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

Twenty-two oophorectomized or postmenopausal women with metastatic breast cancer resistant to several medical therapies (tamoxifen, or other endocrine therapy, and chemotherapy) were treated in a first trial with 200 mg per day of RU486 for 1 to 3 months. The long-term tolerance was good but there was a moderate decrease in plasma potassium. Plasma cortisol was increased 2-fold without clinical hypo- or hypercorticism. Twelve patients had a partial response or a stabilization of secondary deposits for 6 weeks but the response rate at 3 months was 18%. When available, estrogen and progesterone receptor levels were positive in these patients. This preliminary trial shows for the first time that the antiprogestin RU486 is well tolerated for medium term treatment. It suggests that it might be active on advanced breast cancer becoming resistant to tamoxifen.
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PMID:The antiprogestin RU486 in advanced breast cancer: preliminary clinical trial. 331 Dec 38

Estrogen receptor (ER) and progesterone receptor (PgR) levels have been reported to have prognostic significance with respect to disease-free survival in early-stage breast cancer patients. The current retrospective study was undertaken to determine whether ER and PgR levels, as well as other potential prognostic factors, might be related to a progression-free interval (PFI) during additive hormonal therapy in advanced-stage breast cancer patients. Eligibility requirements for this study included the following: histologically confirmed recurrent or metastatic breast cancer, known quantitative ER and PgR levels, postmenopausal status, treatment with either megestrol acetate or tamoxifen, and Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2. The characteristics of the 105 patients included in these analyses were as follows: median age, 62 years; median disease-free interval (DFI), 523 days; median ER level, 44 fmol/mg; median PgR level, 52 fmol/mg; soft tissue-dominant disease, 37 patients (35%); bone-dominant disease, 36 patients (34%); visceral-dominant disease, 32 patients (31%); one site of disease, 60 patients (58%); two or more sites of disease, 45 patients (42%); treatment with megestrol acetate, 62 patients (59%); treatment with tamoxifen, 43 patients (41%). All of the independent variables listed immediately above were included in a multiple linear regression analysis in which PFI, expressed as log PFI, was the dependent variable. In this analysis, a positive linear relationship was observed between log PFI and the following independent variables: log ER, log PgR, and age (r2 = 0.329). An alternative model (r2 = 0.350) was derived, in which previous treatment with chemotherapy was negatively related to log PFI. However, it appears that previous treatment with chemotherapy could be a "proxy variable," because patients who had been treated with chemotherapy previously were significantly younger and had significantly lower ER (P = 0.0001) and PgR levels (P = 0.0004). None of the other independent variables were included in these models. If the assumption that PFI is a measure of the effectiveness of hormonal therapy is true, these results suggest that quantitative ER and PgR levels and age supersede other traditional predictor variables in predicting the hormonal responsiveness of individual breast carcinoma.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Quantitative estrogen and progesterone receptor levels related to progression-free interval in advanced breast cancer patients treated with megestrol acetate or tamoxifen. 336 97

One hundred twenty-four patients with recurrent or metastatic breast cancer were randomized to receive megestrol acetate 40 mg orally, four times daily, or tamoxifen 10 mg orally twice daily. If therapy failed patients were crossed over to the alternate treatment. Eligibility required that either the estrogen or progesterone receptor be positive or that both values be unknown, and that patients be at least 2 years postspontaneous menopause or over 50 years of age. Pretreatment characteristics were similar for both groups. Three patients had had previous hormonal therapy while one third had had chemotherapy. Objective response for evaluable patients based on strict UICC criteria was 29% with megestrol acetate and 31% with tamoxifen. Responses in patients with bone and soft tissue disease were similar for both regimens; however, 7 of 19 (37%) patients with visceral disease responded to tamoxifen but none of 18 (0%) responded to megestrol acetate. Response did not correlate with amount of estrogen or progesterone receptor. Unadjusted analysis of time to progression and survival showed no significant differences between regimens. With adjustment for pretreatment characteristics, patients on tamoxifen had a statistically significant prolongation of both of these parameters. Crossover data show 3 of 24 patients responding to tamoxifen after failure on megestrol acetate and 1 of 24 responding to megestrol acetate after failure on tamoxifen. However, crossover data should be viewed cautiously, as patients who are currently responding to initial treatment are those who would be most likely to respond to crossover therapy.
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PMID:Megestrol acetate v tamoxifen in advanced breast cancer: a phase III trial of the Piedmont Oncology Association (POA). 388 3

Metastatic breast cancer frequently presents as a malignant pleural effusion. Knowledge of the estrogen and progesterone receptor status of the tumor predicts response to hormonal therapy, but breast cancer tissue in the pleural space is not readily accessible for hormone receptor determination. Thoracoscopy was used in six breast cancer patients with pleural effusions; all but one had concurrent sites of metastases. In five of six women recurrent breast cancer in the pleural cavity was diagnosed by thoracoscopy, and in four sufficient tissue was obtained for receptor assay. All patients achieved excellent control of their pleural effusions through a combination of local sclerotic measures and systemic therapy. Thoracoscopy is a safe procedure that can be performed under local anesthesia and is useful to visualize the pleural space, not only for diagnosis but also for obtaining breast cancer tissue for hormone receptor determination.
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PMID:Pleural effusion in breast cancer. Thoracoscopy for hormone receptor determination. 394 64

Creatine kinase BB serum levels were evaluated by radioimmunoassay in patients with benign or malignant breast pathology. Elevated enzyme levels were observed in 6 out of 20 (30%) patients with primary breast cancer. After surgery the levels fell to normal values only in patients without nodal involvement. Six out of 28 (21%) patients with benign breast lesions and 4 out of 38 (13%) patients with metastatic breast cancer also showed increased levels of the enzyme. Most of the patients with high creatine kinase BB serum levels were found to have estrogen and progesterone receptor-positive tumors. These findings suggest that creatine kinase BB can barely be considered a marker of malignancy in breast pathology, but rather an indicator of hormone dependency in breast cancer.
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PMID:Elevated serum levels of creatine kinase BB in breast cancer. 397 93

Postmenopausal patients with metastatic breast cancer were treated with medroxyprogesterone acetate (MPA) (Clinovir) in dosages between 500 and 1500 mg orally per day. The relation of MPA plasma concentrations and endocrine effects were studied in a longitudinal fashion. MPA exerted suppressive effects on the basal and gonadotropin-releasing hormone (GnRH) stimulated gonadotropin secretion, cortisol, dehydroepiandrosterone (DHEA), and estradiol (E2) in a dose-dependent manner leading to a complete suppression with 1500 mg orally per day. The depression of thyroid hormones (T3 and T4) coincided with a depression of the thyroxine-binding index (TBI). MPA did not affect human growth hormone (hGH), basal and thyrotropin-releasing hormone (TRH) stimulated thyroid-stimulating hormone (TSH) and aldosterone. Basal and TRH-stimulated prolactin (PRL) secretion showed a slight but distinct elevation. From these data it is concluded that in postmenopausal patients MPA exerts its antitumor activity by an interference with the hypothalamo-pituitary adrenal axis in the sense of a selective pharmacologic hypophysectomy leading to complete suppression of adrenal steroid secretion. Additionally, MPA inhibits tumor cell growth through the progesterone receptor. A dual mechanism for the antitumor activity of high dose is postulated MPA: ablative through suppression of the hypothalamo-pituitary-adrenal axis and subsequent estrogen deprivation, and additive via the progesterone receptor directly on the tumor cell. The significance of gonadotropin suppression in the postmenopause for breast cancer growth is unclear. The depression of T3 and T4 is due to a depression of thyroid hormone-binding proteins. The elevation of PRL secretion may be explained by a slight estrogenic activity of MPA metabolites.
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PMID:Pharmacokinetic and pharmacodynamic basis for the treatment of metastatic breast cancer with high-dose medroxyprogesterone acetate. 608 20

Based upon preliminary observations that tumor response to MPA was correlated to cortisol suppression 42 patients were treated with MPA at different dose levels. 1500 mg MPA p.o. almost completely suppressed endogenous cortisol production in 23 out of 23 patients. Consequently, 51 patients with advanced stage metastatic breast cancer were treated with Medroxyprogesteroneacetate (HD-MAP) at a dosage of 1500 mg p.o. daily or 500 mg i.m. on 5 days per week. There were 5 complete and 7 partical remissions, 23 patients with no change and 10 with progressive disease. 7 patients were not evaluable. Clinical results correlated to plasma cortisol and prolactin blood levels bot not to LH, FSH, TSH, TBI, T3, T4, ACTH and aldosterone measurements. There was no patient with relapse and suppressed cortisol or normal prolactin measurements. The development of pituituary resistance to MPA is suggested. HD-MPA was equally effective in estrogen and/or progesterone receptor positive as in receptor negative patients. It is proposed that cortisol and prolactin determinations are useful to monitor for effective MPA treatment and the early detection of MPA resistance.
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PMID:[High dose medroxyprogesteroneacetate in metastasizing breast cancer: correlations between course of the disease and hormone profiles]. 622 46

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

Optimum conditions were established for preparation of nuclei from human breast cancer biopsies. Incubation of nuclei with various concentrations of L-3,3',5-[125I]triiodothyronine showed the presence of three binding systems: a high-affinity binding system (type I) (KD approximately 0.5 micro M); an intermediate-affinity saturable system (type II) (Kd approximately 0.5 micro M)p and a nonsaturable nonspecific system. Salt at high concentrations (0.4 M-KCl) extracted only type I triiodothyronine-binding protein, thus simplifying its study and quantification. Type I binding protein was shown to have the affinity for triiodothyronine and the hormonal specificity usually ascribed to thyroid hormone receptors. Its sedimentation coefficient was 3.6S at 0.4 M KCl. Extractable triiodothyronine receptors was measured in 58 individual biopsies of primary and metastatic breast cancer. It was present in all tumors, but its concentration was highly variable (average, 0.20 pmol/mg DNA; range 0.044 to 0.702). Triiodothyronine receptor concentration was not correlated with age or endocrine status of the patient or with extension or histological grading of the tumor. Moreover, there was no correlation with estradiol and progesterone receptor concentration.
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PMID:Thyroid hormone receptors in human breast cancer. 626 37


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