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Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seven patients with metastatic breast cancer presenting as gastrointestinal primary are described. These included six gastric and one colonic lesions. None of the patients had known systemic metastases at the time of diagnosis. The mean age at presentation was 66.7 yr (range 55-78). Median interval between breast cancer and gastrointestinal metastasis diagnosis was 6 yr (range 0.25-12.5). Original breast cancer histology included infiltrating lobular cancer (n = 4), infiltrating ductal cancer (n = 1), and a mixed type (n = 2). All patients with gastric involvement presented with epigastric pain and early satiety; the patient with colonic involvement had heme-positive stool. In three cases of gastric tumor and the one case of colonic tumor presentation, a definitive diagnosis of metastatic breast cancer was only confirmed after surgical resection of a presumed primary gastric or colonic malignancy. In the other three cases, pathological diagnostic confirmation was obtained through endoscopic biopsies and comparison to breast biopsy material, and operative treatment was avoided in favor of systemic cytotoxic therapy. The diagnosis was confirmed through similarities between mammary and gastric histopathology with regard to growth pattern, hormone receptor status, or gross cystic disease fluid protein. A high level of suspicion for metastatic breast cancer and a detailed pathological analysis will help avoid unnecessary surgical treatment in patients with a history of mammary carcinoma presenting with a newly diagnosed gastrointestinal neoplasm.
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PMID:Metastatic breast cancer masquerading as gastrointestinal primary. 944 88

IIB-BR-G is an undifferentiated, highly heterogeneous, hormone receptor negative human breast cancer cell line previously established in our laboratory from a patient's primary tumor. An in vitro growing cell line (IIB-BR-G) and a xenotransplanted tumor growing in nude mice (IIB-BR-G(NUDE)) were derived. To further characterize these systems, immunocytochemical analysis was performed for differentiation antigens (PEM 200 kDa, CEA, NCA 90 kDa), blood-group related antigens (Le(x), sTn), oncogenes and tumor suppressor gene products (Her-2/neu protein, p53), metastasis-related cathepsin D and CD63/5.01 Ag, and the chemokine monocyte chemotactic protein 1 (MCP-1). Expression of markers was heterogeneous in these different systems. Previously reported karyotypic analysis has shown extensive chromosomal alterations including double min. Searching for oncogene amplification, we detected augmented copy number of c-myc and c-fos, the last one with two rearranged fragments. No amplification was found for c-erbB-2 in the cell line or in IIB-BR-G(NUDE), although this oncogene was amplified in the patient's primary tumor DNA. The differences observed between the patient's tumor, the cell line and the IIB-BR-G(NUDE) tumors are probably due to clonal expansion of cell variants not present in the original tumor. Electron microscopy of IIB-BR-G growing cells revealed epithelial characteristics with abundant dense granules, presumably secretory, distributed all over the cytoplasm and great nuclear pleomorphism. In vitro, IIB-BR-G cells showed a significant number of invading cells by Matrigel assay. After nearly 40 sequential subcutaneous passages of the original xenograft through nude mice, 80% of recipients developed spontaneous metastases, primarily to the lung and lymph nodes. Since this experimental model allowed to analyze changes produced in cancer cells from the primary tumor during adaptation to in vitro and in vivo growth, our results provide novel insights on the behaviour of hormone independent metastatic breast cancer.
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PMID:The human breast cancer cell line IIB-BR-G has amplified c-myc and c-fos oncogenes in vitro and is spontaneously metastatic in vivo. 962 Apr 46

Most clinical trials using dose-intensive chemotherapy exclude patients with brain metastases. This exclusion was based on anecdotal experience reflecting high treatment-related mortality. We analyzed the outcome of 11 patients with metastatic breast cancer who had brain metastases, diagnosed either before or during high-dose chemotherapy. In three patients, the death was attributed to non-central nervous system (CNS) regimen-related toxicity. Five patients died as a results of non-CNS disease progression. One patient died as a result of both CNS and non-CNS disease progression. Two patients are alive without disease progression with follow-up of 13.4 and 7.3 months, respectively. Of the five patients who have survived 1 year, four have hormone receptor expression and continued on antihormone therapy after high-dose therapy. These results are the first to show that breast cancer patients having brain metastases who receive high-dose chemotherapy do not experience more treatment-related complications or treatment failure as a result of the metastatic CNS disease. To this end, exclusion of these patients from high-dose therapy trials, especially those with expression of hormone receptors, needs to be reevaluated.
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PMID:Dose-intensive chemotherapy for breast cancer with brain metastases: a case series. 1044 Jan 92

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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PMID:Metastatic breast cancer: clinical course, prognosis and therapy related to the first site of metastasis. 1083 97

This report summarizes information on drugs recently approved by the Food and Drug Administration, Office of Drug Evaluation I, Division of Oncology Drug Products. Five applications supporting new claims will be discussed: Trisenox (arsenic trioxide) for induction of remission and consolidation in patients with acute promyelocytic leukemia who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose disease is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression; Nolvadex (tamoxifen citrate) in women with ductal carcinoma in situ, following breast surgery and radiation, to reduce the risk of invasive breast cancer; Arimidex (anastrazole) for first-line treatment of postmenopausal women with hormone receptor positive or hormone receptor unknown locally advanced or metastatic breast cancer; Taxol (paclitaxel), 175 mg/m(2) by 3 h infusion in combination with cisplatin for first-line treatment of advanced ovarian cancer; and Targretin gel (bexarotene) for the topical treatment of cutaneous lesions in patients with stage IA and IB cutaneous T-cell lymphoma who have not tolerated other therapies or who have refractory or persistent disease. Information provided includes rationale for drug development, study design, efficacy and safety results, and pertinent literature references.
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PMID:Drug approval summaries: arsenic trioxide, tamoxifen citrate, anastrazole, paclitaxel, bexarotene. 1116 Dec 23

Eighty-eight women presenting with locally advanced or metastatic breast cancer were treated with tamoxifen alone. Estrogen and progesterone receptors (ER and PR) were immunocytochemically analysed in mammary tumour cells obtained by fine needle sampling from 73 patients. Of the breast carcinomas, 34.2% were ER+/PR+ and 43.8% were ER-/PR-. The ER+ content increased with age in postmenopausal women. After tamoxifen treatment objective remission occurred in 39.7% of the women. The overall response rate was 53.3% in the ER+/PR- group and 73.1% in the ER+/PR+ group. However, the response elicited in a case of the ER-/PR- phenotype justified the randomized use of tamoxifen among patients in Iraq where the necessary requirements for hormone receptor assessment are almost unavailable.
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PMID:Assessment of response to tamoxifen among Iraqi patients with advanced breast cancer. 1155 39

A 42-year-old woman, who had received right breast-conserving therapy 5 years previously, was admitted with hemoptysis. Chest X-rays showed a tumor shadow in the left pulmonary hilus with partial atelectasis in the left lower lobe. Bronchofiberscopic examination showed a polypoid tumor arising from the endobronchial wall, with bleeding and a white surface coat. Although, microscopically, the tumor resembled the breast cancer resected previously, as we could not rule out primary lung carcinoma, and as the tumor seemed to be localized, thoracotomy was performed. During posterolateral thoracotomy, however, pleural metastatic nodules were found; therefore, only sampling of these nodules and the administration of 50 mg of cisplatin (CDDP) into the thoracic cavity were performed. From a comparison of the histopathological features of the original tumor and the intrathoracic tumor, and from the hormone receptor positivity of the pleural metastasis, we diagnosed the intrathoracic tumor as being highly suspicious of metastasis from breast cancer. The measurement of hormone receptor was informative for the diagnosis of and for selecting a therapeutic strategy for the metastatic breast cancer.
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PMID:Endobronchial metastasis of breast cancer 5 years after breast-conserving therapy. 1170 49

We report on the prognostic significance of tumorbiologic parameters and CD34(+) cell dose in 120 patients with metastatic breast cancer (MBC) who received high-dose chemotherapy (HDCT) with autologous blood stem cell transplantation as first-line treatment. Her2/neu, p53, Ki67, and bcl-2 protein expression were studied using immunohistochemical staining on formalin-fixed, paraffin-embedded primary tumor sections. DNA content of tumor cells (DNA-index) and tumor cell proliferation (S-phase fraction) were measured by DNA flow cytometry. The relationship between these parameters and the CD34(+) cell dose and progression free (PFS) and overall survival (OS) was analyzed. With a median follow-up period of 40 months (range, 7-89 months), no more than two metastatic sites (relative risk [RR] = 3.84 [95% confidence interval (CI) 1.49-10]; p =.005) and hyperploidy (RR = 2.58 [95% CI 1.26-5.26]; p =.009) were independent predictors of longer PFS according to multivariate analysis. Independent prognostic factors of longer OS included one or two metastatic sites (RR = 4.16 [95% CI 1.96-4.16]; p <.001), a positive combined hormone receptor status (RR = 2.45 [95% CI 1.45-4.14]; p =.001) and a high number of infused stem cells (>7.8 x 10(6) CD34(+) cells per kg body weight) (RR = 2.0 [95% CI 1.17-3.42]; p =.01). In conclusion, positive hormone receptors, < or =2 metastatic sites, high DNA-index and high CD34(+) cell dose (>7.8 x 10(6) CD34(+) cells per kg) are predictors for a favorable outcome after autotransplantation for MBC. Our observation might indicate a favorable effect of HDCT in MBC patients with overexpression of Her2/neu who might have a worse prognosis when treated with conventional chemotherapy.
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PMID:Stem cell dose and tumorbiologic parameters as prognostic markers for patients with metastatic breast cancer undergoing high-dose chemotherapy with autologous blood stem cell support. 1179 20

We conducted a single-institution study to determine whether local therapy plus six cycles of chemotherapy with 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) followed by 5 years of tamoxifen is superior to local treatment alone in terms of disease-free survival (DFS) and overall survival (OS) in patients with stage IV breast cancer with no evidence of disease (stage IV-NED breast cancer). Patients with breast cancer were eligible if they had histologic proof of a locoregional or distant recurrence that had been curatively resected, irradiated, or both and had no other evidence of disease. Patients who had received prior anthracycline therapy were not eligible. All patients received six cycles of intravenous FAC, with cycles repeated every 3 weeks. After completion of chemotherapy, patients whose tumors had not previously demonstrated resistance to tamoxifen and had positive or unknown estrogen receptor status received tamoxifen 20 mg by mouth daily for 5 years. Patients in this study were compared with a historical control population (patients with stage IV-NED breast cancer who never received systemic therapy) as well as with the patients in two previously reported trials of chemotherapy for stage IV-NED disease. Forty-seven patients were registered, but only 45 were evaluable. There was a highly statistically significant difference ( p < 0.001) in OS and DFS among the four groups, with patients in our most recent study having the best OS and DFS at 3 years compared with the control group (84% vs. 55% and 66% vs. 11%, respectively). When patients in all four groups were analyzed together in search of prognostic factors, we found that patients whose primary tumors had negative axillary lymph nodes had a statistically significant improvement in OS and DFS ( p < 0.01) compared with patients with positive axillary lymph nodes. No survival differences were found between patients with positive and those with negative hormone receptor status. This study demonstrates a benefit in terms of OS and DFS for patients with stage IV-NED breast cancer who receive doxorubicin-based adjuvant chemotherapy. The benefit was greater on patients with node-negative primary tumors. In patients with stage IV-NED disease, doxorubicin-based chemotherapy should be considered standard treatment after adequate local control is achieved.
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PMID:Fluorouracil, doxorubicin, and cyclophosphamide followed by tamoxifen as adjuvant treatment for patients with stage IV breast cancer with no evidence of disease. 1185 54

Letrozole (Femara; Novartis Pharmaceuticals Corp., East Hanover, NJ) is a nonsteroidal inhibitor of aromatase enzyme complex. It inhibits the peripheral conversion of circulating androgens to estrogens. In postmenopausal women, letrozole decreases plasma concentrations of estradiol, estrone, and estrone sulfate by 75-95% from baseline with maximal suppression achieved within 2-3 days of treatment initiation. Suppression is dose related, with doses of >or=0.5 mg giving estrone and estrone sulfate values that were often below assay detection limits. At clinically used dosage, letrozole does not impair adrenal synthesis of glucocorticoids or aldosterone. In 1998, letrozole was approved by the United States Food and Drug Administration (FDA) for the treatment of advanced breast cancer in postmenopausal women, with hormone receptor positive or unknown breast cancer, who had failed one prior antiestrogen treatment (i.e., for "second-line" treatment). Approval was based on two randomized trials comparing tumor RRs of patients receiving 0.5 mg of letrozole, 2.5 mg of letrozole, and either megestrol acetate (MA) or aminoglutethimide. In the megestrol trial, 2.5 mg/day letrozole was superior to 0.5 mg of letrozole and MA (RRs 24, 13, and 16%, respectively), whereas in the aminoglutethimide trial, there was no significant difference in 2.5 mg of letrozole and 0.5 mg of letrozole RRs (20 and 17%). There was a trend toward RR superiority of 2.5 mg of letrozole over aminoglutethimide (P = 0.06). Letrozole (2.5 mg) was the dose chosen for comparison with tamoxifen in the first-line setting. In July 2000, a marketing application for first-line letrozole treatment of postmenopausal women with hormone receptor positive or hormone receptor unknown locally advanced or metastatic breast cancer was submitted to the FDA. A single double-blind, double dummy, randomized, and multicenter trial compared 2.5 mg of letrozole to 20 mg of tamoxifen (456 patients/arm). Letrozole was superior to tamoxifen with regard to time to progression (TTP) and objective response rate (RR). The median TTP for letrozole treatment was 9.9 months [95% confidence interval (CI) 9.1-12.2] versus 6.2 months (95% CI 5.8-8.5) for tamoxifen, P = 0.0001, hazard ratio 0.713, (95% CI 0.61-0.84). RR was 32% for letrozole versus 21% for tamoxifen (odds ratio 1.74, 95% CI 1.29-2.34, P = 0.0003). Preliminary survival data (survival data are still blinded) indicate that letrozole is unlikely to be worse than tamoxifen. Both treatments were similarly tolerated. On the basis of these results, the United States FDA approved letrozole tablets, 2.5 mg/day, for first-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor-unknown locally advanced or metastatic breast cancer. The manufacturer made a commitment to provide updated information on survival.
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PMID:Approval summary: letrozole in the treatment of postmenopausal women with advanced breast cancer. 1189 93


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