonly associated with mammographic soft tissue lesions as compared to calcified lesions (P = 0.009). A positive trend of borderline significance (P = 0.06) found in the DCIS with invasion group was a correlation between down‐regulated gelsolin expression in the DCIS component and size (〈 versus ≥ 15 mm) of the invasive tumor. In conclusion, reduced gelsolin protein is detectable in at least half of breast lesions which have progressed to DCIS. The trend between increasing gelsolin loss and malignant progression from normal epithelium to DCIS to invasive breast cancer (P 〈 0.0001) suggests additional investigation is needed to determine the potential of altered gelsolin expression as a marker for prognosis and for therapeutic interventions in breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006203632228
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  • 46
    Electronic Resource
    Electronic Resource
    Anti‐human procathepsin D activation peptide antibodies inhibit breast cancer development (1999)
    Springer
    Breast cancer research and treatment 57 (1999), S. 261-269 
    Details
    ISSN: 1573-7217
    Keywords: activation peptide ; antibodies ; breast cancer ; immunotherapy ; procathepsin D
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Enzymatically inactive procathepsin D secreted from cancer cells has been confirmed to play a role in development of human breast cancer. In the present study, we focused on the role of activation peptide which was in our preliminary studies suggested to be most probably responsible for mitogenic activity of procathepsin D. Using synthetic fragments and antibodies raised against individual fragments, we demonstrated that the growth factor activity of activation peptide is localized in a nine amino acid stretch (AA 36–44) of activation peptide and moreover both anti‐activation peptide and anti‐ 27–44 peptide antibodies administered in vivo inhibited the growth of human breast tumors in athymic nude mice. Taking into account our previous results and presented data, we hypothesize that the interaction of procathepsin D activation peptide with an unknown surface receptor is mediated by a sequence 36–44 plus close vicinity. We also propose that this interaction leads in certain types of tumor derived cell lines to proliferation and higher motility. Blocking of the interaction of activation peptide by specific antibodies or antagonists might be a valuable tool in breast cancer inhibition.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006238003772
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  • 47
    Electronic Resource
    Electronic Resource
    Coexpression of c-kit and stem cell factor in breast cancer results in enhanced sensitivity to members of the EGF family of growth factors (1999)
    Springer
    Breast cancer research and treatment 58 (1999), S. 1-10 
    Details
    ISSN: 1573-7217
    Keywords: Akt ; breast cancer ; c-kit ; EGF ; ERK ; heregulin ; stem cell factor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Kit, a tyrosine kinase growth factor receptor, and its ligand, stem cell factor (SCF), are commonly coexpressed in breast cancer. We have previously shown that MCF7 cells (that naturally express SCF) transfected with a c-kit expression vector exhibit enhanced growth in serum-free medium supplemented with IGF-1. Consequently, we wished to examine the interaction of Kit/SCF with additional growth factors important in the biology of breast cancer. MCF7 transfectants expressing Kit, cultured in serum-free medium supplemented with EGF, displayed more than twice the growth of controls at identical EGF concentrations. Similar responses were seen in the presence of heregulin. The specificity of the Kit-mediated response was illustrated by a reduction in heregulin-stimulated growth in the presence of a monoclonal antibody directed against the Kit receptor. In addition, EGF- and heregulin-stimulated growth of the ZR75-1 cell line that naturally coexpresses Kit and SCF was also inhibited by the Kit blocking antibody. Preliminary investigations into the signal transduction pathways activated by these growth factors revealed that SCF activated both the Ras-MAP kinase and phosphatidyl-inositol-3-kinase (PI3 kinase) pathway. Both EGF and heregulin activated MAPK but to a lesser degree than SCF, and combination of SCF with these growth factors resulted in enhanced MAPK activation. Assessment of PI3K pathway activation using anti-phospho-Akt antibodies revealed that EGF was a poor activator of Akt; activation of this pathway was markedly enhanced by the addition of SCF. Heregulin activated Akt and addition of SCF provided no further activation. Taken together these results suggest that coexpression of SCF and Kit may enhance responsiveness to erbB ligands by enhancing activation of the MAPK and PI3K pathways.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006272527435
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  • 48
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    Electronic Resource
    Hypermethylation of the Wilms' tumor suppressor gene CpG island in human breast carcinomas (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 35-43 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; CpG island ; DNA hypermethylation ; Wilms' tumor suppressor gene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract CpG island hypermethylation is known to be associated with transcriptional silencing of tumor suppressor genes in neoplasia. We have previously detected aberrantly methylated sites in the first intron of the Wilms' tumor suppressor (WT1) gene in breast cancer. In the present study, we extended the investigation to a CpG island located in the promoter and first exon regions of WT1. Methylation of this CpG island was found to be extensive in MCF‐7 and MDA‐MB‐231 breast cancer cells, as well as in 25% (five of 20 patients) of primary breast tumors. While levels of the known 3.0‐kb WT1 mRNAs were decreased or not detected in these cell lines, the expression could be partially restored following treatment with a demethylation agent, 5‐aza‐2′‐deoxycytidine. Surprisingly, a novel 2.5‐kb WT1 transcript was expressed at high levels in both untreated and treated MDA‐MB‐231 cells. This novel transcript was likely a WT1 variant missing the first exon, and therefore escaped the methylation control present in the normal transcript. Our study implicates the future need to investigate the significance of this aberrant transcript as well as the role of WT1 CpG island hypermethylation in breast neoplasia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006222803788
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  • 49
    Electronic Resource
    Electronic Resource
    Breast cancer and timing of surgery during menstrual cycle: a 5‐year analysis of 248 premenopausal women (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 259-266 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; menstrual cycle phase ; premenopausal ; prognosis ; surgery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the present report, we retrospectively analyzed the impact of the timing of surgery during menstrual cycle on disease‐free and overall survival of 248 premenopausal patients with stage I/Il breast cancer who underwent surgery followed by anthracycline‐containing adjuvant chemotherapy. With a median follow‐up of 5 years, no statistically significant differences were observed in disease‐free or overall survival between women operated upon during the follicular (days 0–14) and the luteal (days 15–32) phase of the menstrual cycle. The impact on disease‐free and overall survival of lymph‐node status, tumor size and hormone receptor expression, but not of the phase of the menstrual cycle at the time of surgery, was confirmed by univariate and multivariate analysis. However, when combined with hormone receptor status, the phase of the menstrual cycle at the time of surgery proved useful to better define the prognosis of primary breast cancer patients, with significantly longer disease‐free and overall survival for patients operated upon during the follicular phase and with positive hormone receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006276120841
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  • 50
    Electronic Resource
    Electronic Resource
    Early age at menopause and breast cancer: are leaner women more protected? A prospective analysis of the Dutch DOM cohort (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 285-291 
    Details
    ISSN: 1573-7217
    Keywords: body mass index ; breast cancer ; menopause ; smoking
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To investigate the relationship between age at menopause, body mass index, and breast cancer risk, we used data from a prospective cohort study (DOM cohort) in the Netherlands. Participants in this breast cancer‐screening project included 10,591 women living in Utrecht, aged 49–66 years at enrolment. During a median follow‐up period of 19 years, women attended screening rounds at which anthropometric measurements were taken and questions were asked about menopausal status, age at menopause, medication use and other risk factors for breast cancer. Cox regression analysis was used to investigate the relationship between age at menopause and subsequent breast cancer risk. Breast cancer incidence decreased with an earlier age at menopause. Women with a menopausal age of 44 years or younger had a 34% lower risk of breast cancer, than women with a menopausal age over 54 years (hazard ratio is 0.66 (95% confidence interval 0.43–0.91)). The annual hazard of breast cancer incidence decreased by 2.6% per year reduction in age at menopause. The protective effect of an early age at menopause was stronger for women with a low body mass index (≤27 kg/m2; reduction of 44%) than for women with a high body mass index (〉27 kg/m2; reduction of 24%), although this difference was not statistically significant (P for interaction = 0.58). This difference was most pronounced in women who had ever smoked. Adjustment for known breast cancer risk factors did not alter the crude risk estimates significantly. In conclusion, this study provides evidence of the protective effect of lower age at menopause on subsequent breast cancer risk. This protective effect may be even stronger in leaner women.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006277207963
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  • 51
    Electronic Resource
    Electronic Resource
    Suppression of parathyroid hormone‐related protein messenger RNA expression by medroxyprogesterone acetate in breast cancer tissues (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 11-23 
    Details
    ISSN: 1573-7217
    Keywords: androgen receptor ; bone metastasis ; breast cancer ; medroxyprogesterone acetate ; parathyroid hormone‐related protein ; progesterone receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The level of parathyroid hormone‐related protein (PTHrP) expressed in breast cancer tissue is closely related to the incidence of bone metastasis. We examined the PTHrP mRNA expression in breast cancer tissues by coamplification polymerase chain reaction (PCR) in mole ratio to internal standard β‐actin mRNA. The PTHrP expression was higher in premenopausal patients than in postmenopausal patients (P〈0.05). More pronounced difference by menopause found in estrogen receptor (ER) positive groups (P〈0.001) indicated that the PTHrP expression in breast cancer tissue is hormonally regulated and might be altered by endocrine agents. To clarify the changes of PTHrP expression by endocrine therapy of breast cancer, we measured PTHrP expression in the breast cancer tissue incubated for 24 h with 1 × 10−8 M of estradiol (E2), 1 × 10−6 M of tamoxifen (TAM) and 1 × 10−5 M of medroxyprogesterone acetate (MPA). The PTHrP expression was decreased significantly by MPA (P〈0.005), while E2 and TAM did not change the PTHrP expression. Progesterone receptor (PgR) mRNA expression was also examined to confirm that the breast cancer tissue responds to E2 and TAM. The results were well compatible with the better therapeutic effect of MPA reported for the treatment of breast cancer with bone metastases. As a potential candidate for the receptor that mediates the suppressive effect of MPA, androgen receptor (AR) is suggested most probable. Present results also demonstrated that the clinical response of individual tumors is closely associated with the early in vitro changes of gene expression detected in the cancer specimen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006254006088
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  • 52
    Electronic Resource
    Electronic Resource
    Quality of life in the first year after breast cancer surgery: rehabilitation needs and patterns of recovery (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 45-57 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; psychological distress ; quality of life ; rehabilitation needs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. Although mortality rates from breast cancer are declining, many breast cancer survivors will experience physical and psychological sequelae that affect their everyday lives. Few prospective studies have examined the rehabilitation needs of newly diagnosed breast cancer patients, and little is known about the predictors of health‐related quality of life (QOL) in this population. Methods. Between 1987 and 1990, 227 women with early stage breast cancer participated in a prospective longitudinal study in which detailed information was collected through interviews, standardized measures of QOL and psychological distress, and clinical evaluation. Comparisons of physical and treatment‐related problems were made according to type of surgical treatment. Multivariate regression analysis was performed to examine the predictors of QOL at one year after surgery. Results. Physical and treatment‐related problems were reported frequently one month after breast cancer surgery, and occurred with equal frequency in women receiving modified radical mastectomy or breast conservation treatment. There were no significant differences in problems reported at one year by type of surgery; however, frequently reported problems include ‘numbness in the chest wall or axilla,’ ‘tightness, pulling or stretching in the arm or axilla,’ ‘less energy or fatigue,’ ‘difficulty in sleeping,’ and ‘hot flashes’. There was no relationship between the type of surgery and mood or QOL. Poorer QOL one year after surgery was significantly associated with greater mood disturbance and body image discomfort one month after surgery, as well as positive lymph node involvement. Although the majority of patients experienced substantial disruptions in the physical and psychosocial dimensions of QOL post‐operatively, most women recovered during the year after surgery, with only a minority (〈10%) significantly worsening during that time. Conclusions. At one year after surgery, most women report high levels of functioning and QOL, with no relationship between the type of surgery and QOL. Women who reported lower levels of QOL at one year after diagnosis had greater mood disturbance and poorer body image one month after surgery, as well as lower income and positive axillary nodes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006214830854
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  • 53
    Electronic Resource
    Electronic Resource
    Postoperative chemo–endocrine treatment with mitomycin C, tamoxifen, and UFT is effective for patients with premenopausal estrogen receptor–positive stage II breast cancer (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 111-122 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; estrogen receptor ; mitomycin C ; postoperative chemotherapy ; tamoxifen ; UFT
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effectiveness of combining mitomycin C (MMC), tamoxifen (TAM), and 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) was evident in patients with estrogen receptor-positive (ER+) breast cancers. UFT, an oral preparation of tegafur and uracil at a molar ratio of 1:4, was reported to have higher antitumor effects than tegafur alone for patients with breast cancer. Therefore, the combined chemotherapy of MMC, TAM and UFT may possibly be effective for breast cancer. From 1988 to 1991, we studied the effects of postoperative adjuvant therapy for Japanese women with stage II breast cancer, all seen at 71 institutions in western areas of Japan. Five hundred and ninety four patients with stage II primary breast cancer who had undergone curative surgery, including total mastectomy and axillary lymph node dissection, were enrolled. On the day of surgery, each patient was given 13 mg/m2 of MMC intravenously. Patients with ER+ tumors were then assigned to group A or group B. Group A received 30 mg/day of TAM given orally from postoperative 2 weeks, for 2 years. Group B was additionally given an oral dose of 300 mg/day of UFT for 2 years, given concomitantly with 30 mg/day of TAM. Patients with ER− tumors were assigned to group C or group D. Group C were prescribed 300 mg/day of UFT, orally, from postoperative 2 weeks for 2 years, and group D were additionally given an oral dose of 30 mg/day of TAM together with 300 mg/day of UFT. There were no differences among the groups regarding prognostic factors or doses of MMC and TAM in ER+ patients and MMC and UFT in ER− patients. Toxicity rates for leukopenia, anorexia, and nausea/vomiting were higher in group B than in group A patients. There were no statistical differences in the overall survival and disease–free survival times between groups A and B, or groups C and D, for all eligible cases. In a retrospective subgroup analysis using Bonferroni's adjustments, the additional effect of UFT on the combined treatment of MMC and TAM lengthened the disease-free survival time for patients with premenopausal ER+ cancers (corrected P value by Bonferroni's adjustments 〈0.05). Multivariate analysis showed that effects of the combined treatment of MMC, TAM, and UFT was significantly related to the menopausal status (P〈0.0 1). Our findings show that postoperative ingestion of MMC, TAM, and UFT was effective for patients with premenopausal ER+ stage II breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006221425652
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  • 54
    Electronic Resource
    Electronic Resource
    Expression of inducible nitric oxide synthase in human breast cancer depends on tumor grade (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 143-149 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; immunohistochemistry ; nitric oxide synthases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Expression of inducible nitric oxide synthase (iNOS) by tumor cells has been suggested to abrogate metastasis in several tumor models, whereas constitutive NOS expression correlated positively with tumor grade in human breast carcinoma. Whether or not expression of one of the various NOS isoforms could predict the prognosis of breast cancer, however, has not been established. In the present report we investigated the cellular distribution of NOS isoforms in a series of benign and malignant breast tumors and in normal breast tissue. Immunohistochemistry revealed that in samples of benign disease the number of iNOS + epithelial cells or total epithelial cells was 69 ± 16% (n=50). In samples of grade II invasive ductal breast carcinomas the number of iNOS+ tumor cells or total tumor cells was 62 ± 20 (n=40), compared to 12 ± 9 (n=40) in samples of grade III carcinomas (P 〈 0.0001). iNOS protein was also identifiable in most of the epithelial cells of normal breast tissue (n=4). In contrast, eNOS protein was restricted to vascular endothelial cells in all of the specimens studied. Since the presence of tumor cell iNOS protein is inversely related to the tumor’s metastatic potential, we conclude that endogenous tumor cell mediated iNOS expression might have an inhibitory effect on the metastatic process in breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006288526311
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  • 55
    Electronic Resource
    Electronic Resource
    PACAP (6–38) is a PACAP receptor antagonist for breast cancer cells (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 175-184 
    Details
    ISSN: 1573-7217
    Keywords: PACAP ; VIP ; breast cancer ; proliferation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of pituitary adenylate cyclase activating polypeptide (PACAP) analogs were investigated using breast cancer cells. 125I–PACAP–27 bound with high affinity (Kd=5 nM) to T47D cells (Bmax = 29,000 per cell). Specific 125I–PACAP–27 binding was inhibited half maximally by PACAP–27, PACAP–38, PACAP(6–38) and PACAP(28–38) with IC50 values of 8, 17, 750 and 〉3000 nM, respectively. By RT–PCR, PACAP receptor mRNA was present in MCF–7 and T47D cell lines. Polyclonal antibodies to a PACAP receptor fragment (A–8–C) were elicited. The antibodies were affinity purified, recognized a 60–kDa protein by western blot, and stained malignant cells in breast cancer biopsy specimens by immunohistochemistry. PACAP–27 elevated the cAMP in T47D cells and the increase in cAMP caused by PACAP was inhibited by PACAP(6–38). PACAP–27 stimulated c–fos mRNA in T47D cells and the increase in c-fos gene expression caused by PACAP was reversed by PACAP (6–38). PACAP (6–38) inhibited colony formation using a soft agar assay and inhibited breast cancer xenograft growth in nude mice. These data suggest that PACAP (6–38) functions as a breast cancer PACAP receptor antagonist.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006262611290
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  • 56
    Electronic Resource
    Electronic Resource
    Changes in body composition during breast cancer chemotherapy with the CMF‐regimen (1999)
    Springer
    Breast cancer research and treatment 57 (1999), S. 285-290 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; chemotherapy ; CMF ; weight gain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Weight gain is a reported problem associated with adjuvant chemotherapy for breast cancer and often generates psychosocial stress in women [1]. It also may affect prognosis and survival. Changes in body composition and weight during chemotherapy, particularly adjuvant treatment of breast carcinoma, have been previously reported [1–3]. Multiple reasons for this weight gain have been suggested though few theories have been scientifically validated [4]. The aim of this study was to investigate body composition and its relationship to weight change associated with the CMF‐based breast cancer chemotherapy protocols. Total body nitrogen (TBN), body fat, total body water (TBW), and anthropometric measurements were conducted on 25 female out‐patients (median age 47, range 26–70 years) receiving adjuvant CMF‐based chemotherapy for breast cancer. Total body nitrogen was measured using the In Vivo Neutron Capture Analysis (IVNCA) technique (on day 1 of cycles 2–6) and TBP was calculated by multiplying TBN by 6.25 [5]. Nitrogen Index (NI) was calculated by expressing TBN as a percentage of normal. There was a significant increase in mean body weight during chemotherapy of 2.35 kg (p〈0.0001). Serial measurements showed no significant change in mean TBN, NI, or percentage body fat. Break down of body weight showed a significant increase in mean TBW of 0.79 kg (p=0.003) and mean fat mass of 1.49 kg (p=0.008). We conclude that weight gain observed during adjuvant chemotherapy for breast carcinoma is primarily due to an increase in fat and TBW.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006220510597
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  • 57
    Electronic Resource
    Electronic Resource
    Involvement of nuclear steroid/thyroid/retinoid receptors and of protein kinases in the regulation of growth and of c‐erbB and retinoic acid receptor expression in MCF‐7 breast cancer cells (1999)
    Springer
    Breast cancer research and treatment 58 (1999), S. 171-181 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; c‐erbB ; cross‐talk regulation ; RAR ; retinoid ; steroid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Nuclear steroid/thyroid/retinoid receptors and c‐erbB membrane receptor tyrosine kinases control epithelial growth and differentiation. Retinoid receptors can dimerize with the vitamin D receptor, the glucocorticoid receptor or the thyroid receptor. Furthermore, multiple c‐erbB receptor dimers have been identified. It has been shown that some of these receptor pathways communicate with each other via cross‐connected regulatory networks. Molecular interactions between retinoid receptors or estrogen receptors (ER) and c‐erbB‐2, and between ER and retinoic acid receptor(RAR)‐α have been reported. Here, we demonstrate the effects of steroids/thyroids/retinoids and of activators of protein kinase A (forskolin, Forsk) and C (12‐O‐tetradecanoylphorbol‐13‐acetate, TPA), on growth and expression of c‐erbB and RARs in MCF‐7 breast cancer cells, which contain high levels of RAR‐α and ‐γ, and which express significant amounts of c‐erbB‐2 and ‐3. All trans‐retinoic acid (tRA), the anti‐estrogen ICI 182 780 (ICI), Forsk and TPA reduced, whereas triiodothyronine and 17β‐estradiol (E2) stimulated cell growth. Flow cytometry revealed that tRA and E2 reduced c‐erbB‐2 and ‐3, whereas tamoxifen, Forsk and TPA up‐regulatedc‐erbB‐2. c‐erbB‐3 was co‐regulated with c‐erbB‐2. Northern analysis demonstrated that RAR‐α was down‐regulated by dexamethasone, ICI, and TPA, whereas vitamin D3 and E2 up‐regulated RAR‐α. RAR‐γ expression was less responsive to such treatment, being reduced only by ICI and Forsk. These data indicate that nuclear receptor and protein kinase signaling communicate with each other and control the expression of RARs and c‐erbB receptors. Efficient growth control requires the coordinated interplay of both receptor systems.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006377006816
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  • 58
    Electronic Resource
    Electronic Resource
    Quantitation of erbB-2 gene copy number in breast cancer by an improved polymerase chain reaction (PCR) technique, competitively differential PCR (1999)
    Springer
    Breast cancer research and treatment 58 (1999), S. 211-215 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; gene amplification ; polymerase chain reaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A new method of measuring gene copy number in small samples of DNA was used to measure amplification of the erbB-2 gene and a reference gene in breast cancers. The method, termed 'competitively differential polymerase chain reaction' (CD-PCR), combines the advantages of two other techniques for measuring amplification by PCR, namely differential PCR (D-PCR) and competitive PCR (C-PCR). The CD-PCR methodology was evaluated for sensitivity and specificity by comparing amplification measured by CD-PCR with that obtained by fluorescence in situ hybridization (FISH), C-PCR, and Southern blotting analysis. CD-PCR analysis proved to be an accurate predictor of amplification. CD-PCR also overcomes the problems involved in variation of PCR efficiencies and DNA concentrations in tumor samples, and the problems caused by the plateau effect in PCR.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006367700783
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  • 59
    Electronic Resource
    Electronic Resource
    Influence of estrogen receptor variants on the determination of ER status in human breast cancer (1999)
    Springer
    Breast cancer research and treatment 58 (1999), S. 217-223 
    Details
    ISSN: 1573-7217
    Keywords: estrogen receptor variant mRNAs ; estrogen receptor status ; immunohistochemistry ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Determination of estrogen receptor alpha (ER) status in breast cancer is an important predictive factor for clinical response to endocrine therapy. We have recently shown that discrepancies in ER status determined by immunohistochemical assay (ER-IHA) can occur between amino-terminal (1D5) and carboxyl-terminal (AER-311) targeted ER antibodies and that those tumors which demonstrate discordance are associated with increased expression of truncated ER variant mRNAs. In this study, we have explored this observation to examine if ER variant expression can exert a direct effect on ER-IHA or whether this association is attributable to the characteristics of the antibodies. ER negative cos-1 cells were transfected with expression vectors containing wild type ER (wt-ER) and/or a frequently expressed truncated variant, ER-clone-4 variant. We found that ER-IHA performed with the same N- and C-terminal targeting ER antibodies on cos-1 cells expressing wt-ER alone demonstrated no difference in signals by western blot (P〉0.1). However, co-expression of wt-ER and the truncated ER-clone-4 variant, resulted in discordant IHA results with relatively higher ER-IHA H-scores from N-terminal antibodies (P〈0.03). Furthermore, re-examination of a subset of breast tumors previously studied by ER-IHA showed persistent concordance in 4/5 cases and persistent differences in 3/5 cases with a different pair of ER antibodies. We conclude that the presence of truncated ER variant proteins can interfere with the interpretation of ER status determined by IHA and that this may account for some of the inconsistencies between ER status and response to endocrine therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006375902601
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  • 60
    Electronic Resource
    Electronic Resource
    Occupational physical activity and risk for breast cancer in a nationwide cohort study in Sweden (1999)
    Springer
    Cancer causes & control 10 (1999), S. 423-430 
    Details
    ISSN: 1573-7225
    Keywords: breast cancer ; physical activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: Our purpose was to investigate effects of physical activity on risk for breast cancer. Methods: From the Swedish nationwide censuses in 1960 and 1970 we defined three partly overlapping cohorts of women whose occupational titles allowed reproducible classification of physical demands at work in 1960 (n=704,904), in 1970 (n=982,270), or with the same demands in both 1960 and 1970 (n=253,336). The incidence of breast cancer during 1971–89 was ascertained through record linkage to the Swedish Cancer Register. We used Poisson regression to estimate relative risks (RR). Results: A total of 20,419, 22,840, and 8261 breast cancers, respectively, were detected in the three cohorts. In all three cohorts the risk for breast cancer increased monotonically with decreasing level of occupational physical activity and with increasing socioeconomic status. Among women with the same estimated physical activity level in 1960 and 1970 the RR was 1.3 for sedentary as compared with high/very high activity level (95% CI 1.2–1.4; p for trend〈0.001). Adjustment for socioeconomic status virtually eliminated this association (RR 1.1; 95% CI 0.9–1.2; p for trend 0.12) leaving a statistically significant 30% gradient only among women aged 50–59 years at follow-up. The association between socioeconomic status and breast cancer risk was largely unchanged after adjustment for occupational physical activity. Conclusion: The protective effect of occupational physical activity on breast cancer risk, if any, appears to be confined to certain age groups.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008922205665
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  • 61
    Electronic Resource
    Electronic Resource
    Microvessel density and vascular basement membrane immunostaining in tumours of the breast (1999)
    Springer
    Angiogenesis 3 (1999), S. 175-180 
    Details
    ISSN: 1573-7209
    Keywords: angiogenesis ; breast cancer ; collagen IV ; heparan sulphate proteoglycan ; laminin ; vascular basement membrane
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There is a well established correlation between increased breast tumour microvessel density (MVD) and reduced prognosis. The aims of this study were to investigate (1) if MVD is elevated in regions other than `hotspots' of node positive versus node negative breast tumours, and (2) to quantitate the percentage of vessels without vascular basement membrane (VBM) components in high vascular density (HVD) and average vascular density (AVD) regions of node positive and node negative breast tumours. Serial sections were immunostained for CD31 and double-stained for CD31 and collagen IV (CollIV), laminin (LAM) or heparan sulphate proteoglycan (HSPG). Microvessel counts were obtained from HVD and AVD regions and the number of VBM positive vessels were expressed as a percentage of total CD31 positive vessels. MVD was significantly higher in both the HVD and AVD regions of node positive compared with node negative breast tumours (t-test; P 〈 0.03). The average percent vessels positive for CollIV, LAM or HSPG ranged from 18%–45% and did not differ between node positive and negative breast tumours (t-test; P 〉 0.05). No differences were observed in VBM immunostaining between regions of HVD and AVD (t-test; P 〉 0.05). These results demonstrate that vascular density is elevated throughout node positive breast tumours, rather than just in `hotspots', and show that there is no apparent difference in the percentage of VBM-naked vessels in node positive versus node negative breast tumours.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009035123733
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  • 62
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    Electronic Resource
    The methodology of quantitation of microvessel density and prognostic value of neovascularization associated with long‐term survival in Japanese patients with breast cancer (1999)
    Springer
    Breast cancer research and treatment 53 (1999), S. 19-31 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; long‐term survival ; microvessel density ; neovascularization ; quantitation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study updates results on methodology of quantitation of tumor neovascularization and those on the prognostic value of microvessel density (MVD) in breast cancer tissue previously published in the World J. Surg. 21: 49–56, 1997. The follow‐up period of observation of the series was extended to 20 years, and new biological indicators (i.e., proliferating cell nuclear antigen (PCNA), c‐erbB‐2, and p53) were included in the analysis. There were 109 patients with primary breast cancer, from 1971 to 1979, followed up for a median of 14 years (range, 1–20). A representative median longitudinal section of each breast tumor was immunohistochemically stained with factor VIII‐related antigen and analyzed. The three methods of identifying MVD were: (1) average microvessel count (AMC)/mm2, (2) central microvessel count (CMC)/mm2, and (3) highest microvessel count (HMC)/mm2. Thirty‐one patients (28.4%) died of breast cancer. There was a relationship between MVD and peritumor blood vessel invasion (AMC: p = 0.0114, CMC: p = 0.0319, and HMC: p = 0.0009). However, there was no relationship between MVD and other factors. Univariate analysis showed that node status (p 〈 0.0001), histological grade (p 〈 0.0001), clinical tumor size (T) (p = 0.0002), PCNA (p = 0.0033), p53 (p = 0.0043), mitotic grade (p = 0.0092), AMC (p = 0.0214), and peritumor lymphatic vessel invasion (p = 0.0467) were significantly predictive of overall survival. HMC was borderline significant (p = 0.0702), while CMC and c‐erbB‐2 were not significant. Multivariate analysis showed that T (p = 0.0005), node status (p = 0.0053), and AMC (p = 0.0485) were independent factors, but neither CMC nor HMC was independent. AMC, a significant independent prognostic factor, might be a better method than the others for evaluating angiogenesis, but further and larger studies are warranted.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006193024382
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    Prognostic factors in patients with isolated recurrences of breast cancer (stage IV-NED) (1999)
    Springer
    Breast cancer research and treatment 53 (1999), S. 105-112 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; combined modality therapy ; isolated recurrences ; radiation therapy ; surgery ; systemic therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: One to 10% of women with metastatic breast cancer have a recurrence of their disease as an isolated lesion (local, regional, or distant) which may be treated by surgical resection, irradiation, or both. These are patients with stage IV breast cancer with no evidence of disease, or stage IV-NED. Because natural history and prognostic factors for patients with stage IV-NED are poorly determined, we decided to evaluate a group of patients with stage IV-NED treated at a single institution. Patients and methods: Ninety-six patients with isolated recurrence of stage IV breast cancer were analyzed retrospectively. Treatment of loco-regional or distant recurrence was surgery in 18 patients and surgery plus irradiation in 78 patients. Seventy-nine patients received systemic therapy after loco-regional treatment (24 chemotherapy and 55 hormonotherapy). Prognostic factors were analyzed and correlated with disease-free survival (DFS) and overall survival (OS). Results: Five-year DFS and OS for the whole group were 29% and 49% respectively. On the univariate analysis, patients without axillary nodal involvement at the time of mastectomy had significantly greater 5-year DFS and OS than patients with nodal involvement (51% vs. 14% and 70% vs. 34% respectively, p〈 0.05). DFS was also significantly better for patients receiving systemic therapy after local treatment (31% vs. 19%). On the multivariate analysis, absence of nodal involvement and systemic therapy were associated with longer DFS (p = 0.044 and p = 0.008, respectively) and OS (p = 0.009 and p = 0.011, respectively). None of the other factors analyzed including menopausal status, T-stage, number of involved nodes, receptor status, adjuvant therapy, sites of first recurrence, or time from mastectomy to first recurrence had a predictive value for DFS and OS. Conclusion: Patients with stage IV-NED have poor prognosis due to early development of metastatic disease. Absence of axillary nodal involvement at the time of mastectomy and systemic therapy following local management is associated with improved DFS and OS. These results suggest that systemic therapy after local treatment in stage IV-NED is indicated. Poor prognosis in patients with previous nodal involvement warrants new approaches.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006090319083
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  • 64
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    Electronic Resource
    Combined effect of vitamin D3 analogs and paclitaxel on the growth of MCF-7 breast cancer cells in vivo (1999)
    Springer
    Breast cancer research and treatment 53 (1999), S. 113-120 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; BNX nude mouse ; paclitaxel ; Vitamin D3 analogs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Vitamin D3 analogs and paclitaxel (Taxol) are able to inhibit the in vitro growth of a variety of malignant cells including breast cancer cells. These two compounds decrease growth by different mechanisms and they have non-overlapping toxicities. We examined the abilities of three vitamin D3 compounds to inhibit growth of a human mammary cancer (MCF-7) in BNX triple immunodeficient mice either alone or with Taxol. Vitamin D3 analogs were 1,25(OH)2D3 (code name, Compound C), 1,25(OH)2-16-ene-23-yne-19-n or-26,27-F6-D3 (Compound LH), and 24a,26a,27a,-trihomo-22,24-diene-1,25(OH)2D3 (EB1089). At the doses chosen, the antitumor effect of vitamin D3 analogs alone was greater than that of Taxol alone, and an additive effect was observed when a vitamin D3 analog and Taxol were administered together. EB1089 was the most potent compound, and the EB1089 plus Taxol was the most active combination, decreasing the tumor mass nearly 4-fold compared to controls. Weight-gain in each of the experimental cohorts at the end of the study was less than the control group, but the gain was significantly less in only two experimental groups (those receiving either EB1089 or Compound C plus Taxol). None of the animals became hypercalcemic, and their complete blood counts, serum electrolyte analyses, and liver and renal functions were all fairly similar and within the normal range. In summary, this combination of a vitamin D3 analog and Taxol has the potential to be a therapy for breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006123819675
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  • 65
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    Comparative analysis of breast cancer recurrence risk for patients receiving or not receiving adjuvant cyclophosphamide, methotrexate, fluorouracil (CMF). Data supporting the occurrence of ‘cures’ (1999)
    Springer
    Breast cancer research and treatment 53 (1999), S. 209-215 
    Details
    ISSN: 1573-7217
    Keywords: adjuvant chemotherapy ; breast cancer ; cure ; early recurrences ; late recurrences ; recurrence risk pattern
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To comparatively analyse the risk of recurrence at given times after surgery for breast cancer patients receiving or not receiving adjuvant CMF. Patients and methods: A total of 1452 node positive patients, who entered controlled clinical trials carried out at the Milan Cancer Institute and underwent radical or modified radical mastectomy for operable breast cancer, were examined. In 575 cases no further treatment was performed, whereas 877 pts were given 6 or 12 courses of adjuvant Cyclophosphamide, Methotrexate, Fluorouracil (CMF). The recurrence risk was estimated by the event-specific hazard rate for first failure and distant metastases, and, following Efron, hazard rates were fitted by logistic regression models. Results: The hazard rate for first failure and distant metastases showed a double peaked pattern for both treated patients and controls, with a first major peak at about 18–24 months from surgery (early metastases), a second minor peak at the 5th–6th year, and a tapered plateau-like tail extending over 10 years from surgery (late metastases). As expected, the recurrence risk of CMF treated patients was lower than the corresponding risk of patients undergoing surgery only. However, the difference was highly evident for early recurrences, while it declined and disappeared afterwards. Conclusion: Our findings confirm previous reports on patients not receiving adjuvant chemotherapy, suggesting that the recurrence risk for operable breast cancer has a multipeak pattern. As far as CMF treated patients are concerned, the unchanged peak timing together with the early recurrence risk reduction in comparison to controls are much more consistent with the real nonappearance of some early recurrences (putatively ‘cured’ patients) than with the delay in their manifestation. As late relapsing patients seem to have at most marginal benefits from adjuvant CMF, ways to recognize patients doomed to have late recurrence and new ways for treating micrometastases resulting in late recurrences are required.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006134702484
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  • 66
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    Analyzing prognostic factors in breast cancer using a multistate model (1999)
    Springer
    Breast cancer research and treatment 54 (1999), S. 83-89 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; multivariate analysis ; multistate model ; prognostic factors ; risk ; survival analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In breast cancer clinical research, an important goal is to analyze how factors are seen to affect the disease process. Meanwhile, the disease progression is not fully modelled using standard analysis since transitions between intermediate events such as local-regional recurrences (LRR) or metachronous contralateral breast cancer (MCBC) are not considered. In the present study, the progression of disease was modelled using a multistate model. By this approach, we assessed transitions during the course of the disease and studied prognostic factors for each transition. The model was applied to 6,185 patients with unilateral ductal invasive breast cancer, clinical stage I through III, treated between 1981 and 1988 at the Curie Institute. At first diagnosis, high clinical stage, high histological grade, positive lymph nodes, and age less than 40 years were associated with increased risks of LRR, metastases, or death. Except age, the same factors remained predictive for metastases or death following LRR. Chemotherapy for the first cancer was associated with a decreased risk for developing MCBC. As the time interval from diagnosis of the primary tumor to that of a local or contralateral recurrence increased, the risk of metastases or death decreased. Nodal status for the first tumor and clinical stage for the contralateral tumor increased the risk of metastases or death following MCBC. Conversely, the risk decreased for patients who received adjuvant hormone therapy following MCBC. In conclusion, the multistate model offers us a much more appropriate way to study prognostic factors for each transition in breast cancer disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006197524405
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  • 67
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    Electronic Resource
    Methodological arguments for the necessity of randomized trials in high-dose chemotherapy for breast cancer (1999)
    Springer
    Breast cancer research and treatment 54 (1999), S. 31-38 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; high-dose chemotherapy ; randomized trials ; stem-cell transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the past ten years high-dose chemotherapy with autologous haematopoetic stem-cell support (HD-CT) has increasingly been used for breast cancer. But the vast majority of trials are small phase I/II studies showing until now not enough evidence that HD-CT is superior to conventional-dose chemotherapy (CD-CT). In contrast to this, the public perception of this treatment is different. Patients as well as physicians often uncritically believe in reports contrasting the positive results obtained in case series treated by HD-CT with those of historical control groups. This leads to the problem that many patients and also clinicians are not willing to participate in randomized trials on this topic. A critical assessment of current knowledge on the effectiveness of HD-CT in breast cancer is given. The problems related to the use of historical controls, in general, and especially in the setting of HD-CT are demonstrated. Using data of patients treated with CD-CT within trials of the German Breast Cancer Study Group (GBSG) it will be shown that results similarly favorable to those reported from patients treated with a high-dose regimen may be produced using quite simple selection mechanisms. Comparisons of patients treated with HD-CT with historical control groups of patients treated with CD-CT may be misleading. A valid treatment comparison is only possible by means of large randomized trials. Clinicians should participate in the ongoing trials and enter all eligible patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006111821492
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  • 68
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    Electronic Resource
    Diet and risk for breast cancer recurrence and survival (1999)
    Springer
    Breast cancer research and treatment 53 (1999), S. 241-253 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; diet ; recurrence ; survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Dietary factors may influence the risk for breast cancer and also the prognosis following diagnosis and treatment. The aim of this study was to assess whether self-reported prediagnosis diet or other patient factors associated with breast cancer incidence were predictive of recurrence and survival. Patients (n=149) diagnosed with primary breast cancer between 1989 and 1991 were followed for five or more years. Total energy (hazard ratio (HR)=1.58, 95%, confidence interval (CI)= 1.05, 2.38) as well as total (HR = 1.46, 95% CI = 1.05, 2.01), saturated (HR = 1.79,95% CI = 1.05, 3.04), and monounsaturated (HR = 1.65, 95% CI = 1.09,2.49) fat intakes were associated with increased risk, and energy-adjusted bread and cereal consumption (HR = 0.55, 95% CI = 0.33, 0.93) with decreased risk of recurrence. Both total energy (HR = 1.58, 95% CI = 1.03, 2.43) and polyunsaturated fat (HR = 1.84, 95% CI = 1.09, 3.13) intakes were associated with an increased risk of death. All associations between dietary fat and recurrence and survival attenuated following energy adjustment. Oral contraceptive use (HR = 1.28, 95% CI = 1.03, 1.60), lymph node positive status (HR = 2.36, 95% CI = 1.01, 5.49), and tumor stage (HR = 2.22, 95% CI = 1.02, 4.81) were associated with increased risk of recurrence. Tumor stage (HR = 4.96, 95% CI = 1.86, 13.23), lymph node positive status (HR = 3.31, 95% CI = 1.38, 7.95, and estrogen receptor negative status (HR = 2.46, 95% CI = 1.02, 5.94) were associated with increased risk, and arm muscle circumference (HR = 0.27, 95% CI = 0.09, 0.86) and mammographic utilization (HR = 0.77, 95% CI = 0.61, 0.98) with decreased risk of death. Higher levels of energy, fat intakes, and selected patient characteristics (particularly disease stage and anthropometric indicators of adiposity) appear to increase risk of recurrence and/or shortened survival following the diagnosis of breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006190820231
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  • 69
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    Electronic Resource
    Recognition of an epitope of a breast cancer antigen by human antibody (1999)
    Springer
    Breast cancer research and treatment 53 (1999), S. 279-290 
    Details
    ISSN: 1573-7217
    Keywords: human antibody ; antigen epitope ; breast cancer ; peptide ; retinoblastoma binding protein 1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A novel tumor-associated peptide epitope KASIFLK expressed preferentially by breast cancer cells was identified using an IgG antibody from a breast cancer patient. A cDNA library from a MCF-7 breast cancer cell line was screened to isolate three cDNA clones that were immunoreactive with this antibody. KASIFLK was located in clones 27 and 40, both of which were identical to the cDNA and protein sequence of retinoblastoma binding protein 1 (RBP1, 250–256). An affinity-purified IgG antibody against the peptide epitope was completely absorbed by cytoplasmic extracts of MCF-7 cells. Immunohistochemical staining using this antibody revealed the antigen in MCF-7 cells and in 12 of 15 primary breast cancer tissues and 3 of 34 other cancer tissues, but in none of 6 normal breast tissues. Anti-KASIFLK antibody titers were significantly higher in sera of 55 breast cancer patients than in sera from 30 normal healthy donors (P 〉 0.001). These results suggest that KASIFLK or its cross-reactive epitope is a breast cancer antigen and is immunogenic in humans.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006115922401
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  • 70
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    Synergistic cooperation between c-Myc and Bcl-2 in lymph node progression of T1 human breast carcinomas (1999)
    Springer
    Breast cancer research and treatment 54 (1999), S. 39-45 
    Details
    ISSN: 1573-7217
    Keywords: apoptosis ; Bcl-2 ; breast cancer ; c-Myc ; metastasis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The overexpression of Bcl-2, an anti-apoptotic oncogene, identifies human T1 breast cancer patients who have an increased risk of lymph-node metastasis. We examined in these patients (n=142) whether the c-Myc oncogene influences metastatic progression in conjunction or not with Bcl-2 expression and the loss of apoptosis in tumors. The association between Bcl-2 and lymph-node metastasis was only significant when c-Myc was concomitantly expressed (χ2 test, p=0.008). Moreover, very large associations (pOR=6.4) between c-Myc and lymph-node metastasis were observed among Bcl-2 positive tumors and tumors with loss of apoptosis (pOR=8.4). In contrast, the metastatic advantage linked to Bcl-2 was decreased (pOR=2) when c-Myc was not coexpressed. It is concluded that the synergism between Bcl-2 and c-Myc oncogenes may promote metastasis in breast tumors, linked to loss of apoptosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006120006471
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  • 71
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    Tumor flow in malignant breast tumors measured by Doppler ultrasound: an independent predictor of survival (1999)
    Springer
    Breast cancer research and treatment 54 (1999), S. 65-71 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; blood flow ; Doppler ; prognosis ; ultrasound
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of this study was to investigate tumor blood flow in breast cancers with regard to its impact on the overall survival of patients. Tumor blood flow was assessed in seventy-four patients with primary breast cancer by the use of color-coded Doppler ultrasound techniques. Preoperatively obtained Doppler frequency spectra were analyzed for peak systolic flow velocity (Vmax). Color Doppler signals were detected in 71 (96%) of the breast tumors. Out of 74 patients, 17 experienced a relapse or distant metastasis, and 15 women had died due to breast cancer at the time of data analysis. The mean Vmax of the patients who had died was 0.27 m s−1, whereas survivors showed a mean Vmax of 0.16 m s−1(p=0.01. Vmax, nodal status, and progesterone receptor status remained the only significant factors of overall survival in the multivariate model, whereas tumor size, tumor grade, and estrogen receptor status failed to retain prognostic significance. Moreover, Vmax was identified as the most important prognostic marker for survival in our series. The five-year-survival was 82.3% in Vmax≤ 0.25 m s−1 patients versus 36.6% in women with tumor flow greater than 0.25 m s−1. Patients with Vmax 〉 0.25 m s−1 experienced a 4.33-fold increased risk of death secondary to the underlying disease. In summary, our data showed that tumor blood flow velocity measured by ultrasonography is an independent prognostic factor of survival in breast cancer patients. Furthermore, tumor flow velocity allows identification of patients at very high risk of death due to breast cancer. Large scale clinical trials should evaluate the clinical usefulness and future impact of this procedure for adjuvant treatment decisions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006148812831
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  • 72
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    Rural breast cancer treatment: evidence from the Reaching Communities for Cancer Care (REACH) project (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 59-66 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; neoplasm ; recommendations ; rural ; treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. Research shows that rural populations are more likely than their urban counterparts to be diagnosed with late‐stage cancer, but less is known about appropriateness of cancer treatment in rural locations after diagnosis. The objective of this analysis was to assess the degree to which rural breast cancer treatment was received in concordance with national recommendations. Methods. Data came from 251 stage I and II breast cancer patients residing in rural North Carolina. State‐of‐the‐art care was defined using the National Cancer Institute's (NCI) physician data query (PDQ) database, and cases were categorized into appropriate primary and/or adjuvant treatment. Chi‐square and Fishers' exact tests were used to assess changes in appropriate treatment over time (1991–1996) and between stage. Multiple logistic regression was used to determine whether any patient or disease characteristics were associated with receipt of appropriate treatment. Results. Most (81–90%) of the breast cancer cases received the appropriate primary therapy (mastectomy or lumpectomy followed by radiation therapy); of these, the majority received a mastectomy (66–72%). Fewer women received adjuvant therapy as recommended (27–61%), although significantly more stage II than stage I cases did so (p≤0.05). Regression showed that stage and estrogen‐receptor (ER) status were associated with appropriate therapy. Conclusions. The findings suggest that there exist deviations from NCI established treatment recommendations among rural breast cancer patients. More research is needed to develop better methods for dissemination of state‐of‐the‐art cancer information to rural physicians and patients, and to understand how treatment decisions are made.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006279117650
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  • 73
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    Randomized trial of diethylstilbestrol vs. tamoxifen in postmenopausal women with metastatic breast cancer. An updated analysis (1999)
    Springer
    Breast cancer research and treatment 54 (1999), S. 117-122 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; diethylstilbestrol ; postmenopausal women ; tamoxifen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract One hundred fifty‐one postmenopausal women with progressive metastatic breast cancer and no prior hormonal therapy were treated with either diethylstilbestrol (DES) or tamoxifen (TAM). One hundred forty‐three eligible patients were followed until death or for a minimum of 14.1 years on the DES arm or 16.7 years on the TAM arm. The overall objective response was 42% for DES and 33% for TAM (p=0.31) and the median duration of response was 11.8 months for DES and 9.9 months for TAM (p=0.38). Duration of response and progression‐free survival were not found to be significantly different between DES and TAM (p=0.32 and 0.65, respectively). The median survival was 3.0 years for DES vs. 2.4 years for TAM. The 5‐year survival was 35% for the DES arm and 16% for the TAM arm. Survival was significantly better for women on DES than for women on TAM (adjusted p=0.039). Review of records did not show any difference in pattern of treatment failure or subsequent treatments in the DES and TAM arms. Treatment with DES was more commonly associated with toxicity such as nausea, edema, vaginal bleeding, and cardiac problems, whereas hot flashes were commonly seen with TAM therapy. The initial treatment with DES is associated with increased survival. The basis of this survival advantage is not known. TAM still is the preferred agent in the treatment of metastatic breast cancer, but this trial underscores the fact that estrogens have activity and remain in the armamentarium for treatment of selected patients with metastatic breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006185805079
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  • 74
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    Invasion marker PAI‐1 remains a strong prognostic factor after long‐term follow‐up both for primary breast cancer and following first relapse (1999)
    Springer
    Breast cancer research and treatment 54 (1999), S. 147-157 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; cathepsin D ; PAI‐1 ; prognosis ; S‐phase fraction ; uPA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In 1991, our group was the first to report the prognostic strength of plasminogen activator inhibitor type 1 (PAI‐1) in primary breast cancer. The prognostic impact of invasion markers PAI‐1 and urokinase‐type plasminogen activator (uPA) on disease‐free survival (DFS) and overall survival (OS) in breast cancer has since been independently confirmed. We now report on the prognostic impact of PAI‐1 and uPA after long‐term median follow‐up of 77 months for our cohort (n=316). Levels of uPA, PAI‐1, and cathepsin D were determined in tumor tissue extracts by immunoenzymatic methods. S‐phase fraction (SPF) was measured flowcytometrically in paraffin sections. Using log‐rank statistics, optimized cutoffs were found for PAI‐1 (14 ng/mg), uPA (3 ng/mg), cathepsin D (41 pmol/mg), and SPF (6%). In all patients, various factors (PAI‐1, uPA, nodal status, SPF, cathepsin D, grading, tumor size, hormone receptor status) showed significant univariate impact on DFS. In Cox analysis, only nodal status (p 〈 0.001, RR: 3.1) and PAI‐1 (p 〈 0.001, RR: 2.7) remained significant. In node‐negative patients (n = 147), PAI‐1, uPA, and SPF had significant univariate impact on DFS, whereas in Cox analysis, only PAI‐1 was significant. PAI‐1 was also significant for DFS within subgroups defined by established factors. In CART analysis, uPA enhanced the prognostic value of PAI‐1 and nodal status for determination of a very‐low‐risk subgroup. For OS, only lymph node status and PAI‐1 were significant in multivariate analysis. PAI‐1 levels in the primary tumor were also a significant prognostic marker for survival after first relapse in both univariate and multivariate analysis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006118828278
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  • 75
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    Electronic Resource
    Association between endometrial cancer and tamoxifen treatment of breast cancer (1999)
    Springer
    Breast cancer research and treatment 54 (1999), S. 255-260 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; endometrial cancer ; tamoxifen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A retrospective cohort‐study in 4109 breast cancer patients was undertaken to determine how tamoxifen affected the risk of endometrial cancer. Data on 1701 tamoxifen‐treated women were analysed. Two thousand four hundred and eight non‐tamoxifen users served as control group. The occurrence of new primary uterine cancers was assessed by computerized linkage to the Austrian Cancer Registry. Twenty‐five women who subsequently developed endometrial cancer were identified. Eight uterine cancers occurred in the tamoxifen group, whereas 17 uterine cancers were found in the control group. The estimate of the relative risk (RR) showed an increased risk to develop endometrial cancer for the tamoxifen group RR 1.136 (95% CI 0.71; 1.80). Analysis of relevant confounding variables did not show any differences in the two groups. In conclusion, this retrospective study demonstrated a non‐significant increased risk of endometrial cancer in women receiving tamoxifen as treatment for breast cancer. However, the magnitude of RR and the absolute number of endometrial cancer cases in this long term observation demonstrate clearly that the clinical benefit of tamoxifen therapy greatly outweighs the risk.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006126411210
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  • 76
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    Tissue inhibitor of metalloprotease (TIMP)‐1 and proliferative behaviour of clonal breast cancer cells (1999)
    Springer
    Breast cancer research and treatment 54 (1999), S. 235-244 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; cell culture ; cell growth ; TIMP‐1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the present paper, we have examined whether human tissue inhibitor of metalloprotease‐1 (hTIMP‐1) is able to exert a growth factor‐like effect on two clonal cell lines (BC‐3A and BC‐61), isolated from a parental line of human breast carcinoma cells (8701‐BC), and endowed with different growth and invasive behaviour ‘in vitro’ and in nude mouse. The data obtained indicate that only the more tumorigenic clonal cell line (BC‐61) is responsive to hTIMP‐1 treatment by increasing its proliferative rate in a dose‐dependent manner. It was also found that BC‐61 cells selectively express a transmembrane protein of about 80 kDa able to bind hTIMP‐1 ‘in vitro’ and ‘in vivo’ with high affinity (Kd of 0.07 ± 0.004   nM), and that treatment of BC‐61 cells with a proliferation‐promoting concentration of hTIMP‐1 is able to stimulate tyrosine‐targeted phosphorylation. The cumulative results obtained strongly support the hypothesis that hTIMP‐1, ‘classically’ regarded as a collagenase inhibitor, may be a crucial element of the extracellular signalling network during breast cancer development by controlling cell growth phenotype in autocrine and paracrine manner, and that intratumoural heterogeneity for the biological response to TIMP‐1 may exist within the composite cell population of the primary tumour site.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006121129382
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  • 77
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    Allelic loss of the PTEN region (10q23) in breast carcinomas of poor pathophenotype (1999)
    Springer
    Breast cancer research and treatment 57 (1999), S. 237-243 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; LOH ; polymorphic marker ; poor prognosis ; PTEN
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Loss of heterozygosity (LOH) in loci of the 10q23 region that harbor the PTEN gene and mutations in the sequence of this gene have been found in several primary human tumors including breast carcinomas, suggesting that this gene could be implicated in their pathogenesis. We investigated allelic losses in microsatellites of the 10q23 region, and their correlations with nine pathologic parameters in 105 breast carcinomas. The LOH analysis was performcd by amplifying DNA by PCR, using five markers of the 10q23 region (D10S1687, D10S541, D10S2491, D10S583 and D10S571). LOH in at least one marker of the PTEN region was found in 29.5% of tumors. The statistical comparison between carcinomas with and without LOH in terms of the pathologic parameters showed significant differences in age (p=0.03), lymph node metastases (p=0.02), and higher histological grade (p=0.02); a trend toward significance was found for progesterone receptors (p=0.05). LOH in an individual marker and statistically significant relationships to tumor characteristics were observed at locus D10S541 for lymph node metastases (p=0.04), at D10S2491 (intragenic to the PTEN gene) for lymph node metastases (p=0.02), and at D10S583 for progesterone receptors (p=0.01) and for high grade (p=0.03). These results suggest the PTEN gene, or other genes of the 10q23 region, could be functionally related to breast cancer, probably influencing the development of histological features associated with poor prognosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006273516976
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  • 78
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    Electronic Resource
    Insulin‐like growth factor (IGF)‐I rescues breast cancer cells from chemotherapy‐induced cell death – proliferative and anti‐apoptotic effects (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 1-10 
    Details
    ISSN: 1573-7217
    Keywords: apoptosis ; breast cancer ; doxorubicin ; IGF‐I ; paclitaxel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Insulin‐like growth factor (IGF)‐I protects many cell types from apoptosis. As a result, it is possible that IGF‐I‐responsive cancer cells may be resistant to apoptosis‐inducing chemotherapies. Therefore, we examined the effects of IGF‐I on paclitaxel and doxorubicin‐induced apoptosis in the IGF‐I‐responsive breast cancer cell line MCF‐7. Both drugs caused DNA laddering in a dose‐dependent fashion, and IGF‐I reduced the formation of ladders. We next examined the effects of IGF‐I and estradiol on cell survival following drug treatment in monolayer culture. IGF‐I, but not estradiol, increased survival of MCF‐7 cells in the presence of either drug. Cell cycle progression and counting of trypan‐blue stained cells showed that IGF‐I was inducing proliferation in paclitaxel‐treated but not doxorubicin‐treated cells. However, IGF‐I decreased the fraction of apoptotic cells in doxorubicin‐ but not paclitaxel‐treated cells. Recent work has shown that mitogen‐activated protein kinase (MAPK) and phosphotidylinositol‐3 (PI‐3) kinase are activated by IGF‐I in these cells. PI‐3 kinase activation has been linked to anti‐apoptotic functions while MAPK activation is associated with proliferation. We found that IGF‐I rescue of doxorubicin‐induced apoptosis required PI‐3 kinase but not MAPK function, suggesting that IGF‐I inhibited apoptosis. In contrast, IGF‐I rescue of paclitaxel‐induced apoptosis required both PI‐3 kinase and MAPK, suggesting that IGF‐I‐mediated protection was due to enhancement of proliferation. Therefore, IGF‐I attenuated the response of breast cancer cells to doxorubicin and paclitaxel by at least two mechanisms: induction of proliferation and inhibition of apoptosis. Thus, inhibition of IGF‐I action could be a useful adjuvant to cytotoxic chemotherapy in breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006208721167
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  • 79
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    Electronic Resource
    Policy guidelines for the utilization of formalin-fixed, paraffin-embedded tissue sections: the UNC SPORE experience (1999)
    Springer
    Breast cancer research and treatment 58 (1999), S. 31-39 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; formalin-fixed paraffin blocks ; policy ; quality control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Paraffin blocks represent a valuable resource that has allowed investigators to apply today's technology to address scientific questions in a shorter period of time and in more diverse populations than would have been possible with fresh or frozen tissue. However, in addition to being an exhaustible resource, there is concern regarding the appropriate use of these tissues, both with respect to medical or legal considerations and quality control and quality assurance practices. We describe policy guidelines to address these concerns, including: safeguards to address medical/legal and patient confidentiality issues, quality control and quality assurance for tissue sectioning, processing and storage, database management for sample tracking, and scientific review for utilization of specimens. These policies and procedures have been developed and implemented by the University of North Carolina (UNC) Specialized Program of Research Excellence (SPORE) in the Breast Cancer Immunohistochemistry (IHC) Core laboratory, in collaboration with our study pathologists, participants, and research investigators. It is our hope that the information and experience described here may stimulate discussion that can ultimately lead to a uniform policy for handling formalin-fixed paraffin-embedded tissues in research.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006354627669
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  • 80
    Electronic Resource
    Electronic Resource
    Short and long‐term effects on survival in breast cancer patients treated by primary chemotherapy: an updated analysis of a randomized trial (1999)
    Springer
    Breast cancer research and treatment 58 (1999), S. 151-156 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; long term effect ; primary chemotherapy ; short term effect ; weighted logrank tests
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A potential advantage of primary over adjuvant chemotherapy in breast cancer survival had been proposed on theoretical grounds. In 1994, early results of the S6‐trial comparing primary chemotherapy vs. adjuvant chemotherapy for operable breast cancer in 390 premenopausal patients had shown significant improvement in survival of the primary chemotherapy arm (p=0.04). An updated analysis conducted in 1995 showed the disappearance of this difference between the two arms (p=0.18). In the present analysis, we investigated the potential short and long‐term benefits attributable to primary chemotherapy by applying weighted logrank tests designed to assess specifically these effects. Results were compared to those obtained with the classical logrank test. At a median follow‐up of 105 months, a significant short‐term survival benefit (p=0.02) in favor of the primary chemotherapy has been shown. However, no long‐term survival benefit (p=0.36) could be documented. The classical logrank test had revealed no significant difference (p=0.24) between the two groups but the proportional hazard assumption being rejected (p=0.04), the efficiency of this test can be questioned. Results using the present analysis suggested that primary chemotherapy delayed early death rates, without significantly modifying long‐term event rates. It emphasizes that a short‐term effect which is not necessarily associated with a long‐term benefit may be seen at an early evaluation and disappear later on.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006339918798
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  • 81
    Electronic Resource
    Electronic Resource
    Staging efficacy of breast cancer with sentinel lymphadenectomy (1999)
    Springer
    Breast cancer research and treatment 57 (1999), S. 221-229 
    Details
    ISSN: 1573-7217
    Keywords: axillary dissection ; breast cancer ; prognosis ; sentinel node dissection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Seventy‐two patients underwent dye‐guided or dye‐ and gamma probe‐guided sentinel lymphadenectomy (SLND) followed by complete axillary lymph node dissection (ALND). The results of imprint cytology, frozen sections, and permanent sections of the sentinel lymph node (SLN) were compared to each other and to the histologic findings in the nonsentinel nodes. The SLN was identified in 62 (88%) of 72 patients. Evaluation of the SLN on the permanent sections yielded a diagnostic accuracy of 95%, a sensitivity of 89%, and a specificity of 100, although the reliability of SLN diagnosis using frozen sections or imprint cytology is limited. Therefore, it may be concluded that SLND with multiple sectioning and histopathologic examination of the SLNs can predict the presence or absence of axillary‐node metastases in patients with breast cancer. However, further studies will be needed to investigate the value of SLND in respect to the long‐term regional control and any possible detriment or benefit to survival, before it can replace routine ALND as the preferred staging operation for operable breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006268426526
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  • 82
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    Electronic Resource
    SUM-159PT cells: a novel estrogen independent human breast cancer model system (1999)
    Springer
    Breast cancer research and treatment 58 (1999), S. 193-204 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; estrogen independent ; MCF-7 cells ; metastases ; SUM-159PT cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Breast cancer remains one of the most common malignant diseases in women in North America and Western Europe, yet therapies for the more aggressive estrogen independent tumors are limited and few model systems are available for the study of this type of breast cancer. In these studies, we characterized a novel estrogen independent breast cancer cell line, SUM-159PT. SUM-159PT cells are epithelial in origin, demonstrated by expression of cytokeratin 18. SUM-159PT cells are estrogen independent, demonstrated by lack of estrogen receptor (ER) protein and ER ligand binding studies. Furthermore, SUM-159PT cells injected subcutaneously or orthotopically are tumorigenic in ovariectomized athymic nude mice in the absence of estradiol supplementation. SUM-159PT cells are capable of invading through an 8 μm Matrigel membrane and display a stellate morphology in Matrigel, indicative of a metastatic phenotype. Correlating with this phenotype, we have detected secondary tumors upon inoculation of SUM-159PT cells into the mammary fat pad. To further investigate the metastatic potential of the SUM-159PT cells, we examined the expression of two proteins, vimentin and E-cadherin, implicated in the transition of carcinoma cells to a metastatic phenotype. Western blot and immunohistochemical analysis demonstrated that both SUM-159PT cells and xenografts express vimentin. No expression of E-cadherin was detected in SUM-159PT cells. Our data indicate that despite estrogen independence, SUM-159PT cells are growth inhibited in vitro by compounds such as 1,25(OH)2D3, transforming growth factor β (TGF-β), and the phorbol ester TPA. These studies indicate that SUM-159PT cells represent a good model system for the study of late stage estrogen independent, invasive breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006331716981
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  • 83
    Electronic Resource
    Electronic Resource
    Expression of the estrogen receptor-associated immunophilins, cyclophilin 40 and FKBP52, in breast cancer (1999)
    Springer
    Breast cancer research and treatment 58 (1999), S. 265-278 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; estrogen receptor ; expression ; immunophilins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The estrogen receptor α (ERα) is implicated in the development of breast cancer. The immunophilins, cyclophilin 40 (CyP40) and FKBP52, are associated with ERα and other steroid receptors in mutually exclusive heterocomplexes and may differentially modulate receptor activity. Since previous studies have not assessed the levels of these immunophilins in breast cancer, we examined 10 breast cancer cell lines for mRNA and protein expression of CyP40 and FKBP52 and for amplification of the CyP40 gene. In addition, 26 breast carcinomas, including seven with matched normal breast tissue, were examined for mRNA expression of both immunophilins. CyP40 and FKBP52 were ubiquitously expressed in breast cancer cell lines, but there were significant differences in their pattern of expression. FKBP52 protein levels were generally an order of magnitude greater than those for CyP40. FKBP52 mRNA expression correlated strongly with protein expression and was significantly higher in ERα-positive compared with ERα-negative cell lines. However, CyP40 mRNA expression did not correlate with protein expression, nor did expression of this immunophilin correlate with ERα status. Relatively high expression of CyP40 in one cell line (BT-20) could be attributed to amplification of the CyP40 gene. Both immunophilins were also ubiquitously expressed in breast carcinomas, and we demonstrate for the first time that both CyP40 and FKBP52 mRNA are overexpressed in breast tumors compared to matched normal breast controls. The overexpression of CyP40 and FKBP52, coupled with relative differences in their expression in tumors, may have important functional implications for ERα and other steroid receptors in breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006390804515
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  • 84
    Electronic Resource
    Electronic Resource
    The relation of breast size to breast cancer risk in postmenopausal women (United States) (1999)
    Springer
    Cancer causes & control 10 (1999), S. 115-118 
    Details
    ISSN: 1573-7225
    Keywords: anthropometry ; breast cancer ; breast size ; case-control study ; risk factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: Breast size has been hypothesized to predict a woman's risk of breast cancer although studies in the main have not supported an association. In a large, population-based case-control study we examined whether breast size might emerge as a significant risk factor among very lean women in whom breast size might be a truer reflection of the volume of gland mass at risk for malignant change. Methods: The data derive from a population-based case- control study of women aged 50 to 79 years conducted in several New England states and Wisconsin. Incident cases of invasive breast cancer (n=2015) were identified through state tumor registries and controls (n=2556) were selected at random within age strata from population lists. Telephone interviews were conducted to obtain information on known and suspected risk factors which included bra dimensions (cup and back size) prior to a first birth, or at the age of 20 for nulliparous women. Results: We observed a significant positive association for cup size which was limited to women who were the most lean as young adults based on chest circumference. Among those reporting a chest size under 34 inches multivariate-adjusted relative risks were 1.34 (95% CI: 1.04 to 1.74) for cup size B, and 1.76 (95% CI: 1.04 to 3.01) for cup size C and larger, compared to a cup size smaller than B, and the trend for increasing cup size was statistically significant (P=0.005). There was no relation with breast size among women reporting an average or larger back circumference (34 inches or larger). Conclusion: Breast size before a pregnancy is a positive predictor of postmenopausal breast cancer, but this association is limited to those who were especially lean as young women.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008801131831
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  • 85
    Electronic Resource
    Electronic Resource
    Evaluation of breast cancer incidence: is the increase due entirely to mammographic screening? (1999)
    Springer
    Cancer causes & control 10 (1999), S. 333-337 
    Details
    ISSN: 1573-7225
    Keywords: breast cancer ; cancer control ; incidence ; mammographic screening
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objectives: To examine the trends in the incidence rates of breast cancer in a population with mammographic screening and in the unscreened women within that population. Methods: Data consisted of incident cases of breast cancer notified to the Victorian Cancer Registry in Victoria, Australia, between 1988 and 1996 and cases detected in the population-based BreastScreen Program. These data were grouped by age (25–39, 40–49, 50–59, 60–69 and ≥70 years of age) and size of tumor (≤10 mm, 〉 10–≤15 mm, and 〉 15mm). Poisson regression modeling was used to examine trends by age, tumor size, calendar year and availability of screening. Results: The incidence rate of breast cancer in the total population increased between 1988 and 1996. The greatest increase was seen after 1993 when population-based screening became available. In unscreened women, modeling demonstrated a statistically significant (p 〈 0.01) 1.5% annual increase in the incidence rate. The annual increase in this rate differed by size of tumor and was approximately 8% (p 〈 0.01) for small tumors (≤ 10 mm) but not significant for tumors 〉 10 mm. The greatest increase was in small tumors for women ≥ 50 years of age. Conclusion: The incidence of breast cancer has increased since population-based mammographic screening was introduced in 1994. The rate in unscreened women also showed a significant increase. This was greatest in small tumors for women ≥ 50 years of age. Whether this will translate into an increase in mortality is uncertain and long-term monitoring is required to determine if cohort and period effects impact on the underlying incidence of breast cancer in Victoria.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008949819969
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  • 86
    Electronic Resource
    Electronic Resource
    In-utero and early life exposures in relation to risk of breast cancer (1999)
    Springer
    Cancer causes & control 10 (1999), S. 561-573 
    Details
    ISSN: 1573-7225
    Keywords: adolescent ; breast cancer ; breast fed ; epidemiology ; maternal age ; preeclampsia ; prenatal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objectives: In response to a hypothesis by Trichopoulos that risk of adult breast cancer is related to high estrogen exposure in utero, studies have been undertaken using proxy indicators of prenatal estrogens. The epidemiologic studies addressing these early factors will be reviewed, consistency with proposed biologic mechanisms will be addressed and recommendations for future research will be presented. Methods: All studies identified in the literature addressing these in utero and early life factors related to adult breast cancer will be included in the review. The study results will be summarized by risk factor, followed by commentary on the findings. Results: Review of epidemiologic studies suggests strong risks related to having been born of a twin pregnancy and reduced risks from a preeclamptic or eclamptic pregnancy. Birthweights greater than 4000 grams have been associated with relative risks of 1.5–1.7 for breast cancer compared with normal birthweights (2500–2999 grams). Having been breastfed as an infant has been associated with a 20–35% reduction in risk of premenopausal breast cancer in four of six studies evaluating this factor. Some studies suggest an influence of older maternal age, perhaps only for firstborn offspring, but the data are not consistent. Smoking during the pregnancy does not seem to impart any risk for the daughter, severe nausea for two or three trimesters may be related to increased risk, and results are inconsistent for birth length, placental weight and gestational age. Conclusion: Although the results from epidemiologic studies assessing prenatal exposures are consistent with the hypothesis concerning estrogen exposure, the specific biologic mechanisms remain largely unknown. Relatively few epidemiologic studies have been published addressing these novel hypotheses; more studies with innovative research methods and analytic approaches are warranted to evaluate these exposures in the distant past.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008955110868
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  • 87
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    Electronic Resource
    Reduced telomere DNA content is correlated with genomic instability and metastasis in invasive human breast carcinoma (1999)
    Springer
    Breast cancer research and treatment 54 (1999), S. 59-64 
    Details
    ISSN: 1573-7217
    Keywords: aneuploidy ; breast cancer ; genomic instability ; metastasis ; prognostic markers ; telomeres
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Telomere shortening leads to genomic instability and has been correlated with poor outcome in several types of cancer. A recently described, robust titration assay was used to quantify telomere DNA content in frozen and paraffin-embedded specimens of 49 invasive human breast carcinomas, including tumors with normal or abnormal contents of genomic DNA, which produced regional, distant, or local disease. Telomere DNA contents ranged from 53% to 370% of the content in a reference DNA purified from normal placenta. Tumors were divided into three groups of approximately equal size based on increasing telomere DNA content. All of 16 tumors in the group with the least telomere DNA (Group I), were aneuploid compared to 9/17 tumors in the group with the most telomere DNA (Group III). The Chi-square test for trend indicated that tumors with the least telomere DNA were significantly more likely to be aneuploid than tumors with the most telomere DNA (p〈0.002). Twelve of 14 tumors in Group I also produced metastatic disease compared to 8/15 tumors in Group III. The Fischer Exact Test indicated that tumors with the least telomere DNA were significantly more likely to be metastatic than tumors with the most telomere DNA (p〈0.05). There was no association between telomere DNA content and patients’ age, tumors’ size, grade, stage, or fraction of cells in S-phase. The correlation of reduced telomere DNA content with aneuploidy and metastasis, both of which are associated with poor outcome in invasive breast carcinoma, implies that telomere DNA content also could have prognostic value.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006128228761
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  • 88
    Electronic Resource
    Electronic Resource
    The declining use of axillary dissection in patients with early stage breast cancer (1999)
    Springer
    Breast cancer research and treatment 53 (1999), S. 137-144 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; axillary node dissection ; cancer-directed surgery ; radiotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objectives: To determine any changes in usage of axillary dissection over time from 1983 to 1993, and to characterize those patients who do not receive axillary node dissection. Methods: A total of 129,946 female patients receiving cancer-directed surgery for early stage breast cancer, who were identified from the SEER (Surveillance, Epidemiology and End Results) program and diagnosed from 1983 to 1993, were included in the study. The surgical treatment and axillary dissection were based on treatment data collected by the SEER during the first course of therapy. Logistic regression analyses were used to assess the effect of patient and tumor characteristics on the likelihood of not receiving different types of treatment. Results: The percentage of women not receiving axillary dissection has increased over time, from 14.4% in 1983 to 16.8% in 1993. Nearly a quarter of women undergoing breast conserving surgery for local stage breast cancer receive neither axillary dissection nor radiotherapy. Older, unmarried, and non-white women and those with very small (〈0.5 cm) or very large (〉=4 cm) tumors were most likely to receive neither axillary node dissection nor irradiation. Among those not receiving axillary dissection, 42% had tumors 1–3 cm in size and were not receiving radiation therapy. Conclusions: There is an apparent divergence between the type of patient who has been recommended as an appropriate candidate for avoiding axillary dissection (those with small tumors and those who will receive adjuvant therapy) and those who are actually not receiving axillary dissection in the community.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006170811237
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  • 89
    Electronic Resource
    Electronic Resource
    Expression of epidermal growth factor receptor mRNA and protein in primary breast carcinomas (1999)
    Springer
    Breast cancer research and treatment 53 (1999), S. 167-176 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; EGFR mRNA ; epidermal growth factor receptor ; immunohistochemistry ; in situ hybridization ; oestrogen receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The expression of epidermal growth factor receptor (EGFR) mRNA and protein has been determined in a group of breast carcinomas and compared to oestrogen and progesterone receptor (ER, PgR) status, as well as pathological features. In situ hybridization using a digoxigenin-labelled oligonucleotide probe was applied to formalin-fixed paraffin-embedded sections, and immunohistochemistry was used to determine EGFR protein. EGFR mRNA was detected in 66% of carcinomas with a third having labelling similar to normal breast tissue, 22% heterogeneous weak to strong labelling, and 11% strong labelling. EGFR protein was detected in 36% and these tumours had a strong correlation to lack of ER and high histological grade. The presence of EGFR protein was strongly correlated with more intense labelling for EGFR mRNA (p 〈 0.0001). This contrasted with normal breast in which both EGFR protein and mRNA were present with varying degrees in both tumours and a normal breast control. The ER-/PgR- carcinomas showed the full range of EGFR mRNA labelling. It is postulated that oestrogen or oestrogen regulated proteins are involved in regulation of EGFR mRNA and protein. In a proportion of tumours lacking steroid receptors regulation is lost, leading to EGFR overexpression.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006194700667
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  • 90
    Electronic Resource
    Electronic Resource
    Applying the Nottingham Prognostic Index to a Swedish breast cancer population (1999)
    Springer
    Breast cancer research and treatment 53 (1999), S. 1-8 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; histopathological grade ; Nottingham Prognostic Index ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of this study was to assess the applicability of histopathological grading according to the protocol of Elston/Ellis and the Nottingham Prognostic Index (NPI) to a defined breast cancer population. The NPI is the sum of the individual scores concerning grade, tumour size, and lymph node status, each weighted according to regression coefficients of a Cox proportional hazard analysis and calculated for each individual breast cancer patient. 630 consecutive patients with invasive breast cancer diagnosed 1988–91 were retrospectively followed up and their tumours reviewed and graded. A Cox proportional hazard analysis was performed. Grade, lymph node status, and tumour size were statistically significant predictors of survival within the follow up period (median 7.2 years). Similar to NPI, a temporary index (Kalmar Prognostic Index, KPI) was derived and normalised to NPI for comparison (KPI(norm)). NPI and KPI(norm) gave similar prognostic power in spite of the differences of the patient populations from which the 2 indices were derived. Patients with NPI 4 or less had 0.66% breast cancer specific mortality during the follow up time. 14% of the patients with NPI 4.1–5 and 32% of those with an index sum 5.1–6 died from breast cancer during this time. Younger patients tended to have higher grade tumours. We advocate the common use of grade and the NPI in order to increase the comparability of groups of patients receiving different therapies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006052115874
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  • 91
    Electronic Resource
    Electronic Resource
    Analyses of microsatellite instability and the transforming growth factor‐β receptor type II gene mutation in sporadic breast cancer and their correlation with clinicopathological features (1999)
    Springer
    Breast cancer research and treatment 53 (1999), S. 33-39 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; microsatellite instability ; TGF‐β RII gene ; clinicopathological features ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To determine the incidence of microsatellite instability (MSI) and its relationship with both clinicopathologic parameters and patient survival, 101 cases of breast cancer were investigated. In addition, transforming growth factor‐β (TGF‐β) receptor type II (RII) gene mutation was also examined to clarify the relation to MSI in breast cancer development. MSI and RII gene mutation were screened by single strand conformation polymorphism (SSCP). The mutations of the RII gene were confirmed by a direct sequence. An association between the MSI status and the clinicopathological features was examined to assess the potential of the MSI status as a prognostic indicator in sporadic breast cancer cases. MSI was detected in 12 of 101 (11.9%) breast cancer cases. The positive MSI breast cancer cases showed relatively more advanced disease than negative MSI cases, and also exhibited relatively poorer prognoses. No RII gene mutations were observed in any of the breast cancer cases. Our data suggest that the MSI status may thus be a useful indicator for the prognosis of sporadic breast cancer cases. However, the breast seems to be an infrequent target organ for cancer development through RII gene mutations. As a result, tumor progression through this pathway appears to be related to organ specificity. For positive MSI breast cancers, other target genes therefore still need to be identified.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006167210269
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  • 92
    Electronic Resource
    Electronic Resource
    Quality of life in women with recurrent breast cancer (1999)
    Springer
    Breast cancer research and treatment 54 (1999), S. 47-57 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; cancer recurrence ; psychosocial ; quality of life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Although the psychosocial concomitants of early-stage breast cancer have been well-documented, the relationship between cancer recurrence and quality of life remains less clear. We conducted a prospective, longitudinal study in order to clarify the relationship between recurrent cancer and quality of life, and to determine predictors of quality of life following recurrence. Sixty-nine women with recurrent breast cancer completed questionnaires assessing multiple components of quality of life at three time points: prior to recurrence, immediately after the diagnosis of recurrence, and at follow-up 6 months later. Perceptions of overall quality of life, general health status, emotional, social, and physical functioning were poorer immediately following the diagnosis of recurrence than they had been prior to recurrence. These women also evidenced significant improvement in several domains of quality of life between initial recurrence and follow-up; nonetheless, most areas of quality of life were impaired compared to pre-recurrence. Self-reported physical symptoms were a strong predictor of post-recurrence ratings of overall quality of life. These data suggest that the recurrence of breast cancer is associated with significant changes in quality of life. Quality of life did not progressively deteriorate, however, attesting to the resilience of women coping with this major stressor. These data shed light on issues of potential importance to patients managing this serious illness and may have implications for health-care professionals working with this population.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006172024218
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  • 93
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    Electronic Resource
    Prognosis, treatment, and recurrence of breast cancer for women attending or not attending the Screening Mammography Program of British Columbia (1999)
    Springer
    Breast cancer research and treatment 54 (1999), S. 73-81 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; outcomes ; prognosis ; screening mammography ; treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Breast cancer screening programs have been initiated in many countries in the past decade. To determine the impact of the Screening Mammography Program of British Columbia (SMPBC), disease and treatment outcomes for women with breast cancer diagnosed in BC between 1989 and 1996 were compared on the basis of attendance at the SMPBC. An SMPBC attender was a women diagnosed with breast cancer within three years of an SMPBC screen, regardless whether the cancer was detected as a result of that screen. Of the 13,636 women aged 40–89 years diagnosed with breast cancer in BC during the study period, 2,647 (19.4%) were SMPBC attenders. 73.5% of SMPBC attenders (N=1,946) and 74.2% of non-attenders (N=8,149) were referred to the BC Cancer Agency and had pathology, staging, treatment, and outcome information available. SMPBC attenders compared with non-attenders were more likely to have in situ disease alone, and those with invasive cancers had smaller tumors which were less likely to have grade III histology and less likely to have spread to axillary lymph nodes (all P〈0.001). SMPBC attenders were more likely to be treated with breast conservation and less likely to receive adjuvant chemotherapy or tamoxifen (P 〈 0.001). Log-rank tests showed local (P = 0.017), distant (P 〈 0.001), and overall (P 〈 0.001) disease-free survival were better for SMPBC attenders. These favorable surrogate endpoints suggest that the benefits of breast screening as demonstrated by randomized trials can be translated into community practice by an organized breast screening program.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006152918283
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  • 94
    Electronic Resource
    Electronic Resource
    Sentinel lymphadenectomy in breast cancer: identification of sentinel lymph node and detection of metastases (1999)
    Springer
    Breast cancer research and treatment 53 (1999), S. 97-104 
    Details
    ISSN: 1573-7217
    Keywords: axillary dissection ; breast cancer ; sentinel lymphadenectomy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Sentinel lymphadenectomy is a useful way of assessing axillary status and obviating axillary dissection in patients with node-negative breast cancer. However, controversies remain concerning the optimal method to identify the sentinel lymph node (SLN) and detect micrometastases in this lymph node. We reviewed the literature concerning sentinel lymphadenectomy in breast cancer and reached the following conclusions: (a) A combination of preoperative lymphoscintigraphy with intraoperative dye-guided and gamma probe-guided methods achieves a higher rate of identification of SLN than any of these techniques alone. (b) Immediate and reliable intraoperative assessment of sentinel node status is vital to the technique's success. However, the reliability of sentinel node diagnosis using frozen sections is questionable, because micrometastatic foci cannot always be identified. (c) Hematoxylin and eosin (H&E) staining and/or immunohistochemistry on permanent sections are useful for the detection of micrometastases in the sentinel node. Although a reverse transcriptase–polymerase chain reaction (RT–PCR) method is more sensitive than H&E staining and immunohistochemistry, it would not distinguish benign from malignant epithelial cells in the SLN. Therefore, further study is required before sentinel lymphadenectomy gains general acceptance for patients with primary breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006118827167
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  • 95
    Electronic Resource
    Electronic Resource
    Effect of thermal variables on human breast cancer in cryosurgery (1999)
    Springer
    Breast cancer research and treatment 53 (1999), S. 185-192 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; cryosurgery ; cellular freezing injury ; freezing damage ; surgical oncology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There is a growing interest in the use of cryosurgery to treat breast cancer, following recent breakthroughs in non-invasive imaging and in cryotechnology, as well as the recent success of cryosurgery in treating various types of cancer. However, since haphazard freezing does not guarantee tissue destruction, in order to apply this technique effectively it is essential to determine the thermal parameters that produce complete destruction of malignant tissue. This study seeks to quantitatively identify the relationship between thermal variables and the degree of freezing damage to human breast cancer cells. In order to do this, human breast cancer and normal cells were frozen with controlled thermal parameters using a directional solidification apparatus. Cell viability was determined after thawing using trypan blue, and correlated to the thermal variables used during freezing. Cellular damage is observed to increase with increasing cooling rates, due to the higher probability of intracellular ice formation. A double freeze thaw cycle significantly increases the extent of cell damage, and is sufficient to ensure complete cell destruction at final freezing temperatures of −40°c for a 25°c/min cooling rate, and −20°C for a 50°C/min cooling rate. The correlations between cell death and thermal parameters are qualitatively identical for all the cell types in this study, although there is some variation from one cell type to another in the overall susceptibility to freezing damage. The correlations established in this study can be used to design systematic and optimal breast cryosurgery protocols.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006182618414
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  • 96
    Electronic Resource
    Electronic Resource
    Neo-adjuvant chemotherapy for operable breast cancer induces apoptosis (1999)
    Springer
    Breast cancer research and treatment 53 (1999), S. 263-269 
    Details
    ISSN: 1573-7217
    Keywords: apoptosis ; breast cancer ; neo-adjuvant chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The use of neo-adjuvant chemotherapy (often referred to as pre-operative or primary chemotherapy) represents a major change in the management of breast cancer as a systemic disease. Laboratory studies have shown that many anti-cancer agents with differing modes of action achieve cytotoxic effects by inducing apoptosis. In this study, we investigated the induction of apoptosis by neo-adjuvant chemotherapy in human breast cancer. The aim was to determine whether a correlation existed between post chemotherapy apoptotic index (AI) and clinical response and patients' survival. Our results indicate that apoptosis is induced by neo-adjuvant chemotherapy and that the response is variable. Our data show that post chemotherapy AI correlated with clinical response and increased patient survival, including both relapse (disease) free survival and overall survival. Post-neo-adjuvant chemotherapy AI levels in primary breast cancer may possibly predict an individual patient's overall response.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006194921139
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  • 97
    Electronic Resource
    Electronic Resource
    Prognostic significance of Ki‐67 and topoisomerase IIα expression in infiltrating ductal carcinoma of the breast (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 61-71 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; immunohistochemistry ; Ki‐S4 ; prognosis ; proliferation ; topoisomerase IIα
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To evaluate the prognostic relevance of Ki‐67 and topoisomerase IIα expression in relation to tumor stage, grade, and hormone receptor content, 942 ductal infiltrating carcinomas of the breast were examined by means of the monoclonal antibodies Ki‐S11 (Ki‐67) and Ki‐S4 (topoisomerase IIα). pS2, c‐erbB2, and p53 were additionally considered as prognostic variables. The median follow‐up time was 149 months. Eight‐hundred‐and‐sixty‐three tumors reacted with Ki‐S11 and Ki‐S the labeling indices of the two antigens were closely associated (r=0.93). Both correlated positively with the tumor size, c‐erbB2, and p53 expression, and negatively with patient age, hormone receptor content, and pS2 immunostaining. In the univariate analysis, Ki‐S11 and Ki‐S4 scores, nodal status, tumor size, tumor grade, and progesterone receptor content strongly predicted both overall and metastasis‐free survival (p 〈0.00001). Estrogen receptor status, p53, and c‐erbB2 were of minor significance. Concerning overall survival, multivariate Cox regression analysis selected a Ki‐S4 score 〉25% (p 〈 0.00001) next to the nodal status, and before tumor size, progesterone receptor content, and patient age. Independent predictors of the occurrence of distant metastases were nodal status, Ki‐S4, tumor size, grade 1, and progesterone receptor negativity, in that order. The Ki‐S11 score was of independent prognostic significance only if examined as a continuous variable. We conclude that topoisomerase IIα expression as assessed by monoclonal antibody Ki‐S4 may add valuable information to current prognostic models for breast cancer. Its predictive value appears to be essentially related to the proliferative activity of tumor cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006159016703
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  • 98
    Electronic Resource
    Electronic Resource
    The effect of combining aromatase inhibitors with antiestrogens on tumor growth in a nude mouse model for breast cancer (1999)
    Springer
    Breast cancer research and treatment 57 (1999), S. 183-192 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; nude mice ; aromatase inhibitors ; antiestrogens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have previously established a model for postmenopausal, hormone‐dependent breast cancer in nude mice which is responsive to both antiestrogens and aromatase inhibitors. In this model, MCF‐7 human breast carcinoma cells transfected with the aromatase gene (MCF‐7CA) synthesize sufficient estrogen to form tumors in ovariectomized nude mice. In the present study we used this intratumoral aromatase model to investigate the effects on tumor growth of the new nonsteroidal aromatase inhibitors letrozole (CGS 20,267) and anastrozole (ZD 1033) and the antiestrogens tamoxifen (ICI 47,474) and faslodex (ICI 182,780). Furthermore, we determined whether the inhibition of estrogen synthesis together with inhibition of estrogen action would be more effective in controlling breast tumor growth. The results of our studies indicate that the aromatase inhibitors anastrozole and letrozole, as well as the new pure antiestrogen faslodex, have potent antitumor effects in the mouse model. In the treatment of mice with mammary tumors, letrozole was more effective in suppressing tumor growth than anastrozole. This was consistent with the Ki values of these inhibitors against placental aromatase and the IC50 values in cell culture (MCF‐7CA), which indicated the greater potency of letrozole as an aromatase inhibitor. Letrozole also had greater antitumor effects than tamoxifen and faslodex. The antitumor effect of letrozole was substantial, making it difficult to detect any additional effect on the tumors when letrozole was combined with the antiestrogens. However, the combined treatment of anastrozole + tamoxifen and anastrozole + faslodex also did not increase efficacy compared to the aromatase inhibitor alone. In addition, combining the two antiestrogens did not suppress tumor growth more effectively than faslodex alone. Our results show that treatment with the combinations of aromatase inhibitors with either tamoxifen or faslodex are not more effective in blocking estrogen stimulation of tumor growth than the aromatase inhibitors alone.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006225601046
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  • 99
    Electronic Resource
    Electronic Resource
    5‐HT3 antiemetic therapy for patients with breast cancer (1999)
    Springer
    Breast cancer research and treatment 57 (1999), S. 207-214 
    Details
    ISSN: 1573-7217
    Keywords: antiemetic therapy ; breast cancer ; chemotherapy ; granisetron ; ondansetron ; quality of life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Antiemetic treatment should be considered for breast cancer patients receiving moderately emetogenic chemotherapy. Although the extent of chemotherapy‐induced emesis is largely dependent on the emetogenic potential of the specific agents employed, patient characteristics such as age and sex also contribute. Recent clinical studies show that treatment with the currently available 5‐HT3 antagonists effectively reduces the incidence of chemotherapy‐induced nausea and vomiting and improves quality of life in a substantial number of these patients. A Medline search from 1994 through February 1998 identified clinical trials that included previously untreated breast cancer patients using antiemetic therapy such as granisetron, ondansetron, dolasetron, and metoclopramide. The studies reviewed here indicate that the antiemetic efficacy of 5‐HT3 antagonists is equivalent in previously untreated patients receiving moderately emetogenic chemotherapy for breast cancer, depending on the doses and schedules utilized. In particular, two comparative studies of granisetron and ondansetron with specific data for breast cancer patients showed that both agents eliminate nausea in approximately 50%, and vomiting in 60–70% of these patients, with the higher values observed when steroids were added to the 5‐HT3 receptor antagonist regimen. Although the chemotherapy regimens employed for breast cancer are considered only moderately emetogenic, these regimens account for 60–90% of patients experiencing nausea and vomiting. The most recent clinical studies demonstrate that 5‐HT3 antagonists can significantly reduce the incidence of nausea in breast cancer patients receiving moderately emetogenic chemotherapy and should be employed in this setting.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006233802863
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  • 100
    Electronic Resource
    Electronic Resource
    α2‐Adrenergic effect on human breast cancer MCF‐7 cells (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 41-49 
    Details
    ISSN: 1573-7217
    Keywords: α2‐adrenergic agonists ; α2‐adrenergic antagonists ; α2‐adrenoceptor ; breast cancer ; catecholamines ; human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract (-)Epinephrine (Epi) and –Norepinephrine (NEpi) significantly stimulated tritiated Thymidine incorporation in MCF‐7 cells at concentrations 10–30 pM to 10 nM, with an EC50 of 10 pM for Epi and 14.2 pM for NEpi. To characterize this action, cells were incubated in the presence of NEpi or Epi and different antagonists. The β‐adrenergic antagonist Propanolol showed no effect on the agonist's stimulation, whereas the α‐adrenergic antagonist Phentolamine, reverted it completely at high concentrations (100 μM). The α1‐adrenergic antagonist Prazosin (Pra) acted only at high concentrations, while the α2‐adrenergic antagonist Yohimbine (Yo) reverted the stimulation at an EC50 of 0.11μM. Likewise, when the cells were incubated in the presence of the specific α2‐adrenergic agonist Clonidine (Clo), Thymidine incorporation was significantly stimulated at an EC50 of 0.298 pM. Again, the incubation of the cells in the presence of the α1‐adrenergic antagonist Pra exerted its action at high concentrations, whereas the α2‐adrenergic antagonist Yo showed a clear reversal of the agonist's enhancement at an EC50 of 0.136 μM. Moreover, Clo caused a clear and significant inhibition of stimulated cAMP levels both in the intracellular and the extracellular fractions. Yo showed a complete reversion of cAMP levels to control values in the presence of Clo, while Pra had the opposite effect. These data suggest that the stimulation provoked in Thymidine incorporation by the agonists Epi, NEpi, and Clo is, at least in part, due to an α2‐adrenergic mechanism directly on tumoral cells, and that the effect is coupled with inhibition of cAMP levels, as described for this kind of receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006196308001
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