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

The modalities used to treat 27 male patients with metastatic breast cancer at Memorial Hospital from 1957--1979 are reviewed. The overall objective orchiectomy response rate was 48% (11/23). The median response was 11 months (6--96 months). The median survival in responders was 58 months, whereas the median survival in orchiectomy failures was 24 months. Four patients had estrogen receptor protein determinations (ERP). Two positive ERP patients and one borderline ERP patient responded (18--34 months). One ERP-negative patient failed orchiectomy. The number of major ablations in this series (two responses/two adrenalectomies, two failures/two hypophysectomies) does not permit conclusions, although review of the literature suggests that major ablation may be valuable in patients responding to orchiectomy. Two of three patients who refused ablative therapy responded (three months, ten months) to single agent provera. Administering stilbesterol to the ten-month responder and to the patient who failed provera resulted in two additional responses (four months, continuing, and 22 months). Of six patients who failed orchiectomy and subsequently received chemotherapy, four patients responded (7--40 months). The median survival in these patients was 40 months (33--44 months). This review supports the importance of orchiectomy in the treatment of metastatic male breast cancer. Although the numbers are small, these data suggest that estrogen receptor determinations may be useful in selecting patients for orchiectomy. Selective additive hormone therapy may be useful in patients who refuse orchiectomy. Chemotherapy may provide worthwhile palliation in patients who fail orchiectomy.
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PMID:Treatment of advanced male breast cancer. 616 79

In unselected populations of women, the progestins medroxyprogesterone acetate (MPA) and megestrol acetate (MA) have produced response rates of 14% to 31% in metastatic breast cancer, sparking new investigative activity to define their proper role. One proposed mechanism of action for progestins is that they interfere with replenishment of the cytoplasmic estrogen receptor. Although not binding to estrogen receptors, progesterone has been shown to decrease the quantity of estrogen receptor in target tissue. Prediction of response of metastatic breast cancer to progestins largely follows the conventional rules established for the selection of additive hormonal therapy. Little difference is seen between appropriate doses of MPA and of MA in reports of prognostic factors associated with tumor response. The presence of hormone receptors in tumor tissue may be the most significant predictor for response to progestins. Tumors that contain both estrogen and progesterone receptors will respond to progestins in over 61% of instances, whereas those with only one type of hormone receptor will respond 20% to 30% of the time. Response to MPA or MA is probably independent of the presence of progesterone receptor. Response rates to MA of around 30% have been noted in patients who had previously responded to tamoxifen and then progressed. Previous exposure to chemotherapy does not appear to jeopardize chances for response to MA. A limited number of randomized trials of tamoxifen versus MA show no significant response difference between the two therapies in breast cancer patients with similar prognoses.
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PMID:The role of progestins in the treatment of breast cancer. 623 Jul 22

A study was made of basic mechanisms involved in regression of breast cancer exposed to high levels of synthetic progestins. The possibility that progestins act on breast cancer by way of the progesterone receptor mechanism and subsequent increase of estradiol 17 beta-dehydrogenase activity could not be confirmed in this investigation. It is demonstrated that the progestins megestrol acetate and medroxyprogesterone acetate are strong competitors for steroids which bind specifically to androgen, glucocorticoid, and progesterone receptors, indicating that the progestins are able to bind to these receptors with high affinity. In contrast, these progestins do not compete with estradiol for estrogen receptor binding. In 34 patients with progressive metastatic breast cancer, results of receptor studies have been correlated with clinical response during treatment with megestrol acetate. Statistically, regressions were significantly associated with tumors containing large amounts of androgen receptors. Clinical correlation with the quantities of glucocorticoid receptor was weak, while such correlations with estrogen and progesterone receptors were absent. However, we did demonstrate relationships between the quantities of the various receptors in breast cancer. Tumors containing a large amount of androgen receptors also generally contain estrogen receptors. It might be that a favorable response to progestins is confined to the group of patients with hormone-responsive breast cancers, as such characterized by the presence of estrogen receptors, and that within this group the actual androgen receptor levels determine response.
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PMID:Estrogen, androgen, glucocorticoid, and progesterone receptors in progestin-induced regression of human breast cancer. 624 8

Fifty to sixty percent of postmenopausal women with estrogen receptor positive metastatic breast cancer respond objectively to surgical ablation of the pituitary or adrenal glands. Several investigators have recently developed medical alternatives to surgical ablative therapy for these patients. This review describes one of these strategies, the inhibition of estrogen synthesis with the enzyme inhibitor aminoglutethimide (AG). Aminoglutethimide blocks several cytochrome P-450-mediated steroid hydroxylation steps including those required for cholesterol to pregnenolone conversion and for the aromatization of androgens to estrogens. In women with metastatic carcinoma, a regimen including 1,000 mg of AG and 40 mg of hydrocortisone as replacement glucocorticoid was administered daily. Clinical studies revealed a 32% objective response rate to AG-HC in unselected patients, and a 52% response in women with estrogen receptor positive tumors. Randomized trials revealed that AG-HC produced objective regression as frequently as surgical adrenalectomy (Ag-HC + 53% vs. surgical adrenalectomy (43%, p = NS), and as surgical hypophysectomy (AG-HC 47% vs. hypox 21%, p + NS). Comparison of AG-HC administration with antiestrogen treatment suggested an equal rate of response to either therapy. Preliminary data document responses to AG in antiestrogen-resistant patients. Current studies do not allow precise recommendations regarding the sequence of use of antiestrogens and AG-HC.
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PMID:Suppression of estrogens with aminoglutethimide and hydrocortisone (medical adrenalectomy) as treatment of advanced breast carcinoma: a review. 629 27

Complete remissions in patients with metastatic breast cancer using endocrine therapy or chemotherapy are infrequent. Breast tumors are known to be heterogeneous with respect to estrogen receptor status, and the low complete remission rate may be related to this biochemical heterogeneity. Based on laboratory experiments using human breast cancer cells in tissue culture, a phase II protocol was designed using tamoxifen, premarin, methotrexate, and 5-fluorouracil. Thus far, twenty-nine (29) patients have been entered into this study and twenty-five (25) are currently evaluable for response. Overall response rate was 72%, and 14 of 25 (56%) attained a complete remission. Toxicity was minimal. Median nadir white blood cell count was 5,800 and median nadir platelet count was 252,000. In summary, this combination chemo-hormonal therapy regimen is effective with a more than 50% complete remission rate and minimal toxicity.
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PMID:A phase II trial of tamoxifen, premarin, methotrexate and 5-fluorouracil in metastatic breast cancer. 629 30

Fifty-five patients with newly diagnosed, estrogen receptor negative, metastatic breast cancer were entered in a trial of mitoxantrone, 10 mg/m2 intravenous (IV), cyclophosphamide, 500 mg/m2 IV, and 5-fluorouracil, 1000 mg/m2 IV, which were given on day 1 of a 21-day treatment interval. This trial was designed to test the efficacy of substituting mitoxantrone for doxorubicin as part of a combination that has proved to be effective in inducing remission. The trial was also intended to evaluate the response of resistant disease and of stable metastatic disease to a combination of doxorubicin and vinblastine sulfate. The cardiotoxic potential of mitoxantrone was evaluated in all the patients by serial measurements of ejection fraction and by endocardial biopsy of the right ventricle. Patients who achieved a complete response or a partial response (with bone as the only site of disease) on the three-drug combination were continued on this treatment for 2 years, or for 1 year following a complete response, whichever was shorter or as cardiac monitoring permitted. Therapy with doxorubicin, 25 mg/m2/d for two days, followed by continuous infusion vinblastine sulfate, 1.4 mg/m2/d for four days, was given to all patients who progressed after two courses or were stable after six courses of three-drug therapy. The preliminary results from 50 patients show that 4 attained a complete response and 30 a partial response, giving a total response rate of 68%. The median duration of response was more than 7 months (range greater than 5 to greater than 15 months). One patient in complete remission relapsed after 8 months and failed reinduction therapy with doxorubicin-vinblastine sulfate. Myelosuppression, principally granulocytopenia, was the major side effect of cyclophosphamide-mitoxantrone-5-fluorouracil. Mild to moderate vomiting occurred in 76% of patients and alopecia in 88%. This therapy was discontinued in four patients because of a decreased cardiac ejection fraction and/or symptoms of heart failure. No cardiac biopsy score, however, has been greater than 1.0. These results suggest that a combination of cyclophosphamide-mitoxantrone-5-fluorouracil is effective in untreated, estrogen receptor negative, metastatic breast cancer and is comparable to the doxorubicin combination. Myocardial injury occurs with mitoxantrone, and a safe cumulative dose has yet to be established.
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PMID:Mitoxantrone, cyclophosphamide, and 5-fluorouracil in the treatment of hormonally unresponsive metastatic breast cancer. 638 62

Cytoplasmic estrogen receptor (ERC), nuclear estrogen receptor (ERN), and cytoplasmic progesterone receptor (PRC) were studied in 217 human breast cancers. ERC was found in 48.4%, ERN in 37.8%, and PRC in 32.7%. Histological grade was significantly correlated with ERC, ERN and PRC. Well-differentiated tumors were more frequently positive for the receptors while poorly differentiated tumors were generally negative for the receptors. Seventy one percent of the most differentiated tumors were ERC(+) ERN(+) PRC(+) and ERC(+) ERN(+) PRC(-). The histological grading system consists of tubule formation, nuclear pleomorphism and mitotic activity. There were significant correlations of receptor contents with nuclear pleomorphism and more mitotic activity. This was also confirmed by the study on the relationships between receptor contents and thymidine labeling index or mitotic index. The possibilities of receptors decreased with an increase in nuclear diameter. And there was a significant correlation between the receptor contents and the numbers of intracellular organellas in ultrastructural features of breast cancer cells. Among 33 cases of advanced or metastatic breast cancer submitted to endocrine therapy, 13 cases showed clinical response (CR or PR) These cases were both ERC and ERN positive independently of PRC status. Therefore, it is suggested that hormone receptor may be used as an independent prognostic factor in breast cancer.
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PMID:[Estrogen receptor in human breast cancer: relationship between the receptor contents and the histological and cytomorphological characteristics]. 649 99

The antiestrogenic agent tamoxifen was evaluated in 17 pre- and 103 postmenopausal women with recurrent or metastatic breast cancer at two dose levels (2 and 3 x 10 mg daily). Dose-related differences in the results were not observed. Altogether 49.2% of these patients responded to therapy (10% complete remissions, 9.2% partial remissions, 30% no change). While a response rate of 52.5% was found in the postmenopausal group, the rate was markedly worse in premenopausal women (29.4%). In postmenopausal patients there was a poorer remission rate in older women. Regarding the dominant site of lesions, the best results were achieved in patients with lung and pleural metastases, followed by soft tissue metastases. Patients with a disease-free interval of more than 100 months responded better to therapy than those with a shorter interval. Long-term results were much more favorable in patients who primarily responded to tamoxifen than in nonresponders. As the most valuable prognostic criterion, the hormone receptors were assayed. 75% of the estrogen receptor (ER) and progesterone receptor (PgR) positive and 55,6% of the ER-positive and PgR-negative patients derived benefit from this treatment in contrast to only 19% of the ER- and PgR-negative women. Plasma levels of estradiol, progesterone, testosterone, and FSH were not changed by tamoxifen, but average cortisol and prolactin concentrations were altered significantly. A short-time increase of the prolactin level 2 weeks after onset of tamoxifen treatment and a decrease thereafter also seem to be good prognostic signs. Side effects were few and did not occur more severely or frequently in the higher dose group.
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PMID:[The antiestrogen tamoxifen in advanced breast cancer (author's transl)]. 677 66

In this study of 59 postmenopausal patients with metastatic breast cancer, the therapeutic effect of tamoxifen (TAM) and/or TAM plus medroxyprogesterone acetate (MPA) was investigated and its effectiveness was related to the patients estrogen receptor (ER) levels. 3 studies are discussed: 1) Study 1, in which TAM was used alone; 2) Study 2, in which TAM was tested against TAM+MPA; and 3) Study 3, in which TAM was tested against TAM+diethylstilbestrol (DES). In this unselected population of post menopausal patients with metastatic breast cancer, the overall response rate to TAM treatment was 80% (12/40). Of 21 ER positive patients, 10 (48%) responded to TAM therapy. The ER values of these patients were significantly higher than the ER values of nonresponders (P .001), but no correlation was found between the ER value and the duration of remission in TAM-treated patients. These results are from the population of Studies 1 and 2; Study 3's population was too small for significant findings to be reported.
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PMID:Therapeutic effect of tamoxifen related to estrogen receptor level. 698 11

Seventy-three women with metastatic breast cancer were treated with aminoglutethimide and dexamethasone. No complete responses occurred. Ten patients (16%) achieved partial responses (mean duration, 12 months). The proportions of patients responding by disease site were breast (50%), nodes (33%), skin (23%), bone (16%), lung (11%), and liver (7%). Response did not correlate with age, menopausal status, performance status, or cortisol suppression. Ninety percent of responders had had previous responses to hormonal manipulations. No responses occurred in estrogen receptor negative patients. An additional 20% of patients had disease stabilization of eight or more months (mean, 17 months). Severe bone pain was present in 47 patients and was relieved in 19. Side effects occurred in 75% but caused discontinuation of therapy in only four patients. Somnolence, nausea, rash, Cushings syndrome, and leukopenia were the most frequent side effects. Aminoglutethimide with dexamethasone is an effective hormonal treatment for metastatic breast cancer.
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PMID:Treatment of metastatic breast cancer with aminoglutethimide. 722 90


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