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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

(MPA) Medroxyprogesterone acetate when employed at high doses (5001000 mg/day intramuscularly) can produce objective remission with improved survival in about 30% of postmenopausal women with advanced breast cancer resistant to cytotoxic drugs and endocrine therapies. When administered to women not previously treated with chemotherapy, the objective remission response rate reached 40%. From available evidence, high dose MPA can be considered a useful agent in the treatment of advanced breast cancer in postmenopausal women with soft tissue, pulmonary, pleural, or osseous involvement even when patients have become refractory to prior hormone and cytotoxic therapies. Early results suggest that the response rate can be increased in patients with estrogen-and/or progesterone-positive receptors. It is noteworthy that in a study conducted on postmenopausal women resistant to cytotoxic and/or hormonal drugs, the median duration of survival was 13.5 months, while CRs and PRs did not reach the median at 24 months after beginning MPA treatment. High dose MPA is essentially devoid of major side effects. Relief of pain, increase in appetite, and body weight, and sense of wellbeing are characteristic features of the improved quality of life under MPA treatment. However, a gluteal abscess (from 2-20% dose-related) is the most frequent side effect. A promising area for future studies is combined therapy using hormonal and cytotoxic agents or alternating sequential combinations. Well-designed studies are needed to develop means for increasing the complete response rate and therefore survival. Recent studies of combined chemotherapy and hormonal (MPA) therapy have yielded objective tumor regressions of 53-80% with an increased rate of complete remissions and duration of response. (Author's modified)
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PMID:High-dose medroxyprogesterone acetate (MPA) treatment in advanced breast cancer. A review. 39 Jul 98

Most oral contraceptives (OC) contain a progestin in combination with an estrogen, and the progestin component in OC includes one of the following 19-nortestosterone derivatives: norethynodrel; norethindrone; or norgestrel (levonorgestrel). It is well known that estrogens promote the growth of breast cancer. However, progestins have recently also been implicated in the development of breast cancer. We have compared and contrasted the ability of synthetic progestins to stimulate the proliferation of cultured human breast cancer cells and examined their possible mechanism of action. We found that some progestins used in OC were able to stimulate the growth of estrogen receptor-positive (ER+) MCF-7 and T47DA18 human breast cancer cells but not ER- MDA-MB-231, BT-20, and T47DC4 human breast cancer cells. However, two other progestins, MPA and R5020, which are not used in OC, were either not able to stimulate or only slightly stimulated growth. The potency of norethynodrel [median effective dose (EC50) = 4 x 10(-8) M] and norethindrone (EC50 = 3 x 10(-8) M) was greater than norgestrel (EC50 = 2 x 10(-7) M) in MCF-7 cells. E2 (EC50 = 8 x 10(-13) M) was an even more potent stimulator of growth. More importantly, the progestin-induced growth stimulation was blocked by the antiestrogens 4-hydroxytamoxifen and ICI 164,384 but not the antiprogestin 17 beta-hydroxy-11 beta-(4-dimethylaminophenyl)-17 alpha-(1-propynyl)-estra-4, 9-dien-3-one (RU486). To determine whether the proliferative action of progestins was mediated through the ER, cells were transfected with a chloramphenicol acetyltransferase reporter gene containing an estrogen response element derived from vitellogenin 2A gene. The progestins which stimulated the growth of breast cancer cells also increased chloramphenicol acetyltransferase activity. The induction of chloramphenicol acetyltransferase activity was blocked by the addition of the antiestrogens 4-hydroxytamoxifen and ICI 164,384 but not the antiprogestin RU486. This study provides direct evidence that the 19-nortestosterone derivatives in OC have estrogenic properties and suggests that activation of ER, but not progesterone receptor, is the growth-stimulatory mechanism for these synthetic progestins. Our results may help to explain the conflicting evidence linking OC and breast cancer risk. A rigorous evaluation of the "total" estrogenic potential of OC might produce a better correlation with breast cancer risk.
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PMID:Estrogenic potential of progestins in oral contraceptives to stimulate human breast cancer cell proliferation. 142

A 54 year-old female patient with disseminated breast cancer refractory to various kinds of previous therapies was treated with a combination therapy of 5'-DFUR, MPA and CPA. Partial response (PR) was obtained both against pleural and liver metastases with complete disappearance (CR) of soft tissue lesions and was still being continued for the following 7 months. No serious side effects were observed except for a mild degree of diarrhea and moon face. The patient was enjoying a favorable quality of life. We confirmed that this combination regimen was effective as the second line treatment for disseminated breast cancer.
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PMID:[Successful treatment of disseminated breast cancer with combination therapy of 5'-deoxy-5'-fluorouridine (5'-DFUR), medroxyprogesterone acetate (MPA) and cyclophosphamide (CPA)]. 153 Sep 5

In a randomised study 142 patients with advanced oestrogen-receptor-negative breast cancer in the tumour tissue received chemotherapy alone or chemotherapy combined with high doses (1000 mg daily) of oral medroxyprogesterone acetate (HD-MPA). Of the 126 fully evaluable for response, the response rates were 46% for chemotherapy alone and 73% for chemotherapy with HD-MPA (P = 0.005). There was no significant difference with regard to duration of response. Of the 138 patients evaluable for survival and toxicity, survival was shorter in the combined treatment group; median survival of 9 versus 13 months (P less than 0.05). Considerable toxicity was seen from HD-MPA, especially weight gain and fluid retention. The present study provides evidence that in concordance with preclinical studies an interaction between chemotherapy and HD-MPA may exist in breast cancer normally resistant to hormone therapy. The side-effects from MPA were substantial, however, and the survival data are of great concern.
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PMID:Chemotherapy with or without high-dose medroxyprogesterone acetate in oestrogen-receptor-negative advanced breast cancer. Norwegian Breast Cancer Group. 153 48

MPA induces mammary tumors in virgin BALB/c mice with an average latency of 52 weeks. In order to determine whether the simultaneous administration of a chemical carcinogen, N-methyl-N-nitrosourea (MNU), shortened the latency of MPA-induced tumors, a total of 60 virgin female BALB/c mice were treated with either MNU + MPA or MNU or MPA. The experiment lasted 7 months. The incidence and latency of mammary tumors were significantly different between the 3 groups: 15/19 (79%) in MNU + MPA-treated mice with a latency of 154 +/- 19 days; 3/20 (15%) in MNU-treated mice with a latency of 179 +/- 7 days; 0/20 (tumors only start appearing after 10 months) in MPA-treated mice. Histologically, MNU + MPA-induced tumors were similar to the few tumors observed in MNU-treated mice: most of them were type B adenocarcinomas with a high degree of necrosis and calcification. Only one of the MNU + MPA-induced tumors expressed high levels of ER and PR and proved to be MPA-responsive in further passages. All the other tumors showed low or non-detectable levels of ER and PR together with an independent pattern of tumor growth. In MNU-treated mice the only tumor that was transplanted proved to be hormone independent and had low levels of PR and ER. In both MNU and MNU + MPA treated mice lung adenocarcinomas were detected. Cystic uterine glandular hyperplasias were observed in all animals. It can be concluded that MPA and MNU potentiate their carcinogenic effect in mammary gland.
Breast Cancer Res Treat 1992 Jan
PMID:Mammary carcinogenesis induced by N-methyl-N-nitrosourea (MNU) and medroxyprogesterone acetate (MPA) in BALB/c mice. 155 89

The antiemetic response and side effects resulting from treatment with methylprednisolone (MPA) given on two different dose schedules were evaluated in 20 women with breast cancer who were undergoing chemotherapy consisting of cyclophosphamide, methotrexate and 5-fluorouracil (CMF). This randomized, crossover, double-blind study compared the antiemetic efficacy of a single dose of 125 mg MPN with that of two such doses. The study demonstrated the superiority of the latter protocol in preventing CMF-induced nausea and vomiting. The rate of antiemetic response to single vs double doses was as to follows: complete protection, 17% vs 30%; partial and minimal protection, 39% vs 55%; and no protection, 44% vs 15% of the courses, respectively (P = 0.0087). No difference in the antiemetic response rate was found between the first and the second course. Treatment with MPN was well tolerated, and no difference in the incidence of side effects was found between the single-dose and the double-dose schedule. We recommend the use of two doses of 125 mg MPN as prophylactic antiemetic treatment in breast-cancer patients receiving CMF chemotherapy.
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PMID:Methylprednisolone as antiemetic treatment in breast-cancer patients receiving cyclophosphamide, methotrexate, and 5-fluorouracil: a prospective, crossover, randomized blind study comparing two different dose schedules. 162 73

This study was designed to assess the multiple steroid receptor mediated activities of a series of synthetic 'progestins' on breast cancer cell growth, using the human ZR-75-1 cell line which possesses functional estrogen (ER), androgen (AR), and glucocorticoid (GR) receptors as well as progesterone (PgR) receptors. Four 17-hydroxyprogesterone derivatives (chlormadinone acetate, CMA; cyproterone acetate, CPA; medroxyprogesterone acetate, MPA; and megestrol acetate, MGA) and two 19-nortestosterone derivatives (norethindrone, NRE, and norgestrel, NRG) were thus investigated. Based on the requirement of estrogens for PgR-mediated antiproliferative effects and the reversal of PgR-mediated action by insulin, it was found that although all 'progestins' could inhibit ZR-75-1 cell growth through the PgR at low concentrations, the relative contribution of this receptor in cell growth control is highly variable between compounds. The quantitative importance of PgR-mediated inhibition of cell proliferation was inversely related to the amplitude of the androgenic effects induced by the compounds, the AR-mediated effects increasing in the order CPA less than MGA less than CMA less than NRE less than NRG less than MPA. The specificity of these androgenic effects is further supported by their reversal upon addition of the antiandrogen hydroxyflutamide. In addition, the 17-hydroxyprogesterone derivatives, but not the 19-nortestosterone derivatives, had glucocorticoid activities at high (micromolar) concentrations, as shown by reversal of growth inhibition by the antagonist RU486 in the presence of saturating concentrations of 5 alpha-dihydro-testosterone. All 'progestins' tested, except MPA and NRE, also had some antiglucocorticoid activity, NRG being the most potent in this respect. Finally, NRE and NRG exerted a marked mitogenic effect in estrogen-free medium which was clearly mediated through the ER as shown by the competitive reversal of their action by the steroidal antiestrogen EM-139. The present results show that growth measurements of the human breast cancer cells ZR-75-1 permit, with the appropriate steroid additions, the assay of progestin, androgen, estrogen, and glucocorticoid agonistic as well as antagonistic activities of test compounds. The present study shows, somewhat surprisingly, that while the AR is almost completely responsible for the action of MPA at low concentrations, the majority of the action of NRE, NRG, and MGA is also exerted through AR, while the androgenic action of CPA plays a lower role in the growth inhibition induced by this compound.(ABSTRACT TRUNCATED AT 400 WORDS)
Breast Cancer Res Treat
PMID:Multiple actions of synthetic 'progestins' on the growth of ZR-75-1 human breast cancer cells: an in vitro model for the simultaneous assay of androgen, progestin, estrogen, and glucocorticoid agonistic and antagonistic activities of steroids. 164 5

An advanced breast cancer patient refractory to CAF (Cyclophosphamide, Adriamycin, 5-fluorouracil), 5-FU-Methotrexate sequential therapy and Tamoxifen was treated with the combination 5' DFUR, MMC, Etoposide and MPA. Complete response was obtained both against liver and lymph node metastases from 7 months after the initial treatment. A mild bone marrow suppression and appetite loss were observed as the side effect. It is suggested that the combination therapy may be useful for previously treated patients with advanced breast cancer.
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PMID:[5'-deoxy-5-fluorouridine (5'-DFUR), mitomycin C (MMC), etoposide and medroxy progesterone acetate (MPA) in a previously treated patient with advanced breast cancer]. 182 14

Ten patients with recurrent pleural effusions due to advanced cancer were treated by intracavitary methylprednisolone acetate (Depo-Medrol [DM], Upjohn, Kalamazoo, MI). They received one to six courses of DM (median, three courses per patient) with doses ranging from 80 to 160 mg per course. Effusion cells were cryopreserved before and during DM installation for subsequent determination of ploidy by flow cytometry. Pleural effusion in all three patients with advanced breast cancer resolved and did not reaccumulate throughout follow-up for 11+, 10+, and 8+ months. Pleural effusion in a patient with metastatic gastric cancer and in two of four patients with adenocarcinoma of unknown origin partially resolved. Altogether six of ten patients (60%) subjectively and objectively benefited from this therapy. All patients tolerated the treatment well with no local or systemic side effects. Flow cytometry showed a reduction in ploidy of effusion cells in all three patients with breast cancer, from a peak mean channel of 6C to nearly 2C after therapy. Transient reduction of ploidy was seen also in the effusion of a patient with unknown primary tumor associated with clinical improvement. The clinical and laboratory data reported offers initial evidence that DM when instilled into the pleural cavity after incomplete thoracentesis may act as effective palliative therapy either alone or in combination with other anticancer agents.
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PMID:Clinical and flow cytometry characteristics of malignant pleural effusions in patients after intracavitary administration of methylprednisolone acetate. 204 56

The efficacy and side-effects of megestrol acetate and medroxyprogesterone acetate in postmenopausal patients with advanced breast cancer were compared in a prospectively randomized study. The dosage of MA was 2 X 80 mg p.o. or MPA 2 X 500 mg p.o. daily, given as a secondary hormonal treatment, mostly after previous treatment with tamoxifen. Ninety-eight patients entered the study and 92 were evaluable for effect, 48 patients on MA and 44 on MPA. Age, main tumor site and prior treatment were not different, but there was a preponderance of ER-negative tumors in the MA group. Responses appeared to be more frequent in the MPA-treated group (25% vs. 43%), predominantly in bone lesions, 12% for MA and 45% for MPA. Median progression-free survival was comparable, 15 vs. 10 months, and overall survival was not different (20 vs. 16 months). Toxicity was frequent, occurring in 83% vs. 74% of patients: increased appetite, nausea and dizziness in more than 20%, and a preponderance of pyrosis and breathlessness on MA and hot flashes, sweating and tremors on MPA. Cushingoid symptoms were present in about a quarter of the patients treated for more than 3 months. The occurrence of thrombo-embolic episodes and cardiovascular events was evenly distributed. Patients on MPA had more often increase in body weight, systolic blood pressure and serum creatinine than those treated with MA. It is concluded that MPA may be more effective for treatment of bone metastases, at the expense of more progestational side-effects. The occurrence of Cushingoid effects is frequent but similar in both arms, while the incidence of cardiovascular or thrombo-embolic events cannot be related to the use of either compound.
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PMID:A randomized comparison of megestrol acetate (MA) and medroxyprogesterone acetate (MPA) in patients with advanced breast cancer. 214 91


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