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  • breast cancer  (139)
  • Neurologie
  • Theoretische Physik
  • Messtechnik
  • Strömungsmechanik
  • Springer  (140)
  • Oxford University Press
  • American Institute of Physics (AIP)
  • 2000-2004  (140)
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Keywords
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  • Springer  (140)
  • Oxford University Press
  • American Institute of Physics (AIP)
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Year
  • 1
    ISSN: 1573-7217
    Keywords: bone metastases ; breast cancer ; clinical course ; localization of metastases ; prognosis ; therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Although metastasis is a frequent event in breast cancer patients, insight into the clinical course, prognosis and therapy with respect to the site of the first metastases has been poor and contradictory in former investigations. Follow-up data from 648 patients with metastatic breast cancer were statistically analyzed. Patients with bone metastases at first relapse had better overall survival (median 71 vs. 48 months; p〈0.001) and survival after first metastases (median 24 vs 12 months; p〈0.001) than patients with visceral metastases at first relapse. Bone was the site of first metastasis in 46%, and 71% of patients with metastatic breast cancer developed bone metastases. The localization of the second metastatic site was of prognostic relevance in patients with first visceral metastases, but not in patients with first bone metastases. The presence of osseous metastases correlated significantly with estrogen and progesterone receptor positivity, tumor grading I/II and S-phase fraction 〈5%. The better prognosis of patients with bone metastases is not determined exclusively by hormone receptor status. The disease is significantly more stable in patients with first bone metastases than in those with first visceral metastases.
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  • 2
    ISSN: 1573-7217
    Keywords: breast cancer ; cellular immunity ; β2-microglobulin ; sIL-2r ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: The association of known prognostic factors with immune cell counts and β2-microglobulin and soluble IL-2 receptor (sIL-2r) serum levels as markers of activation of the immune system was investigated in breastcancer. Methods: Two hundred thirty five operated stage I and II breast cancer patients to receive adjuvant treatment in IBSCG trials were assessed in a cross-sectional study immediately before the first treatment. Leukocytes, lymphocytes and lymphocyte subset counts, β2-microglobulin and sIL-2r serum levels were assessed as immunological parameters. Prognostic factors were tumor load, receptor status, patient characteristics, and contextual factors of the immune assessment (such as time of the day, time since surgery, type of surgery, concomitant medication, co-morbidity). Results: In an operated early stage breast cancer patient population, tumor load was not associated with immune cell counts, β2-microglobulin, or sIL-2r before adjuvant treatment. There was a pattern of association of prognostically favorable factors such as estrogen receptor (ER) positive tumor and older age with higher NK cell counts or with β2-microglobulin or sIL-2r. In addition, immune cell counts and the markers of activation of the immune system were affected by several contextual factors, such as diurnal variability, time since surgery, type of surgery, and the intake of concomitant medication. Conclusions: The association of NK cell counts and β2-microglobulin or sIL-2r serum levels with prognostically favorable factors such as ER positive tumor and older age supports the assumption that the immune system plays a role in the course of early breast cancer. The exact nature of this role requires furtherstudy.
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  • 3
    ISSN: 1573-7217
    Keywords: breast cancer ; bcg-1 ; L19 ; L34 ; MAGE-like ; MLN70 ; subtractive hybridization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A number of approaches have been used to identify genes important in breast cancer. In one approach the genes already shown to be involved in other tumors, such as p53 and Her2neu, were examined. A second approach examined genes detected through genetic screening of families with a high incidence of breast cancer, for example, BRCA-1 and BRCA-2. We used a third approach, subtractive hybridization, to identify and clone genes that were preferentially expressed in breast cancer cells compared to normal mammary epithelium. Instead of analyzing breast cancer cell lines, we examined fresh human breast cancer specimens. By subtracting normal mammary epithelial cDNA from breast cancer cDNA, we were able to clone several genes overexpressed in breast cancer. Two of these genes, L19 and MLN70, were previously reported to be overexpressed in breast cancer. Three of these genes, L19, L34, and MLN70, were localized to a region on chromosome 17 where Her2/neu and BRCA-1 are found. In addition, we isolated a gene we call breast cancer associated gene-1 that was expressed almost exclusively in fresh breast cancer tissue and not in normal mammary epithelium or breast cancer cell lines. We were unable to detect expression of breast cancer associated gene-1 in cell lines from melanoma, renal cell carcinoma, lymphoma, or leukemia. The full-length sequence from two separate breast cancer specimens revealed one amino acid difference compared to the sequence from normal breast epithelial tissue. Further studies are necessary to determine whether these genes contribute to breast cancer development or can be used as therapeutic targets.
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  • 4
    ISSN: 1573-7217
    Keywords: axillary lymphnode metastasis ; breast cancer ; 111In-pentetreotide ; receptor autoradiography ; somatostatin receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We conducted a prospective analysis of somatostatin receptor scintigraphy using 111In radiolabeled pentetreotide, a somatostatin analog, in patients with breast cancer in the aim to visualize the primary tumor and axillary or parasternal metastatic extension because some malignant breast tumors express somatostatin receptors (SS-R) in 50%, approximately. An analysis of SS-R was performed by autoradiography. Patients and methods.Thirteen patients with clinically suspected breast tumors (T1, T2), and at least one palpable axillary node (N1) were included. In vivo planar scintigrams were acquired 1, 4, and 24 h after subcutaneous, then after intravenous injections (24 h delay between injections). Improved 111In-pentetreotide uptake in invaded nodes after subcutaneous injection was hypothesized. Ex vivo scintigrams of surgical specimens were also acquired immediately after tumor resection and axillary dissection. Pathological examination and receptor autoradiography were performed on all surgical specimens. Results.Among 11 pathologically proven malignant tumors (9 ductal and 2 lobular carcinomas), only four were scintigraphically visible although six expressed SS-R receptors in vitro. Among six pathologically proven malignant nodes, four expressed SS-R, including two visualized scintigraphically. Scintigrams acquired after subcutaneous injections were less sensitive than after intravenous injections. There were no false positive. False negatives occurred in cases with small tumors with low-density or heterogeneously distributed SS-R. There was no significant difference by histological type or prognostic factors. Conclusion.Somatostatin receptor scintigraphy does not appear to be sensitive enough to evaluate axillary node extension of breast cancer or even to confirm the presence of tumoral tissue, and this whatever the administration route for 111In-pentetreotide.
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  • 5
    ISSN: 1573-7217
    Keywords: ataxia telangiectasia ; ATM ; breast cancer ; mutation screening
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Based upon the results of several epidemiologic studies, it has been suggested that women who are carriers for a mutation in the ataxia telangiectasia-mutated (ATM) gene are susceptible for the development of breast cancer. Therefore, 37 consecutive breast cancer patients were screened for the presence of a germline ATM mutation using a non-isotopic RNase cleavage-based assay (NIRCA). This paper reports the first use of NIRCA for detection of ATM mutations in breast cancer patients. Using this assay, no ATM mutations were found in our patient population. This result is similar to the findings of other studies that have employed approaches complementary to NIRCA.
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  • 6
    ISSN: 1573-7217
    Keywords: breast cancer ; p21WAF1/CIP1 ; p53 ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract p21WAF1/CIP1 is transcriptionally activated by wt p53 and inhibits G1 associated cyclins, a major mechanism by which p53 inhibits cellular proliferation. Archival breast cancers (798) with a median follow-up of 16.3 years were used to explore the prognostic value of p2l immunohistochemical analyses. p21 immunostaining was detected in the majority (726/798: 91%) of breast cancers as well as adjacent in situ carcinomas (125/170: 74%), hyperplastic lesions (140/349: 40%) and normal breast epithelium adjacent to carcinoma (3/89: 3%). Complete immunonegativity was observed in only 9% of invasive cancers and was associated with p53 immunopositivity (p〈0.05). Univariate analysis of all patients showed that p21 negativity was associated with a longer disease specific survival (relative risk (RR) 1.5). Node positive p21 – patients also showed a longer disease free and disease specific survival as compared to tumor p21+ patients. In node negative patients, p53 positivity but not p21 alone, was significantly associated with a shortened disease free survival (RR = 1.6). Node negative patients who were p53 + p21−, in particular had the shortest disease free survival compared to other p53, p21 subgroups (i.e., p21 negativity was associated with a worse outcome). Multivariate analysis of lymph node negative patients (n〉300) demonstrated that tumor size and tumor grade were independently predictive of outcome, whereas neither p53 nor p21 were significant. For node positive patients, p21 positivity (p=0.05), p53 positivity (p=0.03), a higher number of positive nodes, larger tumor size, steroid receptor negativity, high proliferation rate, and erbB-2 expression were each independently associated with poor outcome. In summary, p21 negativity was inversely correlated with p53 immunopositivity in the majority of cases. p21 negative tumor patients had an improved outcome if they were node positive, whereas p21 status was not significantly associated with survival in node negative patients. This observation may be due to the reported ‘uncoupling of S phase and mitosis’ associated with a loss of p21 expression which may result in enhanced sensitivity to chemotherapy.
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  • 7
    ISSN: 1573-7217
    Keywords: breast cancer ; intravenous digital subtraction angiography ; axillary lymph node metastasis ; neovascularization of lymph nodes ; microvascular density ; antibody to platelet/endothelial cell adhesion molecule
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Accurate predication of axillary node status by non-invasive diagnostic method would be of great value in cases of breast cancer. There have been few reports advocating digital subtraction angiography (DSA) as specifically advantageous for the detection of lymph node metastasis. IV (intravenous)-DSA was carried out on 42 patients with breast carcinoma using a DSA system with a matrix of 1024 × 1024×pixels. When a mass became stained in the axilla, it was considered to be metastatic. An immunohistochemical technique with JC70 antibody to platelet/endothelial cell adhesion molecules was used to evaluate the microvascular density (MVD) of the axillary lymph nodes. IV-DSA achieved a 76.2% sensitivity, 85.7% specificity, and 81.0% accuracy. The average MVD with JC70 antibody was 97.7 ± 44.4 in metastatic and 62.9 ± 23.6 in nonmetastatic nodes. MVD was significantly higher in the cancerous than in the noncancerous regions within lymph nodes. The MVD was 105 ± 38.4 in DSA-N(+) cases and was 57.8 ± 21.9 in DSA-N(−) cases, and the difference was statistically significant. In conclusion, IV-DSA is a useful diagnostic modality for detection of axillary lymph node metastasis. This new modality predicts lymph node status by assessing the neovascularization of the lymph node.
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  • 8
    ISSN: 1573-7217
    Keywords: adhesion ; breast cancer ; disintegrin ; integrins ; invasion ; metastasis ; angiogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report the results of a multidisciplinary study on the inhibitory effect of a snake venom disintegrin, contortrostatin, a 13.5 kDa homodimeric protein isolated from Agkistrodon contortrix contortrix (southern copperhead) venom, on breast cancer progression. We demonstrate that contortrostatin binds to integrins and blocks the adhesion of human breast cancer cells (MDA-MB-435) to extracellular matrix (ECM) proteins including fibronectin and vitronectin, but it has no effect on adhesion of the cells to laminin and Matrigel. Contortrostatin also prevents invasion of MDA-MB-435 cells through an artificial Matrigel basement membrane. Daily local injection of contortrostatin (5 μg per mouse per day) into MDA-MB-435 tumor masses in an orthotopic xenograft nude mouse model inhibits growth of the tumor by 74% (p = 0.0164). More importantly, it reduces the number of pulmonary macro-metastasis of the breast cancer by 68% (p 〈 0.001), and micro-metastasis by 62.4% (p 〈 0.001). Contortrostatin is not cytotoxic to cancer cells, and does not inhibit proliferation of the breast cancer cells in vitro. However, contortrostatin inhibits angiogenesis induced by the breast cancer, as shown by immunohistochemical quantitation of the vascular endothelial cells in tumor tissue removed from the nude mice. We have identified αvβ3, an important integrin mediating cell motility and tumor invasion, as one of the binding sites of contortrostatin on MDA-MB-435 cells. We conclude that contortrostatin blocks αvβ3, and perhaps other integrins, and thus inhibits in vivo progression.
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  • 9
    ISSN: 1573-7217
    Keywords: Bcl-2 ; breast cancer ; chemosensitivity ; HDRA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Programmed cell death is an important determinant of the response to chemotherapy. Among the factors controlling this process, a significant role is played by bcl-2, bax and p53. The in vitro chemosensitivity of the 177 breast carcinomas was assessed by the histoculture drug response assay (HDRA) using mitomycin C (MMC), 5-fluorouracil (5-Fu), adriamycin (ADM), cisplatin (CDDP), and cyclophosphamide (CPA). The susceptibility of Bcl-2-negative tumors to all the drugs killing was significantly higher than that of Bcl-2-positive tumors. No relationship between Bax or p53 immunoreactivity and sensitivity for any of anticancer drugs studied was demonstrated. Immunohistochemical results regarding Bcl-2 are promising in the evaluation of the sensitivity of cancer cells to a series of anticancer drugs and might be therapeutically useful as an indicator of response to adjuvant chemotherapy for breast cancer.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    ISSN: 1573-7217
    Keywords: breast cancer ; prevention ; tamoxifen ; raloxifene ; SERMs ; retinoids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Despite a recent trend toward improvement in the U.S. breast cancer mortality rate, breast cancer incidence (182,800 new cases anticipated in 2000) and mortality figures (over 40,800 anticipated deaths) remain the highest and second highest, respectively, of all cancers in U.S. women. In 1998, the selective-estrogen-receptor-modulator (SERM) tamoxifen achieved positive results in the Breast Cancer Prevention Trial (BCPT), leading to the Food and Drug Administration (FDA) approval of tamoxifen for risk reduction in women at high risk of breast cancer (the historic first FDA approval of a cancer preventive agent). This brought about a paradigm shift in new approaches for controlling breast cancer toward pharmacologic preventive regimens, called chemoprevention. This paper presents a comprehensive clinical review of breast cancer prevention study, highlighting issues of the extensive study of tamoxifen. These issues include the record of primary tamoxifen results in several breast-cancer risk-reduction settings (primary, adjuvant, and ductal carcinoma in situ [DCIS]); critical secondary BCPT risk-benefit findings (including quality of life issues) and their effects on counseling patients on use of tamoxifen for prevention; ethic minorities; optimal tamoxifen dose/duration; and potential impact on mortality and other issues involved with potential net benefit to society. Other breast-cancer chemoprevention issues reviewed here include women at high genetic risk (especially BRCA1 mutation carriers); raloxifene in breast cancer prevention; other SERMs; SERM resistance; and new agents and combinations currently in development. Very recent developments involving PPAR-γ ligands, COX-2 inhibitors, and RXR-ligands are discussed in the section on new drug development.
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  • 11
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 62 (2000), S. 19-33 
    ISSN: 1573-7217
    Keywords: BRCA1 ; BRCA2 ; breast cancer ; familial risk ; risk management
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Women who are members of breast cancer families are at increased risk for breast cancer. The cloning of BRCA1 and BRCA2 has made it possible to identify mutation carriers within some of these families. Management of breast cancer risk in these families, which presents enormous challenges to patients and clinicians, is addressed. Management should begin with a full evaluation of the patient, including construction of a three-generation pedigree, ascertainment of non-genetic factors that may impact on risk, information on previous and current breast health, practice of and attitudes toward screening, and the psychosocial impact of family history on the individual. Patient priorities in risk management should be explicitly reviewed; these may include survival, cancer prevention, breast preservation, optimization of quality of life or minimization of disruption of day-to-day activities. Approaches to risk management involve screening (usually considered the mainstay), anti-estrogens, prophylactic surgery and/or lifestyle modifications. Specific gene therapy may become available in the future. Management decisions should be individualized to reflect risk levels and patient priorities and goals, within bounds that are medically and scientifically reasonable. An explicit examination of different time-frames (1, 5, 10 years) is recommended given the rapid evolution of knowledge in this area.
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  • 12
    ISSN: 1573-7217
    Keywords: breast cancer ; breast conserving surgery ; clinical trial ; celebrity ; consensus statement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background.Three important events in the history of breast cancer treatment occurred between 1983 and 1995: a large clinical trial, first lady Nancy Reagan's choice of mastectomy and the publishing of an NIH consensus statement. Objective.To assess the effects of these events on use of breast conserving surgery (BCS). Research design.Data from the cohort study of the surveillance, epidemiology and end results (SEER) Program from 1983 to 1995 were divided into four periods: Baseline, Trial, Celebrity, and Consensus. Subjects.Of the women, 169,466 diagnosed with early stage breast cancer in nine SEER areas. Measures.Monthly percentages of BCS. Results.A linear regression model generated a separate intercept and slope term for four time periods, adjusting for demographic characteristics of breast cancer patients. For the Baseline, Celebrity and Consensus Periods, slopes indicated an increasing use of BCS which varied between 0.24% and 0.28% per month. Slopes for these three periods were not statistically different (p = 0.120). In contrast, there was no change in use of BCS during the trial period (p = 0.247). We tested the magnitude of discontinuity between periods. At the beginning of the trial, celebrity and consensus periods, there were increases in BCS of 5.54% (p 〈 0.001), −3.55% (p 〈 0.001), and 2.37% (p 〈 0.001), respectively. Conclusions.The use of BCS was substantially affected by the reports of a clinical trial of BCS and by celebrity action. These effects were abrupt but transient. The NIH consensus statement stimulated a small change in use of BCS and may be an important intervention for maintaining the increasing trend in use of BCS since the 1990s.
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  • 13
    ISSN: 1573-7217
    Keywords: breast cancer ; epidermal growth factor receptor ; ErbB-2 receptor ; mitogen-activated protein kinase ; ras
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Genetic ras mutations are infrequent in breast cancer but Ras may be pathologically activated in breast cancer by overexpression of growth factor receptors which signal through Ras. Using a highly sensitive, coupled enzymatic assay, we measured Ras activation in 20 breast cancers, two fibroadenomas, and seven normal breast samples. Ras was highly activated compared to benign tissue in 11 of the 20 cancer; 7 of these 11 cancers expressed both the epidermal growth factor (EGF) and ErbB-2/neu/HER-2 receptors with the remaining four cancers with high Ras activation expressing one of these two receptors. In the other nine cancers, Ras activation was similar to that observed in benign breast tissue with none of these cancers expressing the EGF receptor while one expressed the ErbB-2 receptor. None of the cancers tested had an activating K-ras mutation nor did any of the cancers express a truncated EGF receptor or the c-FMS receptor. The activity of mitogen-activated protein (MAP) kinase was high in the cancers, and reflected the degree of Ras activation. In cultured mammary tumor cell lines, we showed that Ras activation was ligand dependent in cells overexpressing the ErbB-2 receptor. Thus, Ras was abnormally activated in breast cancers overexpressing the EGF and/or ErbB-2 receptors indicating there are sufficient ligands in vivo to activate these receptors, and this work provides a basis for new target-based treatments of this disease.
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  • 14
    ISSN: 1573-7217
    Keywords: axillary dissection ; breast cancer ; nodal metastases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A population-based study was performed to assess the likelihood of axillary lymph node metastases in patients with clinically negative lymph nodes, according to patient age, tumor size and site, estrogen receptor status, histologic type and mode of detection. Data were obtained from the population-based Eindhoven Cancer Registry. During the period 1984–1997, 7680 patients with invasive breast cancer were documented, 6663 of whom underwent axillary dissection. Of the 5125 patients who were known to have clinically negative lymph nodes and underwent axillary dissection, 1748 (34%) had positive lymph nodes at pathological examination. After multivariate analysis, histologic type, tumor size, tumor site and the number of lymph nodes in the axillary specimen remained as independent predictors of the risk of nodal involvement (P 〈 0.001). Lower risks were found for patients with medullary or tubular carcinoma, smaller tumors, a tumor in the medial part of the breast and patients with less than 16 nodes examined. This study gives reliable estimates of the risk of finding positive lymph nodes in patients with a clinically negative axilla. Such information is useful when considering the need for axillary dissection and to predict the risk of a false-negative result when performing sentinel lymph nodebiopsy.
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  • 15
    ISSN: 1573-7217
    Keywords: breast cancer ; paclitaxel ; epirubicin ; cisplatin ; weekly administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose.It has been shown in vitro that both cisplatin and epirubicin increase the antitumor activity of paclitaxel. Weekly administration could give a substantial improvement in the therapeutic index of cisplatin and paclitaxel. This study was aimed at defining the antitumor activity of a weekly cisplatin–epirubicin–paclitaxel (PET) administration in locally advanced or metastatic breast cancer patients. Patients and methods.Sixty-eight breast cancer patients with advanced disease, who had not received prior chemotherapy (except adjuvant), received weekly cisplatin 30 mg/sqm, paclitaxel 120 mg/sqm and epirubicin 50 mg/sqm plus G-CSF (day 3–5), for a maximum of 12 cycles. Thirty-five patients had stage IIIB and 33 stage IV disease (14 with visceral metastases). Results.All patients were evaluable for response on an intent to treat basis. Overall, 21 complete and 38 partial responses have been recorded for an 87% ORR (95% CI = 76–94%). Fourteen CRs and 19 PRs have been registered in the 35 patients with locally advanced disease for a 94% ORR (95% CI = 81–99%) while 7 CRs and 19 PRs were observed in the 33 patients with metastatic disease for a 79% ORR (95% CI–61–91%). Surgery was performed in 33/35 women with locally advanced disease. Four of these patients (11%) showed no invasive cancer on pathologic examination, and in an additional 8 patients tumor 〈 1 cm was found in the breast. Only 4/33 patients who underwent surgery relapsed. The projected one-year RFS was greater than 80%. At an 11-month median follow-up (range, 3–19), 11 patients had progressed and 5 had died among the 33 patients with metastatic disease, the median progression-free survival in this group being 14 months. Severe hematologic toxicity was uncommon, grade 3–4 neutropenia and thrombocytopenia occurring in 32% and 4% of patients, respectively. Only 2 episodes of neutropenic sepsis were registered. Packed red blood cell transfusions were required in 7 patients. Vomiting, diarrhoea, mucositis and skin toxicity were severe in 6%, 9%, 10%, and 9% of patients, respectively. Peripheral neuropathy was observed in 47% of patients. Conclusions.The weekly PET administration is a well tolerated and very effective approach in advanced breast cancer patients. It can produce a 40% clinical complete response rate, with a more than 10% pCR rate in patients with T4 disease, and an about 80% ORR in those with distant metastases. A phase III trial comparing PET with a standard every 3 weeks epirubicin—taxol administration is underway.
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  • 16
    ISSN: 1573-7217
    Keywords: adjuvant chemotherapy ; breast cancer ; quality of life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose.To evaluate the quality of life of breast cancer patients previously treated with adjuvant chemotherapy. Method.Registry data were used to recruit a sample of breast cancer patients (N = 61; mean age = 51.6 years) with no current evidence of disease who had completed adjuvant chemotherapy between 3 and 36 months earlier (average = 15.87 months). In addition, a peer nomination procedure was used to recruit an age-matched comparison group of women with no history of cancer (N = 59; mean age = 51.5 years). Both groups were mailed a survey to complete that included the Medical Outcomes Study Short Form 36 (SF-36) and the Center for Epidemiologic Studies Depression Scale (CES-D). These data were used to test the hypothesis that breast cancer patients previously treated with adjuvant chemotherapy experience impaired quality of life relative to their peers and to identify demographic and medical factors associated with individual differences in patient quality of life. Results.Consistent with predictions, the postchemotherapy group scored poorer than the noncancer comparison group on the CES-D and on six of the eight subscales as well as the physical component summary scale of the SF-36 (p 〈 0.05). With regard to individual differences in patient quality of life, younger age and unmarried status were positively related to poorer mental well-being and greater depressive symptomatology (p 〈 0.05). Time since cancer diagnosis and chemotherapy completion were also positively related to greater depressive symptomatology (p 〈 0.05). In contrast, none of the demographic or medical variables assessed were related to physical well-being (p 〉 0.05). Conclusions.Breast cancer patients appear to experience problems in multiple quality of life domains following the completion of adjuvant chemotherapy treatment. Demographic and medical characteristics explain individual differences in mental but not physical aspects of patient quality of life. These findings demonstrate the need for interventions to improve the quality of life in breast cancer patients previously treated with adjuvant chemotherapy.
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  • 17
    ISSN: 1573-7217
    Keywords: axillary lymph node dissection ; breast cancer ; sentinel lymph node biopsy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Several pilot studies have indicated that SLN biopsy can be used to identify axillary lymph node metastases in patients with breast cancer. To confirm this finding, a multicenter study in a variety of practice settings was performed. A total of 674 patients with breast cancer at five institutions were enrolled. The techniques of SLN identification included the vital dye-guided and the vital dye- and gamma probe-guided methods. The SLN was removed, and complete axillary lymph node dissection (ALND) was performed. SLN and ALND specimens were examined separately. The SLN was successfully identified in 214 (94%) of 227 patients using the combined dye- and gamma probe-guided methods. The SLN was identified in 332 (74%) of 447 patients using vital dye-guided method alone. Patient age of at least 51 years, medially located primary tumor, and clinically positive nodes were correlated with failure to identify the SLN. The accuracy of SLN biopsy for the detection of metastatic disease was 96% (522 of 546), and the sensitivity was 90% (203 of 226). Accuracy of 100% was achieved in the patients with tumors less than 1.6 cm in diameter. All 23 false negative results occurred with larger primary tumors. SLN biopsy can accurately predict the presence or absence of axillary lymph node metastases, particularly in patients with small (≤ 1.5 cm) breast cancers.
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  • 18
    ISSN: 1573-7217
    Keywords: breast cancer ; locally advanced ; neoadjuvant ; chemotherapy ; paclitaxel ; cisplatin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background.In an earlier study, we have demonstrated a high response rate in metastatic breast cancer using paclitaxel (P) and cisplatin (C). A phase II study using the same regimen (PC) has been conducted in locally advanced breast cancer (LABC). Methods.A total of 72 consecutive patients with non-inflammatory LABC (T2 ≥ 4 cm, T3 or T4, N0–N2, M0). Patients were scheduled to receive 3–4 cycles of the neoadjuvant PC (paclitaxel 135 mg/m2 and cisplatin 75 mg/m2 on day 1) every 21 days. Patients were then subjected to surgery and subsequently received 6 cycles of FAC (5-fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2) or 4 cycles of AC (doxorubicin 60 mg/m2, and cyclophosphamide 600 mg/m2). Patients then received radiation therapy, and those with hormone receptor positive tumors were given adjuvant tamoxifen intended for 5 years. Results.The median age was 39 years (range, 24–78). Clinically, 7%, 58%, and 35% of patients had T2 ≥ 4 cm, T3, and T4, respectively. Disease stage at diagnosis was IIB (33%), IIIA (27%), and IIIB (40%). Complete and partial clinical response to PC was demonstrated in 13 (18%), and 52 (72%) patients, respectively. Of those patients with evaluable pathologic response (68 patients), complete pathologic response (pCR) was achieved in 15 (22%) patients. At a median follow-up of 22 (± 3.5) months, 58 (81%) were alive with no recurrence, nine (12%) were alive with evidence of disease, and five (7%) were dead. None of the patients achieving pCR has developed any relapse. The median overall survival has not been reached for all 72 patients with a projected 3-year survival (± SE) of 90% (± 4%). The median progression-free survival (PFS) was 42.1 (± 4.8) months with a projected PFS of 74% ± 7% at 3-years (for 68 patients). Conclusions.PC regimen in LABC produced a high pCR. The contribution of the other added modalities to survival could not be assessed.
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  • 19
    ISSN: 1573-7217
    Keywords: antibody ; breast cancer ; HER-2/neu ; immunity ; ovarian cancer ; T-cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Immunomodulatory strategies, such as antibody therapy and cancer vaccines, are increasingly being considered as potential adjuvant therapies in patients with advanced stage breast cancer to either treat minimal residual disease or prevent relapse. However, little is known concerning the incidence and magnitude of the pre-existent breast cancer specific immune response in this patient population. Using the HER-2/neu oncogenic protein as a model, a well-defined tumor antigen in breast cancer, we questioned whether patients with advanced stage HER-2/neu overexpressing breast and ovarian cancers (III/IV) had evidence of pre-existent immunity to HER-2/neu. Forty-five patients with stage III or IV HER-2/neu overexpressing breast or ovarian cancer were evaluated for HER-2/neu specific T cell and antibody immunity. Patients enrolled had not received immunosuppressive chemotherapy for at least 30 days (median 5 months, range 1–75 months). All patients were documented to be immune competent prior to entry by DTH testing using a skin test anergy battery. Five of 45 patients (11%) were found to have a significant HER-2/neu specific T cell response as defined by a stimulation index ≥ 2.0 (range 2.0–7.9). None of eight patients who were HLA-A2 had a detectable IFNγ secreting T-cell precursor frequency to a well-defined HER-2/neu HLA-A2 T cell epitope, p369-377. Three of 45 patients (7%) had detectable HER-2/neu specific IgG antibodies, range 1.2–8.9 μg/ml. These findings suggest that patients with advanced stage HER-2/neu overexpressing breast and ovarian cancer can mount a T cell and/or antibody immune response to their tumor. However, in the case of the HER-2/neu antigen, the pre-existent tumor specific immune response is found only in a minority of patients.
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  • 20
    ISSN: 1573-7217
    Keywords: feedback mechanisms ; paracrine regulation ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Breast function and development are controlled by a variety of both local and systemic signals. Many of these signals are exerted by hormones and cytokines which are believed to be effectors in autoregulatory feedback loops. Recent studies have also suggested the involvement of such mechanisms in human breast cancer. For example, the disruption of a negative feedback system by malignant transformation can result in the loss of growth control or in increased malignant behavior of tumor cells. Conversely, pathological positive feedback loops can develop that enhance tumor growth and invasion by excessive release of stimulatory factors. These loops are often located at the site of tumor invasion and involve stromal–epithelial interactions. They can be composed of mutually stimulating or inhibiting cytokines and may include locally expressed sex steroids. Although most studies have concentrated on cell–cell interactions at the site of the primary tumor, a number of observations indicate their importance in metastases as well. A thorough analysis of the regulatory mechansims within a malignant tumor is essential for the understanding of its unique behavior and for the investigation of more specific breast cancer therapies.
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  • 21
    ISSN: 1573-7217
    Keywords: breast cancer ; database ; prognosis ; Taiwan ; young age
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Between April 1990 and December 1997, 811 consecutive patients with 830 newly diagnosed breast cancers having their primary treatments in our institution were included in this study. Sixty three percent of breast cancer patients were premenopausal. The early-onset breast cancer (age ≤ 40) composed 29.3% of all patients. The five-year survival rate of all patients was 80.4% (95% confidence interval [CI], 76.2–84.6%). The five-year overall survival rate for stage 0 was 95.7% (95% CI, 87.3–100%), stage I, 93.9% (95% CI, 88.9–98.9%), stage II, 88.5% (95% CI, 82.0–95.1%), stage III, 65.0% (95% CI, 54.0–75.9%), and stage IV, 18.5% (95% CI, 3.4–33.7%). Multivariate analysis of primary operable breast cancer revealed that axillary lymph node involvement, high nuclear grade and early-onset breast cancer (age ≤ 40) were poor prognostic factors. The early-onset breast cancer had a more aggressive clinical behavior than that of the older age group, their five-year disease-free survival rates for stage I, stage II and stage III diseases being only 64.7%, 66.5%, and 43.3%, respectively. In these patients the only meaningful prognostic factor was extensive axillary lymph node metastasis (≥10). In summary, breast cancer patients in Taiwan tend to be younger than their counterpart in western countries. The early-onset breast cancer had poorer prognostic features for all stages comparing to the older age group. Standard pathologic factors are not good predictors of their outcome. For these patients new biologic markers need to be sought to distinguish between high and low risk and the treatment strategy for them should be guided by the aggressive characteristics of the disease.
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  • 22
    ISSN: 1573-7217
    Keywords: breast cancer ; cholesterol ; triglycerides ; tamoxifen ; toremifene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Tamoxifen decreases serum cholesterol (S-cholesterol) level about 10% and low-density lipoprotein cholesterol (S-LDL) 15–20%, but in most studies it has increased serum triglyceride levels and had little effect on serum high-density cholesterol (S-HDL). The effect of another antiestrogen, toremifene, on the serum lipid profile has not been completely studied. We monitored serum lipid levels longitudinally in 141 axillary node-positive postmenopausal breast cancer patients who received randomly either 40 mg toremifene or 20 mg tamoxifen as adjuvant therapy for 36 months, and in 34 postmenopausal women who received no adjuvant systemic therapy after surgery for axillary node-negative breast cancer. No significant differences were found between the drugs in their effects on S-cholesterol, LDL, HDL, or triglyceride levels, or on the cholesterol-to-HDL or LDL-to-HDL ratios. For both drugs the S-cholesterol and S-LDL absolute lowering effect was the greater the higher the pretreatment level. For a patient with a median pretreatment value, toremifene decreased S-cholesterol 6% and tamoxifen 13%, and S-LDL decreased by 13% and 23%, respectively, at 6 months of therapy. Six months after stopping three-year antiestrogen therapy S- cholesterol and S-LDL levels had returned to the pretreatment levels. In conclusion, we found no major differences between 40 mg toremifene and 20 mg of tamoxifen in their effect on the serum lipid levels, which return to the pretreatment levels within 6 months after cessation of therapy.
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  • 23
    ISSN: 1573-7217
    Keywords: antisense oligodeoxynucleotides ; antineoplastic agents ; apoptosis ; Bcl-2 ; breast cancer ; chemosensitization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have investigated the effects of transient Bcl-2 down-regulation induced by the Bcl-2 antisense oligodeoxynucleotide (ODN) G3139 (Genta Incorporated) in high Bcl-2 protein expressing, estrogen receptor (ER) positive MCF-7 and low Bcl-2 expressing, ER negative MDA435/LCC6 human breast cancer cells. Treatment with Bcl-2 antisense ODN in vitro caused 〉 80% reduction of Bcl-2 protein levels in a sequence specific manner for both cell lines. Maximum mRNA reduction was achieved within 24 h of the first antisense ODN exposure whereas full protein down-regulation required antisense exposure over 48 h. This Bcl-2 reduction was associated with 80–95% loss of viable cells compared to untreated cells. Similar cytotoxic effects were observed in both cell lines despite a nine-fold intrinsic difference in Bcl-2 protein expression suggesting that the relative degree of down-regulation of Bcl-2 is more important than the absolute reduction. Cell death associated with G3139 exposure exhibited properties indicative of apoptosis such as mitochondrial membrane depolarization and caspase activation. Combined treatment with G3139 and cytotoxic agents resulted in additive cytotoxicity in both cell lines. However, under most conditions studied, the direct cytotoxic activity of G3139 antisense was not synergistic with the cytotoxic agents. These results suggest that while Bcl-2 clearly constitutes an attractive therapeutic target due to its role in regulating apoptosis in breast cancer cells, additional mechanisms are important in the control of apoptosis arising from exposure to anticancer agents in vitro.
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  • 24
    ISSN: 1573-7225
    Keywords: breast cancer ; endometrial cancer ; fertility drugs ; infertility ; melanoma ; ovarian cancer ; thyroid cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: Over the past decades the use of fertility drugs (FDs) has greatly increased. Recently, the possible association between the use of FDs and risk of cancer has aroused great concern. In this paper, we critically review the available epidemiologic studies. Methods: We identified papers published between 1966 and 1999 that examined FDs and specific causes of subfertility in relation to the risks of cancers of the ovary, breast, endometrium and thyroid, and melanoma. Results: Although present insights into the pathogenesis of hormone-related malignancies suggest a possible association between the use of FDs and the risk of specific cancers, this has not been convincingly demonstrated in epidemiologic studies. With regard to cancer risk in relation to the cause of subfertility, the only consistent association observed is an increased risk of endometrial cancer for women with subfertility due to hormonal disorders. While positive findings in some studies on FDs and ovarian cancer risk have aroused serious concern, the associations observed in most of these reports appear to be due to bias or chance rather than being causal. The most important sources of bias are inadequate confounder control for both parity and causes of subfertility. Conclusions: To discriminate between the possible carcinogenic effects of various ovulation induction regimens, subfertility disorders, and reproductive characteristics associated with subfertility, future studies should include large populations of subfertile women with sufficient follow-up time. In such cohort studies the cause of subfertility should be measured adequately (based on medical records) and information about reproductive characteristics should be collected for all cohort members. Such studies should also include a group of subfertile women with an indication for FD use but not so treated.
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  • 25
    ISSN: 1573-7225
    Keywords: breast cancer ; colon cancer ; lung cancer ; neoplasm ; prostate cancer ; surveillance ; treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: At a time when the population is aging and medical practices are rapidly changing, ongoing surveillance of surgical treatments for cancer is valuable for health services planning. Methods: We used data from the National Hospital Discharge Survey for patients with discharge diagnoses of lung, prostate, female breast, and colorectal cancer during 1988–95 to estimate population-based rates and numbers of inpatient surgical procedures. Results: In 1988–91, rates of lobectomy for lung cancer were significantly higher in males than females. By 1994–95, the male/female differences had largely disappeared due to increasing trends among females and decreasing trends among males. During 1988–95, surgeries on the large intestine for colorectal cancer, including right hemicolectomy and sigmoidectomy, decreased significantly, as did abdominoperineal resections of the rectum. Anterior resections of the rectum increased significantly. Radical prostatectomies for prostate cancer increased from 34,000 in 1988–89 to 104,000 in 1992–93 and then decreased to 87,000 in 1994–95; rates followed a similar pattern. Finally, the number and rates of inpatient mastectomies for female breast cancer decreased over the study period (from 219,000 to 180,000 and from 78.8 to 61.5 per 100,000, respectively). Conclusion: These trends in inpatient surgeries for the major cancers in the US probably reflect changes in disease occurrence and modified treatment recommendations.
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  • 26
    ISSN: 1573-7225
    Keywords: breast cancer ; insulin growth factor I ; leptin ; postmenopause ; premenopause
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objectives: Because both breast cancer and the hormone leptin are associated with obesity and reproductive phenomena in women, we have examined whether there is a relationship between leptin and breast cancer among premenopausal and postmenopausal women. We have also evaluated in this dataset the association of IGF-I with breast cancer. Methods: Seventy-five cases, diagnosed during mammographic screening, with incident breast cancer were matched for age and type of permanent residence with seventy-five controls from those screened negative in the same study base. Results: There was no evidence for an association between IGF-I and either premenopausal or postmenopausal breast cancer risk or between leptin and postmenopausal breast cancer. Among premenopausal women, however, there was a strong and statistically significant inverse association of leptin with breast cancer. Conclusion: We did not confirm the positive association, reported from other investigations, of IGF-I with premenopausal breast cancer risk. We have found evidence, however, that leptin may be inversely related to breast cancer risk among premenopausal women. The latter finding is not biologically implausible and deserves to be examined in additional datasets.
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  • 27
    ISSN: 1573-7225
    Keywords: abortion ; breast cancer ; pregnancy ; women
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective:Previous studies of induced abortion and breast cancer may have been limited by differential reporting of abortion history. We conducted a population-based case–control study to evaluate abortion (both induced and spontaneous) and breast cancer risk. Methods:All study subjects were aged 20–69 years and members of Group Health Cooperative of Puget Sound (GHC). Incident invasive breast cancer cases (n = 138) were identified from the linkage between the GHC enrollment file and the Seattle–Puget Sound SEER Cancer Registry. Controls (n = 252) were randomly selected from GHC enrollment files and matched to cases on age and enrollment period. All subjects had to have been enrolled at GHC for the 2 years preceding diagnosis (cases) or reference (controls) date. The unified medical record of each case was abstracted for pregnancy history, including prior induced and spontaneous abortions, menopause status, height and weight, screening practices, and other risk factors. Results:Compared to all women who had never had an induced abortion, the multivariate adjusted relative risk of breast cancer in women with an induced abortion was 0.9 (95% confidence interval 0.5–1.6). This risk was similar in parous women, and nulliparous women. There was no association between spontaneous abortion and breast cancer risk. Conclusions:These results do not support a relation between induced abortion and breast cancer incidence.
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  • 28
    ISSN: 1573-7373
    Keywords: choroidal metastasis ; leptomeningeal carcinomatosis ; breast cancer ; docetaxel ; mitoxantrone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Choroidal metastases from breast cancer represent an unusual metastatic presentation that has been traditionally treated with radiation therapy. Herein, we report a case of metastatic breast cancer presenting with pulmonary, cutaneous, lymph node and symptomatic choroidal metastases treated with systemic combination chemotherapy incorporating docetaxel and mitoxantrone without induction or consolidation radiation therapy to control visual symptoms from choroidal metastases. The patient experienced a durable complete remission in all metastatic sites that was maintained for 21 months since the initiation of chemotherapy, afterwhich she developed isolated leptomeningeal carcinomatosis managed successfully with intensive intrathecal methotrexate and whole brain irradiation leading to a new complete remission maintained until this report; 11 months after its presentation. This is the first case to our knowledge reporting complete regression of choroidal metastases with docetaxel-based chemotherapy as the only treatment modality and subsequent isolated leptomeningeal carcinomatosis recurrence.
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  • 29
    ISSN: 1573-7276
    Keywords: breast cancer ; cell motility ; KGF ; metastasis ; MCF-7 ; T-47D ; ZR-75-1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Endogenous growth factors and cytokines are known to have a major influence on the progression, motility and invasiveness of tumor cells. We have reported previously that conditioned media from mouse fibroblasts increases the motility of breast cancer cells. Further, we determined that keratinocyte growth factor (KGF) was an active factor from mouse fibroblasts responsible for most of the motility response in breast cancer cells. The present study examined the effect of human KGF on the motility of estrogen receptor (ER)-positive and ER-negative human breast cancer cell lines in culture using time-lapse videomicroscopy to quantify cell motility. In the present study we observed that recombinant human KGF enhanced several parameters of cellular motility in ER-positive cells but not in ER-negative cell lines. Further, we observed that the level of KGF receptor (KGFR) expression in ER-positive cells was much greater than in the ER-negative cell lines. The motility response to KGF was found to be both dose-and time-dependent. Of the three ER-positive breast cancer cell lines tested, MCF-7 cells were the most responsive to KGF stimulation. Finally, MCF-7 cells grown in estrogen-depleted media did not respond to KGF. These results suggest that KGF from stromal tissue surrounding a primary tumor mass can enhance tumor cell motility and may be an early signal in the progression of breast cancer cells to a more motile and metastatic phenotype. Thus, KGF, KGFR and/or the KGF signaling pathway may be important therapeutic targets for the treatment or prevention of breast cancer metastasis.
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  • 30
    ISSN: 1573-7276
    Keywords: BRCA1 ; breast cancer ; chemically modified tetracycline ; E-cadherin/catenin ; invasion ; migration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chemically modified tetracyclines (CMTs) are promising anti-cancer agents. In this study, we found that CMT-3 and CMT-8 showed dose-dependent cytotoxicities in MDA-MB-468 human breast cancer cells. Moreover, both CMT-3 and CMT-8 significantly inhibited in vitro cell migration and invasion at non-cytotoxic concentrations. Anti-invasion and migration potentials of the CMTs were associated with an increased expression of E-cadherin/catenins (α, β and γ-catenin) and tumor suppressor BRCA1. In addition, CMT-3 and CMT-8 abolished or reduced spontaneous and HGF/SF-induced cell invasion and migration in U-373 MG human glioblastoma cells. Our current finding is the first demonstration that CMT-3 and CMT-8 can activate the function of invasion suppressor molecules associated with the suppression of breast cancer cell invasion and migration. Thus, clinical application of CMTs may provide potential benefit for suppression of breast cancer growth, invasion and metastasis.
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  • 31
    ISSN: 1573-7039
    Keywords: breast cancer ; pathology atlas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This article illustrates the most common benign and malignant lesions in the breast, and is intended for the biologist working in the area of breast cancer and breast biology, not for the practicing pathologist. The atlas covers benign proliferative lesions, atypical lesions, variants of in situ cancer, the main types of invasive cancers, spindle cell lesions, and examples of vascular and lymphatic spread. Some entities are included to illustrate a point of particular relevance to the biology and histogenesis of the lesions. Some controversial diagnostic areas are considered, along with the relative risk of developing breast cancer associated with some of the proliferative lesions. The content of this atlas should be read in conjunction with the companion article by Howard and Gusterson in this issue. Their article covers the cellular origin of epithelial and stromal tumors and presents a description of some of the common benign proliferative lesions that are considered to be components of the normal spectrum of changes seen at postmortem or in biopsies.
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  • 32
    ISSN: 1573-7039
    Keywords: Human ; breast cancer ; premalignant
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Most human invasive breast cancers (IBCs)4 arise from preexisting benign lesions. There are many types of benign lesions in the human breast and only a few appear to have significant premalignant potential (atypical hyperplasias and in situ carcinomas). These lesions are relatively common and only a small proportion progress to IBC. They are currently defined by their histological features and their prognosis is imprecisely estimated from indirect evidence based on epidemiological studies. Although lesions within specific categories look alike, they must possess morphologically silent biological differences motivating some to remain stable and others to progress. Understanding the biological changes responsible for the development and progression of premalignant disease is a very active area of medical research. Progress in this area may provide new opportunities for breast cancer prevention by providing strategies to treat premalignant lesions before they develop or become cancerous. A large number of biological features have been evaluated in this setting during the past decade. This review discusses a few features that appear to be particularly important and have been studied in a relatively comprehensive manner.
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  • 33
    ISSN: 1573-7217
    Keywords: breast cancer ; prostate-specific antigen ; prognostic indicators ; tumor markers ; breast cyst ; benign breast disease ; molecular forms of prostate-specific antigen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Although prostate-specific antigen (PSA) is the most valuable tumor marker for the diagnosis and management of prostate carcinoma, it is widely accepted that PSA is not prostate specific. Numerous studies have shown that PSA is present in some female hormonally regulated tissues, principally the breast and its secretions. In this review, we summarize the findings of PSA in the breast, and focus on its potential for clinical applications in breast disease. PSA is produced by the majority of breast tumors and is a favorable indicator of prognosis in breast cancer. Low levels of PSA are released into the female circulation, and while the level of serum PSA is elevated in both benign and malignant breast disease, the molecular form of circulating PSA differs between women with and without breast cancer. These findings indicate that PSA may have potential diagnostic utility in breast cancer. PSA may also have a clinical application in benign breast disease, as both the level and molecular form of PSA differ between Type I and II breast cysts. High levels of PSA have been reported in nipple aspirate fluid (NAF) and recent studies have shown that the concentration of PSA in NAF is inversely related to breast cancer risk, indicating that NAF PSA may represent a clinical tool for breast cancer risk assessment. Thus, PSA represents a marker with numerous potential clinical applications as a diagnostic and/or prognostic tool in breast disease.
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  • 34
    ISSN: 1573-7217
    Keywords: breast cancer ; lobular ; ductal ; conservative surgery ; radiation therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The role of conservative surgery and radiation therapy (CS and RT) in the treatment of patients with infiltrating ductal carcinoma is well established. However, the efficacy of CS and RT for patients with infiltrating lobular carcinoma is less well documented. The goal of this study was to examine treatment outcome after CS and RT for patients with infiltrating lobular carcinoma and to compare the results to those of patients with infiltrating ductal carcinoma and patients with mixed ductal–lobular histology. Methods: Between 1970 and 1986, 1624 patients with Stage I or II invasive breast cancer were treated with CS and RT consisting of a complete gross excision of the tumor and ≥6000 cGy to the primary site. Slides were available for review for 1337 of these patients (82%). Of these, 93 had infiltrating lobular carcinoma, 1089 had infiltrating ductal carcinoma, and 59 had tumors with mixed ductal and lobular feature these patients constitute the study population. The median follow-up time for surviving patients was 133 months. A comprehensive list of clinical and pathologic features was evaluated for all patients. Additional histologic features assessed for patients with infiltrating lobular carcinoma included histologic subtype, multifocal invasion, stromal desmoplasia, and the presence of signet ring cells. Results: Five and 10-year crude results by site of first failure were similar for patients with infiltrating lobular, infiltrating ductal, and mixed histology. In particular, the 10-year crude local recurrence rates were 15%, 13%, and l3% for patients with infiltrating lobular, infiltrating ductal, and mixed histology, respectively. Ten-year distant/regional recurrence rates were 22%, 23%, and 20% for the three groups, respectively. In addition, the 10-year crude contralateral breast cancer rates were 4%, 13% and 6% for patients with infiltrating lobular, infiltrating ductal and mixed histology, respectively. In a multiple regression analysis which included established prognostic factors, histologic type was not significantly associated with either survival or time to recurrence. Conclusions: Patients with infiltrating lobular carcinoma have a similar outcome following CS and RT to patients with infiltrating ductal carcinoma and to patients with tumors that have mixed ductal and lobular features. We conclude that the presence of infiltrating lobular histology should not influence decisions regarding local therapy in patients with Stage I and II breast cancer.
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  • 35
    ISSN: 1573-7217
    Keywords: breast cancer ; epirubicin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to better explore the toxicity and the activity of high dose epirubicin (120 mg/m2, 3 weeks) we analyzed a population of 127 metastatic breast cancer patients, treated in a randomized clinical trial conducted to evaluate the cardioprotective effect of dexrazoxane against epirubicin induced cardiotoxicity. All the patients had a diagnosis of metastatic breast cancer, an ECOG performance status ≥2 and normal hematologic, renal, hepatic and cardiac function. No prior adjuvant chemotherapy including anthracycline was allowed. Epirubicin was given at the dose of 120 mg/m2 i.v. bolus every 3 weeks. One hundred twenty five patients were evaluable for toxicity and response. Seventeen patients (11%) had a complete response and 47 patients (37%) a partial response, for an overall response rate of 48%. The median progression free and overall survivals were 8.3 months and 18.3 months, respectively. Grade 3 and 4 leukopenia were observed in 8% and 7% of the patients, respectively. The most frequent nonhematological grade 3 toxicities were alopecia (87%), nausea and vomiting (16%), and mucositis (8%). Cardiotoxicity, defined as occurrence of congestive heart failure, decrease in resting left ventricular ejection fraction (L-VEF) to ≥45, or 20 EF units decrease from baseline L-VEF, was observed in 19% of the patients, after a median cumulative dose of epirubicin of 720 mg/m2 (range 120–1440). This study confirms in a large series of patients the activity of high dose epirubicin; however, the high incidence of cardiotoxicity requires a careful evaluation of cardiac risk factors before treatment.
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  • 36
    ISSN: 1573-7217
    Keywords: breast cancer ; bromodeoxyuridine ; Ki-67 ; nodes ; survival ; S-phase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Proliferation indices are intended to help patients and clinicians make treatment decisions. We have previously demonstrated that a proliferation index based on in vivo labeling of S-phase cells with bromodeoxyuridine (BrdUrd) correlates with Ki-67 labeling index (LI). We now compare the prognostic value of these indices. With written consent, we gave 129 women with biopsy confirmed breast cancer 200 mg/M2 BrdUrd during 30 min immediately preceding surgery. We used IU-4 anti BrdUrd antibody to count the immunohistochemical labeling index (LI) of DNA-incorporated BrdUrd in 2,000 cells and MIB-1 to count Ki-67 (118 cases). Patients received standard surgical and adjuvant treatment. No patients were lost to follow-up and patients were followed a minimum of 2 (median 5.1) years. We compared survival and recurrence in tumors with high vs low labeling indices. We found that women in the low BrdUrd LI group had better disease free survival (92% vs 67% 5-yr DFS p = 0.001) and overall survival (94% vs 70% 5-yr OS, p = 0.0001) than those with a high LI. In comparison, a low Ki-67 index predicted better OS (87% vs 80% 5-yr OS, p = 0.020) and a trend for better DFS (84% vs 72% DFS p = 0.055). The apparent superiority of BrdUrd LI over Ki-67 LI is likely due to chance (p = 0.18). In multivariate survival analyses we found that BrdUrd LI proliferative index significantly improves prediction of DFS or OS even when node status, age or tumor size is in the model. We conclude that markers of proliferation are useful adjuncts in predicting patient prognosis.
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  • 37
    ISSN: 1573-7217
    Keywords: breast cancer ; metastasis ; liver metastasis ; surgical procedure ; hepatectomy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have performed a retrospective study to evaluate whether surgical treatment is beneficial in patients with hepatic metastases from breast cancer. Between September 1985 and September 1998, 25 patients with hepatic metastases (14 solitary and 11 multiple), eight of whom had extrahepatic metastases, underwent hepatectomy. All of the detectable liver metastasis were resected in all of the cases. There were no severe postoperative complications. All but one of the patients received adjunctive polychemotherapy after the hepatectomy. After the hepatectomy, recurrent tumors were detected in 18 of the patients, being located in the liver in 12 (67%) of them. Overall, however, hepatectomy ensured that the liver was clinically recurrence-free for a median of 24 months (range 2–132 months). Eleven patients died of recurrent tumors, two died of other causes and the remaining 12 are currently alive. The 2- and 5-year cumulative survival rates after hepatectomy were 71% and 27%, respectively, and the median survival duration was 34.3±3.2 months, much better than the period of 8.5 months for another series of patients treated with standard or non-surgical therapies at our institution. The number and the size of hepatic metastases, the interval between treatment of the primary lesion and hepatectomy, and the existence of extrahepatic metastasis were not adverse prognostic factors. In conclusion, our data, although limited and highly selective, suggest that surgical treatment of hepatic metastases from breast cancer may prolong survival in certain subgroups of patients to a greater extent than standard or non-surgical therapies.
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  • 38
    ISSN: 1573-7217
    Keywords: adjuvant chemotherapy ; breast cancer ; mastectomy ; reconstruction ; skin expander-toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. Immediate breast reconstruction (IBR) by means of skin expander is currently one of the most widely used methods of breast reconstruction in mastectomized patients. However, given that many breast cancer patients usually receive adjuvant chemotherapy, the adoption of IBR raises new questions concerning possible cumulative toxicity. The present study reports our experience in the use of concurrent adjuvant chemotherapy and immediate breast reconstruction with skin expander after mastectomy for breast cancer and the acute cumulative toxicity of the treatments. Methods. We evaluated a consecutive series of 52 breast cancer patients who have received IBR by skin expander after radical mastectomy and adjuvant chemotherapy concurrently during skin expansion between 1995 and 1998 (IBR/CT group). We identified two series of control patients treated during the same period: 51 consecutive patients undergoing radical mastectomy and IBR without adjuvant chemotherapy (IBR group) and 63 consecutive patients undergoing radical mastectomy and adjuvant chemotherapy without IBR (CT group). For each patient, we evaluated the incidence of surgical complications and chemotherapy's side effects and dose intensity. Results. The interval between surgery and the start of expander inflation was similar in IBR/CT (range 0–19, median 5 days) and IBR groups (range 0–40, median 5 days) and the timing of inflation was not influenced by chemotherapy. The overall incidence of surgical complications in patients undergoing IBR was low: seroma in eight cases, infection in one, skin necrosis in one, expander rupture in two and erythema in three. There were no statistically significant differences in the distribution of complications between the IBR/CT and IBR groups. The dose intensity of chemotherapy was similar between IBR/CT and CT groups, with a median dose intensity of 96% and 95% of the projected dose, respectively. The only statistically significant difference in terms of chemotherapy side effects (p=0.03) was that stomatitis was more frequent and intense in the CT than in the IBR/CT group. Conclusions. Concurrent treatment with IBR and adjuvant chemotherapy appears feasible and safe, it does not increase acute surgical complications or chemotherapy side effects, and does not require any changes in dose intensity or the timing of inflation.
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  • 39
    ISSN: 1573-7217
    Keywords: breast cancer ; cell-mediated immunity ; lymphocyte blastogenesis assay ; prognostic indicators ; tumor-associated antigens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cell-mediated immune (CMI) responses to tumor-associated antigens (TAA) in the early postoperative period were examined for correlations with disease recurrence and survival in a 13-year-prospective study of 77 stage 1 and 2 breast cancer patients treated with modified radical or radical mastectomy alone. Among the 21 patients who had positive lymphoproliferative tests using patients' peripheral blood mononuclear cells and autologous TAA of breast cancer cells, only one died from metastatic disease (5%). Among the 56 patients who had a negative test, 23 died from metastatic disease (41%). This difference is statistically significant (p = 0.002) Three other risk factors including tumor size, nodal status and cell differentiation patterns were also analyzed. When these three clinical-pathologic criteria were analyzed individually, none reliably predicted disease recurrence and survival. Nodal status was the most predictive clinical-pathologic risk factor, but was not significant (p = 0.089). The results of this study demonstrate the detection of CMI responses against autologous TAA by lymphoproliferative assays identifies a sub-set of stage 1 and 2 breast cancer patients who are at minimal risk of developing metastatic disease. This testing also identifies immunologically unreactive patients who are at risk for disease recurrence.
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  • 40
    ISSN: 1573-7217
    Keywords: breast cancer ; cancer screening ; compression ; mammography ; pain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of this study was to evaluate the pain experience of women during mammography for breast cancer screening. Possible associations with personal and medical history, sociodemographics and/or situational factors were studied. It was also investigated whether this pain influenced the intention to return for future breast cancer screening. In the Netherlands, women between 50–75 years are invited for screening every two years. A total of 1200 participants were asked to fill up a questionnaire. The response rate was 79.5% (n = 954), and 945 questionnaires contained adequate information for analyses. A total of 689 women (72.9%) described mammography as mild to severely painful. In this group, compared to the group that reported no pain, the following factors occurred significantly more often: sensitive breasts (P = 0.001), family history of breast diseases (P = 0.017), expected pain based on former mammography (P = 0.001), high education (P = 0.008), anxiety (P = 0.001), breast sensitivity in last three days (P = 0.001), insufficient attention of technologist (P = 0.001). Other factors like age, hormonal status, breast size and hormone use were not associated with the pain experienced. Thirty-two women (3.3%) indicated that they would not attend further screening, 25 (2.6%) reported that the pain might deter them, six women (0.6%) had other reasons, one woman (0.1%) was sure not to come because of severe pain. In conclusion, a large majority of women attending breast cancer screening describes mammography as painful (72.9%). Factors associated with pain were described. Relatively few women (2.7%) indicated that the pain might deter them from future mammography. Recommendations are given to reduce the pain experienced during screening mammography.
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  • 41
    ISSN: 1573-7217
    Keywords: adjustment disorders ; breast cancer ; first recurrence ; major depressive disorder ; psychological distress
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objectives: To investigate the prevalence of, and risk factors for psychological distress following first recurrences of breast cancer. Patients and methods: The sample was drawn consecutively from the inpatient and outpatient populations of the National Cancer Center Hospital in Japan during an 18-month period from July 1996 to December 1997. Of the 56 eligible patients, 55 women aged 30–73 year with recurrent breast cancer participated in the study. The prevalence of psychological distress, including major depressive disorder and adjustment disorders was evaluated according to the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Third edition-revised (DSM-III-R). Risk factors for psychological distress were analyzed with a logistic regression model. Results: Of the 55 subjects, 42 met the DSM-III-R criteria for major depressive disorder or adjustment disorders. Major depressive disorder was seen in 4 (7%), and adjustment disorders in 19 (35%). Logistic regression analysis showed that a disease-free interval of less than 24 months significantly predicted a diagnosis of major depressive disorder or adjustment disorders (odds ratio 5.28, 95% confidence interval; 1.28–21.8, p=0.02). Conclusions: These results suggest that it is important for all oncology staff to pay careful attention to the psychological health of patients who have been informed of their cancer recurrence, and that some psychosocial intervention is necessary for preventing distress in patients facing early recurrence.
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  • 42
    ISSN: 1573-7217
    Keywords: breast cancer ; cell cycle ; ductal ; histologic subtypes ; lobular
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Infiltrating lobular carcinoma (ILC) and infiltrating ductal carcinoma (IDC) are similar in many respects and their histologic features occasionally overlap. Despite the many similarities, some clinical follow-up data and the patterns of metastasis suggest that ILC and IDC are biologically distinct. Unfortunately, most breast cancer research has focused almost exclusively on the ductal subtype or has not stressed the biologic or molecular genetic distinctions between breast carcinoma subtypes. Several reports have suggested the possibility that ILCs and IDCs differ with respect to expression of antigens involved in proliferation and cell cycle regulation. Therefore, we undertook an immunohistochemical evaluation of cell cycle related antigens in ILCs, including histologic variants thought to represent aggressive neoplasms, and IDCs matched for histologic grade (Modified Bloom–Richardson Grade I). We believe that different antigent expression profiles could elucidate the biological distinctiveness of breast carcinoma subtypes and possibly provide diagnostically relevant information. We studied the expression of the following antigents in 28 archived, formalin-fixed ILCs and 34 well-differentiated IDCs: estrogen receptor (ER), progesterone receptor (PR), Her 2-neu, mib-1, cyclin D1, p27, p53, mdm-2 and bcl-2. 94% of ILCs and 100% of IDCs expressed ER; 75% of ILCs and 76% of IDCs expressed PR; 4% of ILCs and 13% of IDCs expressed c cerb B-2; ILCs and IDCs both expressed mib-1 in approximately 10% of lesional cells; 82% of ILCs and 54% of IDCs expressed cyclin D1; 90% of ILCs and 83% IDCs expressed p27 strongly; 4% of ILCs and 4% of IDCs expressed p53, 25% of ILCs and 33% of IDCs expressed mdm-2; 96% of ILCs and 100% of IDCs expressed bcl-2. None of the apparent differences were statistically significant. The ILC variants demonstrated immunophenotypes that were essentially similar to ILCs of the usual type. We conclude that ILCs and well-differentiated IDCs show similar proliferation and cell cycle control antigen profiles. Despite their unusual histologic features, most ILC variants appear to maintain a characteristic ILC immunophenotype.
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  • 43
    ISSN: 1573-7217
    Keywords: breast cancer ; in vivo tumor models ; Her-2/neu ; metastasis ; SCID mice ; soluble Her-2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract HER-2/neu is overexpressed on a variety of human adenocarcinomas and overexpression has been associated with a poor prognosis. For this reason, HER-2 has become an attractive target for immunotherapy. To facilitate testing of anti-HER-2-monoclonal antibodies (MAbs) and immunotoxins (ITs), we have evaluated the in vivo growth and metastatic spread of three HER-2-overexpressing human breast cancer cell lines (BT474, MDA-MB-453 and HCC1954) and one ovarian cancer cell line (SKOV3.ip1) in pre-irradiated male SCID mice using subcutaneous (s.c.), intravenous (i.v.) and intraperitoneal (i.p.) routes of injection. All the cell lines tested grew as s.c. tumors and the growth of BT474 and MDA-MB-453 cells after s.c. injection was improved by co-inoculation with Matrigel. Metastases to the lungs were detectable by PCR or histopathology after s.c. injection of BT474 and to a much lesser extent after s.c. injection of HCC1954, MD-MB-453 and SKOV3.ip1cells. I.P. injection of HCC1954 and SKOV3.ip1 cells produced fatal ascites while i.v. injection of SKOV3.ip1, but not BT474 or MDA-MB-453 cells, resulted in infiltration of lungs and death within 9–11 weeks.
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  • 44
    ISSN: 1573-7217
    Keywords: apoptosis ; breast cancer ; melatonin ; retinoic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It has been established that melatonin (Mlt) and retinoic acid, individually, inhibit the proliferation of the estrogen receptor-alpha (ERα)-positive MCF-7 breast cancer cell line. Our laboratory has previously demonstrated that Mlt and all-trans-retinoic acid (atRA) not only inhibit the proliferation, but also induce apoptosis of MCF-7 cells when used in a sequential regimen of Mlt followed 24 h later by atRA. Using this same MCF-7 breast cancer cell line, we investigated the potential pathways through which apoptosis is being induced. We found that treatment of MCF-7 cells with Mlt for 24 h before the addition of atRA decreased the protein levels of the death suppressor, Bcl-2, and increased, although with different time courses, the levels of the death promoters, Bax and Bak; however, there was no change in the levels of the tumor suppressor gene, p53. MCF-7 cells treated sequentially with Mlt and atRA also demonstrated an enhanced sensitivity to the apoptotic effects of atRA, which did not appear to be due to increased expression of the retinoic acid receptors, RARα or RXRα, but rather to enhanced transcriptional activity of the RARα. These data suggest that the sequential treatment regimen of Mlt and atRA may induce apoptosis by modulation of members of the Bcl-2 family of proteins. Thus, this combinatorial regimen, which reduces the concentration of atRA needed for clinical efficacy while enhancing its anti-tumorigenic activity, could be of great therapeutic benefit, and may, in fact, specifically induce the regression of established breast tumors due to its apoptosis-promoting effects.
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  • 45
    ISSN: 1573-7217
    Keywords: breast cancer ; 99m-Tc-tetrofosmin ; whole-body scintigraphy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose.To assess the value of 99m-Tc-tetrofosmin (tetrofosmin) scintigraphy in patients with palpable and non-palpable breast lesions. Patients and methods.Prospective, blinded trial. One hundred and fifty-nine consecutive patients with 163 breast lesions detected by clinical examination and mammography were included. Tetrofosmin scintigraphy of the breast was performed additionally to the regular diagnostic procedure. Using histologic assessment as the golden standard, sensitivity, specificity, positive and negative predictive value for tetrofosmin scintigraphy of the breast were assessed. Results.Overall sensitivity and specificity were 82% and 84%. The sensitivity for palpable tumors (65%) was 93% compared to 62% for non-palpable breast lesions. Malignant lesions were nearly twice as big as benign lesions (31.5 mm± 2.4 vs. 16.9 mm ± 2.4). Specificity, positive and negative predictive value (84%, 89%, and 66%) did not differ significantly in palpable versus non-palpable tumors. Of malignant tumors 18% were found false negative by tetrofosmin scintigraphy. Conclusion.The results suggest that tetrofosmin scintigraphy is a valuable tool for the evaluation of palpable breast cancer. In patients with non-palpable tumors, tetrofosmin scintigraphy may not add to the work-up of patients with breast cancer due to a low sensitivity rate.
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  • 46
    ISSN: 1573-7217
    Keywords: breast cancer ; comorbidity ; disability ; elderly ; formestane ; hormonal treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Age is a major risk factor for solid tumors, including breast cancer. The majority of elderly breast cancer patients have oestrogen-dependent tumors, thus, tamoxifen is widely administered. However, it has been noted that tamoxifen-related thrombotic events are not exceptional. Due to the increasing prevalence of comorbidity, including vascular diseases, with age, such events are more frequently observed in the aged patients. Formestane, a selective steroidal aromatase inhibitor, may represent a therapeutic option after failure with tamoxifen, or in the presence of vascular diseases contraindicating its administration. The present report provides a new clinical experience on a consecutive series of 45 elderly breast cancer women affected by moderate to severe degree of comorbidity and disability measured by a Comprehensive Geriatric Assessment (CGA) scale validated on oncological patients. Formestane was given intramuscularly at the dose of 250 mg every 2 weeks. The study included 31 patients who had metastatic disease, and 14 who received formestane as an adjuvant treatment. Median age was 74 years (range 65–93), with nine patients 〉 80 years. Median ECOG Performance Status (PS) was one. The more frequent comorbidities observed in our series were arthrosis-arthritis (64.4% of patients), hypertension (44.4%), vascular diseases (35.5%), CNS diseases (28.8%). Twenty percent of patients presented at least one dependency in Activities of Daily Living (ADL) and 51.2% in Instrumental Activities of Daily Living (IADL). The treatment was well tolerated – only two patients interrupted formestane because of minor adverse reaction at the injection site and generalised itching. In particular Formestane was not responsible for any worsening of pre-treatment comorbidities, especially hypertension and vascular diseases. Objective responses (OR) were observed in 11.1% of advanced patients, while the disease was stabilised in 51.8% subjects. Median duration of OR was 12 months; median overall survival was 11 months. Among patients receiving formestane as adjuvant treatment, three relapsed, with a time to failure (TTF) of 12 months. Formestane is effective and minimally toxic in an elderly breast cancer population with comorbidities and disabilities measured by CGA.
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  • 47
    ISSN: 1573-7217
    Keywords: breast cancer ; prognosis ; Nottingham histologic grade ; S-phase fraction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Flow cytometric DNA analysis with assessment of S-phase fraction and DNA ploidy was compared to Nottingham histologic grade. The study population consisted of 654 patients who presented between 1987 and 1996 with primary operable breast cancer and whose tumours had been analysed for S-phase fraction and DNA ploidy at the time of surgery. Grade, tumour size, node status, steroid receptor status, age, S-phase fraction and DNA ploidy were analysed univariately and multi-variately in a Cox proportional hazard analysis. In the univariate analyses all parameters were statistically significantly associated with breast cancer mortality during the follow-up period of 2–11 years. The most powerful predictor of death from breast cancer in the multiple regression analysis was grade. Patients with grade 1 tumours have excellent prognosis. We conclude that tumour grade is a strong prognostic indicator applicable to all breast cancer patients, regardless of size and nodal status, and advocate its general use.
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  • 48
    ISSN: 1573-7217
    Keywords: breast cancer ; c-erbB-2 ; early onset ; HER-2/neu ; immunohistochemistry ; prognostic factors ; young age
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Young breast cancer patients have a decreased survival rate and it has been demonstrated that young age is an independent predictor of adverse prognosis. Overexpression of c-erbB-2 protein (also known as HER-2/neu) has been shown to be a prognostic indicator in breast cancer in general and especially among patients with axillary nodal metastases. The present study was initiated to determine the prognostic significance of c-erbB-2 protein overexpression in early onset breast cancer. A population consisting of 110 young breast cancer patients, ≤ 36-year-old at diagnosis, was analyzed with immunohistochemical staining for c-erbB-2 protein. Thirty patients (27%) were found to overexpress the c-erbB-2 protein. C-erbB-2 positivity was significantly associated with poor survival when all patients were included in the analysis (P = 0.002) and for patients with axillary nodal metastases (P = 0.0007). No such association was found for node-negative patients. Furthermore, the difference in prognosis in relation to c-erbB-2 among node-positive patients was maintained, when these were stratified in groups treated or not treated with adjuvant chemotherapy. The study indicates that overexpression of c-erbB-2 protein is a strong prognostic factor in young breast cancer patients with axillary nodal metastases. Moreover, the adverse prognosis associated with c-erbB-2 overexpression in node-positive patients was observed whether or not the patients had received adjuvant chemotherapy.
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  • 49
    ISSN: 1573-7217
    Keywords: alpha fetoprotein ; breast cancer ; estradiol ; estrogen receptor ; peptides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Alpha-fetoprotein (AFP) is a transporter of various serum ligands and regulator of cellular growth during pregnancy. Estrogens modify AFP to exhibit growth suppressive properties. We recently synthesized a peptide (P149) from human AFP that suppresses the growth of mouse uterus and MCF-7 breast cancer cells. Here it is shown that molar excess treatment of native AFP with estradiol-17β (E2) exposes the P149 site on AFP. The anti-estrogenic and anti-tumor activities of AFP-peptides were tested in vivo in the immature mouse uterine assay and mammary tumor (6WI-101)-induced ascites assay, and in vitro in a cytostatic assay using five different human breast tumor cell lines. AFP-peptide P149, and fragments of P149, P149A and P149C but not P149B, suppressed the growth in both in vivo assays. P149 also suppressed the in vitro growth of MCF-7, MDA-MB-231, MDA-MB435 breast cancer cells by more than 75%. P149 and P149A bound the estrogen receptor-α (ER) with low affinities compared to E2 and tamoxifen, while P149B bound 3H-E2 with 105 fold less affinity compared to ER. The recent epidemiologic observation that high AFP levels in young pregnant women reduce their subsequent risk of postmenopausal breast cancer may be related to the growth suppressive property of AFP with the exposed P149 epitope.
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  • 50
    ISSN: 1573-7217
    Keywords: breast cancer ; heterogeneity ; lymph nodes ; ploidy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Human breast carcinoma is biologically heterogeneous, and its clinical course may vary from one which is indolent to one which rapidly progresses. Although it is the metastasis rather than the primary tumor that ultimately overwhelms the patients, studies concerning the DNA pattern have focused on the primary tumors. This study was undertaken to identify heterogeneities between primary tumors and metastases, and to evaluate the prognostic significance of the ploidy pattern and the S-phase fraction (SPF) of metastatic nodes in axillary node positive patients. Seventy-four frozen specimens of the primary and corresponding metastatic nodes from 37 patients have been analyzed by flow cytometry and the SPF calculated. The results of ploidy pattern analysis in primaries revealed 25 diploidy (67.6%) and 12 aneuploidy (32.4%), while those in metastasis showed 17 diploidy (46.0%) and 20 aneuploidy (54.0%). The aneuploidy group in metastatic nodes had the poorer histological grade (85.0% vs. 15.0%, p = 0.02), and more mean metastatic nodes (5.75 ± 2.10 vs. 3.05 ± 1.56, p = 0.018), and more frequent lymphatic vessel invasion (65.0% vs. 11.8%, p = 0.031) than its counterpart. Decreased expression of ER (70.6% vs. 25.0% p = 0.006) and increased expression of c-erbB2 (65.0% vs. 23.5%, p = 0.012) were observed in the aneuploidy of metastatic nodes. The group with higher SPF in metastatic nodes had more metastatic nodes (5.47 ± 2.31 vs. 4.00 ± 1.78, p = 0.042), and the higher incidence of lymphatic vessel invasion (57.9% vs. 22.2%, p = 0.027), and poor histological grade (71.4% vs. 37.5%, p = 0.039). In conclusion, the cell populations in metastatic nodes revealed DNA pattern which differed from that of primary tumors. The ploidy pattern and SPF in metastatic nodes might be considered as discriminate measure for risk factors in breast cancer patients with positive axillary node.
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  • 51
    ISSN: 1573-7217
    Keywords: adjuvant chemotherapy ; breast cancer ; decision-making ; treatment preference ; decision board instrument
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose.To examine the effects of framing of outcome and probabilities of cancer occurrence on the treatment preference which breast cancer patients indicate for hypothetical patient scenarios. Methods.A modified version of the Decision Board Instrument (Levine et al. 1992) was administered to 35 breast cancer patients with past ACT experience. Patients expressed their choice regarding ACT for six scenarios which were characterized by either negative or positive framing of outcome and by one of the three levels of probability of recurrence (high, medium, low). Results.The framing had no influence on ACT choices over all three probability levels. The majority chose ACT for high and medium risk and one third switched from ACT to No ACT in the low-risk condition. This switch was statistically significant. Conclusion.Hypothetical treatment decisions against ACT occur only when the probability of recurrence is low and the benefit of ACT is small. This finding for patients with past experience of ACT is similar to those reported for other oncological patient groups still in treatment.
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  • 52
    ISSN: 1573-7217
    Keywords: nipple discharge ; breast cancer ; diagnosis ; loss of heterozygosity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Nipple discharge in breast cancer cases was examined loss of heterozygosity (LOH). DNA samples were extracted from both supernatant and cell pellet components of the discharge, and examined for LOH at microsatellite markers, D11S1818, D11S2000, D16S402, D16S504, D16S518, D17S520, and D17S786. At least one LOH was found in either the supernatant or cell pellet in seven out of 10 patients (70%). Five of seven samples, which were cytologically negative, were LOH positive, and only one case, which was cytologically positive, showed no LOH on the markers examined. All three samples, which were judged ‘negative’ by CEA measurement (〈400 ng/ml), were LOH positive. This method could be a useful novel diagnostic modality for nonpalpable breast cancer with nipple discharge.
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  • 53
    ISSN: 1573-7217
    Keywords: breast cancer ; carcinoma extension ; ductal carcinoma in situ ; histological mapping ; 3D MRI
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study was initiated to clarify the ability of magnetic resonance imaging (MRI) in defining breast carcinoma extension by comparing MRI to detailed histopathological analysis. Mastectomy (n=14) or quadrantectomy (n=44) specimens were sub-serially sectioned and mapped in detail in 58 breast cancer patients. Morphologically, we classified the lesions utilizing MRI into three patterns in relation to their histology. Numerically, we assessed the maximum distance of carcinoma extension using MRI, mammography, and ultrasonography (US). Linear regression was calculated for each of the three imaging measurements versus histopathological measurements. Three imaging patterns were observed by MRI, (1) localized (n=30), (2) segmentally extended (n=19), and (3) irregularly extended (n=5). The localized pattern showed a distinct focal mass, but in 10 cases, microscopic ductal carcinoma in situ (DCIS), or invasive lobular carcinoma, which were not depicted by MRI, existed. The segmentally extended pattern showed diffuse enhancement along duct–lobular segments, forming a ‘cone’ shape. Histologically, pure (n=4) or predominant (n=10) DCIS was distributed segmentally. The irregularly extended pattern showed thick branches extending out from the index tumor which were histologically revealed to be stromal invasion of ductal carcinoma. From the results of linear regressions, MRI was the most accurate modality in histologically measuring the extent of the cancer. When cases were limited to patients who were classified into segmentally or irregularly extended pattern by MRI (n=24), MRI was more accurate than mammography and US, even if they were combined (P〈0.05). MRI may provide additional information concerning carcinoma extension prior to surgery, especially in patients classified into ‘extended patterns’ by MRI.
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  • 54
    ISSN: 1573-7217
    Keywords: breast cancer ; growth hormone-releasing hormone (GH-RH) antagonists ; IGF-I ; IGF-I receptor ; GH-RH
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Since antagonists of growth hormone-releasing hormone (GH-RH) inhibit proliferation of various tumors, in this study we investigated the effects of GH-RH antagonists MZ-5-156 or JV-1-36 on growth of estrogen-independent MDA-MB-468 human breast cancers xenografted into nude mice. Both GH-RH antagonists administered at a dose of 20 μg/day induced regression of some and growth-arrest of other tumors, while control tumors continued to grow. After 5 weeks of therapy with MZ-5-156 or JV-1-36, final volume and weight of MDA-MB-468 tumors were significantly decreased (all p values 〈0.001) and serum IGF-I levels as well as tumor IGF-I mRNA expression were reduced as compared with controls. High affinity binding sites for IGF-I were detected by the ligand binding method. Gene expression of human IGF-I receptors, as measured by the RT-PCR, was not significantly different in control and treated MDA-MB-468 tumors. In cell culture, IGF-I did not stimulate, GH-RH slightly stimulated, while MZ-5-156 and JV-1-36 inhibited proliferation of MDA-MB-468 cells known to possess defective insulin and IGF-I receptor signaling. The expression of mRNA for human GH-RH was found in five of 8 tumors treated with GH-RH antagonists, and in one of the five control tumors. These results suggest that GH-RH antagonists inhibit MDA-MB-468 breast cancers possibly through mechanisms involving interference with locally produced GH-RH.
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  • 55
    ISSN: 1573-7217
    Keywords: axillary dissection ; breast cancer ; morbidity ; quality of life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective. This study describes in detail the surgery-related symptoms following axillary lymph node dissection in breast cancer patients and considers both their significance for long term quality of life and the impact of possible influencing factors. Material and methods: Three hundred and ninety six patients were studied retrospectively using a self-report questionnaire and a clinical examination. The symptoms, numbness, pain, edema, arm strength and mobility were evaluated. The subjective assessment of the degree of symptom intensity was compared with objective measurements. The extent of surgery (number of resected nodes, level of dissection) as well as the influence of demographic, oncologic and adjuvant measures (age, time interval, number of involved nodes, chemotherapy) were evaluated. Results. Shoulder-arm morbidity and fear of cancer recurrence were the most important long-term sources of distress following breast cancer surgery in our study population. Demographic, oncologic and therapeutic measures including the extent of surgery had no influence on long-term morbidity. The intensity of all evaluated symptoms was reported to be more severe in patients' subjective statements than in the results of clinical assessment. Conclusion. Shoulder-arm morbidity following axillary dissection is a frustrating polysymptomatic disease that seems to be relatively unaffected by therapeutic measures. The surgical trauma necessary for adequate tumor staging (removal of 10 lymph nodes) seems decisive for the postsurgery syndrome following axillary dissection. For node-positive patients complete axillary clearing may improve tumor control without worsening long-term-morbidity. New techniques, such as the sentinel-node-biopsy, that selects patients with negative axillary status while preserving the integrity of axillary structures, may improve the overall morbidity.
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  • 56
    ISSN: 1573-7225
    Keywords: alcohol ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objectives: To study the association between alcohol consumption and breast cancer risk. Methods: A case–cohort analysis was undertaken within the cohort of 56,837 women who were enrolled in the Canadian National Breast Screening Study (NBSS) and who completed a self-administered dietary questionnaire. (The NBSS is a randomized controlled trial of screening for breast cancer in women aged 40–59 at recruitment.) The cohort was recruited between 1980 and 1985, and during follow-up to the end of 1993 a total of 1469 women in the dietary cohort were diagnosed with biopsy-confirmed incident breast cancer. For comparative purposes a subcohort consisting of a random sample of 5681 women was selected from the full dietary cohort. After exclusions for various reasons the analyses were based on 1336 cases and 5238 noncases. Results: When compared to nondrinkers the adjusted incidence rate ratios (95% confidence intervals) for those consuming 〉 0 and  ≤ 10 g of alcohol/day,  〉 10 and  ≤ 20 g/day,  〉 20 and  ≤thinsp;30 g/day,  〉 30 and  ≤ 40 g/day,  〉 40 and  ≤ 50 g/day, and  〉 50 g/day were 1.01 (0.84–1.22), 1.16 (0.91–1.47), 1.27 (0.91–1.78), 0.77 (0.51–1.16), 1.00 (0.57–1.75), and 1.70 (0.97–2.98), respectively; the associated p value for the test for trend was 0.351. Similar findings were obtained when analyses were conducted separately in the screened and control arms of the NBSS, in premenopausal and postmenopausal women, for screen-detected and interval-detected breast cancer, and by levels of other breast cancer risk factors. Conclusions: The results of this study suggest that alcohol consumption might be associated with increased risk of breast cancer at relatively high levels of intake.
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  • 57