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

Sequential administration of endocrine therapies can result in objective remission in a significant fraction of patients with metastatic breast cancer. Combined hormonal therapies and combined hormonochemotherapies have not resulted in better results than the sequential administration of these same therapies. Tamoxifen (an antiestrogen) given as an initial therapy results in local control of the disease in a significant fraction of patients with locally advanced breast cancer who are not candidates for cytotoxic therapy. Tamoxifen as an adjuvant therapy for operable breast cancer prolongs disease-free survival and reduces mortality in patients greater than 50 yr of age with higher estrogen receptor concentrations. The role of tamoxifen as adjuvant therapy for patients less than 50 yr of age remains unclear. Also, adjuvant tamoxifen in combination with cytotoxic drugs has not produced superior results, and the duration of adjuvant tamoxifen therapy remains to be determined. Experimental data suggest prolonged administration of tamoxifen may be needed to control micrometastases.
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PMID:Current status of endocrine treatment of carcinoma of the breast. 218 45

In premenopausal women with metastatic breast cancer, differences in survival curves early during follow-up can be misleading. The authors therefore analyzed long-term survival in 378 patients, entered in three randomized trials, started between 1973 and 1978. Combined data from the three trials were used to increase the power for identifying prognostic variables. Cancer and Leukemia Group B (CALGB) trial 7382 randomized patients to oophorectomy plus either cyclophosphamide or combination chemotherapy or observation. Eastern Cooperative Oncology Group (ECOG) 2174 randomized patients who had not progressed 3 months after oophorectomy to combination chemotherapy or combination chemotherapy or observation. Trial ECOG 2177 randomized estrogen receptor (ER) positive or ER-unknown patients to oophorectomy plus combination chemotherapy or immediate combination chemotherapy, and ER-negative patients were directly assigned to combination chemotherapy. Hence ER-negative patients need not have been healthy enough to be randomized to oophorectomy. With only 14% of the patients still alive, median survival on the three studies was 30, 24, and 28 months. The median survival of individual treatments changed noticeably in ECOG 2174 and ECOG 2177 with long-term follow-up. At this time there are no differences in survival between randomized regimens in any of the three trials. In a multivariate model, factors associated with significantly poorer survival were visceral-dominant disease, nodal metastases, breast metastases, age younger than 45 years, ER negativity, and not receiving chemotherapy immediately after oophorectomy. This treatment difference was thus not due to imbalances in the prognostic variables used in the model, but it may be due to imbalances of unknown prognostic factors or differences in patient selection.
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PMID:Survival of premenopausal women with metastatic breast cancer. Long-term follow-up of Eastern Cooperative Group and Cancer and Leukemia Group B studies. 220 13

Spontaneous and lipopolysaccharide (LPS)-induced production of tumor necrosis factor (TNF) by peripheral blood macrophages was investigated in breast cancer. Whereas spontaneous TNF production by macrophages derived from patients with breast cancer was comparable with the one found in healthy controls (P greater than 0.1), LPS-stimulated macrophages derived from patients in the disease-free interval as well as with metastatic breast cancer were found to produce significantly lower amounts of TNF, as compared with macrophages derived from healthy control individuals (P less than 0.0005). However, the production of TNF did not significantly differ between the two patient populations (P greater than 0.05). The impairment of LPS-induced TNF production did not depend upon such characteristics of the primary tumor as size, axillary lymph node and estrogen receptor status, or upon the fact of administration of adjuvant chemotherapy and, in patients with metastatic disease, hormone treatment. To further investigate cytokine production by macrophages, spontaneous and LPS-induced interleukin-1 (IL-1) production was investigated also. However, no difference was found between patients and controls concerning IL-1 generation. The authors thus conclude that LPS-induced TNF production was impaired in breast cancer independent of the presence of detectable metastatic disease, whereas IL-1 production remained unimpaired.
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PMID:Impaired production of tumor necrosis factor in breast cancer. 222 91

Fifty-one patients with metastatic breast cancer were investigated to determine tumor parameters with prognostic significance. Investigations included determinations of P24 content by immunocytochemical means using a monoclonal antibody to P24 protein; immunocytochemical analysis of estrogen and progesterone receptors; ploidy analysis by flow cytometry, and histologic grading. There were significant correlations between the presence of P24 and estrogen receptor, between histologic grade and P24 expression, and between estrogen and progesterone receptors. Of the tumor factors investigated only P24 protein was, however, of prognostic significance. Patients with P24-positive tumors had a significantly higher rate of response to treatment as well as more prolonged duration of response and duration of survival from diagnosis of metastatic disease. None of the other variables investigated were significantly predictive of outcome. P24 protein may be a useful predictor of prognosis in metastatic breast cancer.
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PMID:Tumor factors predicting for prognosis in metastatic breast cancer. The presence of P24 predicts for response to treatment and duration of survival. 224 95

Although patients with advanced breast cancer usually die of their disease, the clinical course is highly variable. Numerous investigators have examined potential prognostic factors predicting time to recurrence for primary (localized) breast cancer. Less attention has been paid to evaluating prognostic factors in patients presenting with metastatic disease. A group of 86 women with metastatic breast cancer diagnosed between 1974 and 1984 was studied to determine the effect of certain prognostic factors on survival. Univariate analysis of these factors indicates that specific sites of recurrence, estrogen receptor (ER) status, size of the primary tumor at original diagnosis, and tumor histology; i.e., tumor differentiation, were significantly associated with predicting survival in patients presenting with metastatic disease. Poor survival, i.e., less than, or equal to, 22 months from initial presentation, is associated with a primary tumor greater than five cm., ER level less than 10 fmol/mg. of protein, lung and bone marrow recurrence, and poorly differentiated histology. Menstrual status, age, bone or lymph node site of metastases, and elapsed time between patient knowledge of symptoms and subsequent initial medical evaluation were not significant predictors of survival in patients presenting with metastatic disease.
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PMID:Prognostic factors determining survival in breast cancer patients presenting with metastatic disease. 230 Nov 63

Trilostane, which causes a perturbation of adrenal steroidogenesis, was studied in combination with hydrocortisone in 32 women with progressive metastatic breast cancer. Trilostane was administered orally at a dosage level of 240 mg four times daily after escalation over the first 10 days from 60 mg four times daily. Hydrocortisone was given orally at doses of 10 mg at 8 a.m. and 5 p.m. and 20 mg at bedtime. Patients must have been postmenopausal (81%) or previously castrated (19%), had a response to the hormonal treatment just prior to study (81%) or a positive estrogen receptor at time of entry on study (41%), and a measurable indicator lesion. The number of prior hormonal therapies was 1 in 19 patients (59%), 2 in 12 patients (38%), and 3 in 1 patient (3%), respectively. Twelve patients (38%) achieved an objective response, and a 95% confidence interval for this result is from 21 to 56%. The median time to disease progression was 140 days, median duration of response was 278 days, and median survival was 556 days. Common toxicities included lethargy, lightheadedness, diarrhea, and abdominal discomfort. Eleven patients required a dosage reduction, usually because of gastrointestinal side effects, and one additional patient had the trilostane discontinued because of leukopenia. We conclude that the combination of trilostane plus hydrocortisone appears to have definite antitumor activity in women with metastatic breast cancer who have characteristics favorable for response to hormonal therapy.
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PMID:Evaluation of trilostane plus hydrocortisone in women with metastatic breast cancer and prior hormonal therapy exposure. 231 87

We have used high-dose therapy followed by randomization to receive or not receive autologous bone marrow infusion in 58 stage IV breast cancer patients (all were estrogen receptor-negative [ER-] or primary hormonal refractory). Patients received a median of four courses of induction chemotherapy and if stable or responding received two courses of intensive therapy with cyclophosphamide 4.5 to 5.25 g/m2, etoposide 750 to 1,200 mg/m2, and cisplatin 120 to 180 mg/m2 (CVP). The complete remission (CR) rate after completion of the induction and intensive phases was 55%. Median progression-free interval from induction is 57 weeks with a projected 2-year progression-free survival of approximately 25%. Six of seven patients followed for greater than 2 years are still progression-free. Three favorable features predicted for improved progression-free survival are the following: (1) absent liver involvement, (2) absent soft tissue involvement, and (3) less than or equal to two disease sites (P values of .001, .013, and .048, respectively). Hormonal and menopausal status did not predict for progression-free survival. Major toxicities were infectious secondary to neutropenia, with a 93% incidence of fever and a 38% incidence of sepsis. The treatment-related mortality rate was 9%, with three infectious, one coronary, and one late hemorrhage-related death of unknown cause. Longer follow-up is still needed to truly evaluate the possibility of long-term disease-free survival, but further studies of this approach to high-dose intensification in poor prognostic groups of stage IV breast cancer appear warranted.
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PMID:Treatment of estrogen receptor-negative or hormonally refractory breast cancer with double high-dose chemotherapy intensification and bone marrow support. 235 37

Aminoglutethimide (AG) was administered as palliative therapy in 112 patients with metastatic breast cancer. In 36 patients, the dose level was 1000 mg/day; 76 patients received a dose level of 500 mg/day. Patients with brain or liver metastasis were excluded, as were patients with tumors determined to be negative for estrogen receptors. Objective regression was observed in 35 (31%) patients, with the duration of response ranging from 4 to 36 + months (mean, 12 months; median, 10 months). Response was observed in 11 of 31 (35%) patients with soft tissue metastasis; 16/59 (27%) patients with osseous metastasis; and 8 of 22 (36%) having visceral metastasis. In 93 patients with positive estrogen receptor (ER), 33 responded (35%), whereas in 19 patients with unknown ER status, two responded (11%). Response to previous treatment with tamoxifen (TAM) had occurred in 31 patients; of these, response to AG was noted in 11 (35%). Of 24 patients failing to respond to prior treatment with tamoxifen, four (17%) responded to subsequent therapy with AG. Thirteen patients had previously received combination chemotherapy, and response to AG was noted in two (15%). The side effects observed in this study included skin rash in ten patients, fever in eight, somnolence in three, weakness and dizziness in one, headache in one, insomnia in one, dyspnea in one, and ataxia in one. Treatment had to be discontinued in eight patients, due to the severity of the side effects. As expected, patients receiving AG at the lower dose level of 500 mg/day experienced fewer and less severe side effects than those treated with the higher dose. The response rate in the 1000 mg/day group was 10/36 (28%) and in the 500 mg/day group, it was 25/76 (33%). The lower dosage was better tolerated without apparent compromise in therapeutic efficacy.
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PMID:Aminoglutethimide in patients with metastatic breast cancer. 246 35

One hundred thirty-four pre- and perimenopausal patients presenting with metastatic breast cancer (median age, 42 years; range, 25 to 55) were treated with goserelin (Zoladex [ICI 118 630]; ICI Pharma, Plankstadt, Germany) a long-acting gonadotrophin-releasing hormone (GnRH)-analogue depot formulation, injected subcutaneously every 4 weeks, as a first-line therapy. One hundred eighteen patients were evaluable for response. Serum concentrations of estradiol, luteinizing hormones (LH), and follicle-stimulating hormones were significantly suppressed by Zoladex. Mean serum estradiol values fell into the range of castrated or postmenopausal women within 2 to 3 weeks of therapy. This suppression was maintained for the duration of therapy. Overall objective response was: 12 (10.2%) complete remission; 41 (34.7%) partial remission; 33 (28.0%) no change; and 32 (27.1%) progression. In responders, the median time to response was 4 months (range, 2 to 11 months), median duration of response was 8 + months (range 2 to 24 months), and median time to progression was 11 + months (range, 5 to 30 months). Objective responses were seen for different sites of metastases: loco-regional (62.5%), bone (46.7%), visceral (45.0%), and multiple (35.1%). Tumor remission was more common in patients in which the primary tumor was estrogen receptor (ER)-positive (49.3%) or ER-unknown (44.0%), but appreciable response rates were also observed in ER-poor patients (33.3%). Zoladex depot was well tolerated both locally and systemically. It produced effective castration and the objective response rates and duration of remission are at least comparable to those seen following oophorectomy; however, the side effects are less. The use of depot Zoladex avoids the psychological trauma and operative morbidity of the irreversible operative castration.
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PMID:Goserelin, a depot gonadotrophin-releasing hormone agonist in the treatment of premenopausal patients with metastatic breast cancer. German Zoladex Trial Group. 252 63

Thirty postmenopausal patients who had evaluable estrogen receptor-positive or unknown metastatic breast cancer were treated with cyclic sequential combined hormonal therapy consisting of 50 micrograms of ethinylestradiol orally daily for 7 days followed by 400 mg of medroxyprogesterone acetate orally daily for 21 days, followed in turn by 7 days of rest. Cyclic administration was continued until progressive disease was detected. Patients who had had one previous chemotherapy regimen were included, but 63% of patients were previously untreated. Six patients achieved complete remission and 11, a partial remission, for an overall response rate of 57%. Median remission duration was 22 months; median time to disease progression for all 30 patients was 8 months. Toxicity consisted of cyclic vaginal bleeding, hot flashes, weight gain, irritability, and fluid retention. This cyclic, sequential hormonal regimen was effective and well tolerated.
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PMID:Sequential cyclic combined hormonal therapy for metastatic breast cancer. 252 85


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