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

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

Human breast cancer ZR-75-1 cells expressed 1516 (105) (mean [S.D.]) interferon (IFN) receptors (IFNR) per cell with Kd of 0.61 (0.15) nmol/l. Oestrogen independent ZR-PR-LT and tamoxifen resistant ZR-75-9a1 8 mumol/l cells expressed similar numbers of IFNR. ZR-75-9a1 cells, which had been maintained in the absence of tamoxifen or known oestrogenic activity for 46 weeks, expressed a significantly higher number of IFNR (3170 [315]). Exposure of ZR-75-1 cells to 10(-9) mol/l 17 beta-oestradiol (E2) led to a consistent reduction in IFNR numbers whilst 10(-6) mol/l tamoxifen slightly increased IFNR expression. Since IFN increases oestrogen receptors in this cell line, IFN and E2 appear to have opposite effects on expression of each others' receptor. 10(-9) mol/l medroxy progesterone acetate and mifepristone significantly increased IFNR numbers whilst ORG 2058 decreased IFNR expression and ZK 98.299 had no effect. Progestin/antiprogestin induced IFNR increase in this cell line correlated with down-regulation of progesterone receptor (PR). Thus an IFN/ER/PR axis may exist in ZR-75-1 cells and variants.
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PMID:Modulation by oestrogen and progestins/antiprogestins of alpha interferon receptor expression in human breast cancer cells. 182 77

The emergence of resistant cells reduces the efficacy of many forms of drug therapy in human breast cancer. In order to understand some of the possible mechanisms by which hormonally dependent human breast cancers develop resistance to progestin therapy we have developed a human breast cancer cell line (5-RP) which is resistant to the growth inhibitory effects of progestins in culture. These cells routinely grow in 10 microM medroxyprogesterone acetate (MPA). The cell line was developed from T-47D-5 human breast cancer cells by stepwise selection in increasing concentrations of MPA. The progestin-resistant phenotype was relatively stable as assessed by the removal of MPA from the medium for varying periods of time. 5-RP cells passaged in the absence of MPA were still essentially insensitive to the growth inhibitory effects of MPA for at least 22 passages. Even at 53 passages out of the drug the 5-RP line was still less sensitive than the original T-47D-5 parent line. Transforming growth factor-alpha (TGF-alpha) and epidermal growth factor (EGF) receptor mRNA were both increased in the 5-RP line compared to the T-47D-5. Consistent with increased TGF-alpha expression, the EGF receptor measured by ligand binding was decreased. When the cells were removed from MPA, TGF-alpha expression declined gradually, but EGF-receptor mRNA levels increased, as did EGF-binding activity. These cells remained estrogen and progesterone receptor positive. Although progestins did not downregulate estrogen receptor expression, they did downregulate progesterone receptor expression in the 5-RP line. The progesterone receptor level of the 5-RP line, in the absence of MPA, was approximately 58% of that found in T-47D-5 cells, even after MPA had been removed for long periods of time. This decrease in receptor level was reflected in decreased ability to respond to progestins as assessed by the decreased ability of MPA to activate expression of both an endogenous gene (EGF receptor) as well as a transiently transfected progestin-responsive gene (MMTV-TK-CAT). Progestin resistance in the 5-RP cell line appears to be multifactorial, involving both increased growth factor expression and decreased receptor levels. It is likely, however, that these two aspects do not account entirely for the progestin-resistant phenotype and as yet other unidentified mechanisms may also be involved.
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PMID:Mechanisms involved in the evolution of progestin resistance in human breast cancer cells. 184 41

Progesterone-binding cyst protein (PBCP, identical to Gross Cystic Disease Fluid Protein; GCDFP-24) has been evaluated as a possible marker of differentiation in breast tissues. In 17 women with verified operable breast cancer, we have quantitated the cytosol content of PBCP, steroid hormone receptors (estrogen receptor[ER], progesterone receptor[PR] and androgen receptor[AR] as well as albumin in specimens from the primary tumor and from the adjacent non-malignant tissue of the same breast. A significantly higher amount of PBCP (p less than 0.001) and albumin (p less than 0.003) was found in the non-malignant tissue. Conversely, the content of steroid receptors was significantly higher (p less than 0.001) in the malignant tumor, compared to the non-malignant breast tissue. A significant correlation (p = 0.005) between PBCP content in the malignant tumor and in the non-malignant tissue was found. In malignant tissue, ER was significantly correlated with AR (p = 0.007) and to age at operation (p = 0.006). Our results are in agreement with recent reports on other tissue parameters, which indicate qualitative and quantitative differences between the malignant and the non-malignant counterpart with regard to regulation of cell growth and the expression of differentiation markers. This study provides evidence for PBCP as a marker of differentiation to be implemented in further clinical and basic research on breast cancer.
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PMID:Progesterone-binding cyst protein (PBCP = GCDFP-24) and steroid hormone receptors as markers of differentiation in breast cancer. Inverse relation of distribution in normal and malignant tissue of the same breast. 188 67

Progesterone receptors (PR) appear to be distributed in a heterogeneous way in mammary tumor cells. The study presented here was designed to examine if heterogeneity of PR expression is cell-cycle dependent. Immunofluorescence techniques were used to label PR on the MCF-7 human breast cancer cell line and image cytometry was used to analyze the PR expression during G0 (Ki-67 antigen-negative cells), G1, S, and G2/M cell-cycle phases. A second PR, BrdU, and DNA analysis was performed to study PR expression in the S-phase (BrdU-positive cells). Our results show that PR synthesis occurs preferentially during the G0-G1 transition and that PR levels are constant during the G1-G2 transition. The PR expression appears to be cell-cycle related and may therefore explain the heterogeneity of PR expression. However, the possibility that PR heterogeneity may be linked to the existence of PR-negative subclones cannot be ruled out.
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PMID:Image cytometry of progesterone receptor expression during the cell cycle in the MCF-7 cell line. 194 Mar 23

The present study demonstrates that the nature of the binding of estrogens to the hormone-binding domain of the estrogen receptor (ER) modifies the responses of estrogen-dependent cells. We report here that 10 nM estradiol (E2) forms noncovalent associations with the ER, increases the level of ER and Progesterone Receptors (PR) in ER+ MCF-7 human breast cancer cells in culture following short-term or long-term exposure to E2. In contrast, 10 nM 16-alpha-hydroxyestrone (16 alpha-OHE1), a physiological metabolite of E2, in short-term cultures is equivalent to E2, but upon long-term incubation, 16 alpha-OHE1 forms covalent associations with the ER, produces a marked decrease in ER and PR levels reaching values similar to, or below to that of control cells.
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PMID:Effects of estrogens on MCF-7 cells: positive or negative regulation by the nature of the ligand-receptor complex. 198 6

Progesterone-binding cyst protein (PBCP) is a secretory protein which has been found in varying concentrations and incidence in cytosols from benign breast tumors, primary breast cancer and metastasis. In order to evaluate its correlation to other prognostic factors, PBCP was analysed in tumor cytosols from 386 women with stage I and stage II breast cancer. The incidence of PBCP negative (i.e. PBCP = 0) tumors was significantly decreased in node negative patients as compared to node positive (p = 0.012). An inverse correlation between estrogen receptor content and PBCP was found (p = 0.001). In a multivariate analysis PBCP category was found to be an independent predictor of the likelihood of axillary nodal involvement (p = 0.015). In spite of this association, PBCP did not reach statistical significance as an independent prognostic factor with regard to relapse-free survival. To evaluate PBCP category as a possible predictive factor for response to adjuvant endocrine treatment, a subpopulation of node positive patients with ER positive tumors was analysed; in patients with PBCP negative tumors, adjuvant treatment with tamoxifen proved to increase the relapse-free survival significantly (p = 0.011). We suggest that PBCP may have a place among other biochemical parameters in breast cancer, to provide an extended basis for understanding of tumor biology and a better selection of patients for endocrine treatment.
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PMID:Progesterone-binding cyst protein (PBCP) in operable breast cancer: correlations with prognostic factors and predictive value for effect of adjuvant tamoxifen treatment. 206 14

The combined progestogen/estrogen oral contraceptive is the most common form of contraception in the US. They contain 1 of 5 synthetic progestogens (derived from 19-nortestosterone) and 1 of 2 estrogens. 3 new progestin compounds are in use in Europe and Asia. They are norgestimate, desogestrel, and gestodene. Estrogen seems to cause vascular complications. Progestin may cause atherosclerosis. Desogestrel and gestodene were studied for 6 months. They have little effect on glucose and lipid metabolism. Triphasal ethinyl estradiol/levonorgestrel and ethinyl estradiol/norethindrone (Ortho Novum 7/7/7) were compared in a 12-month prospective clinical trial. There seems to be no consensus of a pattern of increased breast cancer associated with oral contraceptive use. The UK National Case Control Study Group analyzed women younger than 36 years at the time breast cancer was diagnosed. 91% of their cohort had used pills. A significant trend was found when risk was analyzed with duration of taking pills. Women who had taken the pill for 4 years had no increased risk of breast cancer. However, there was an increased relative risk of 1.7 (P0.001) for women who took pills for more than 8 years. Among women using the pill for 8 years, the relative risk was 2.6 (p0.0001). AMong women using pills with 50 ug. of estrogen, the trend to increased risk was (P0.10). The 1988 National Survey of adolescent males showed that 60% of men never married were active sexually. Among 17- to 19-year-old-men who live in metropolitan areas, condom use has more than doubled, compared with 1979. In 1988, a "new" copper-containing IUD was approved for use in the US by the Food and Drug Administration, the Copper T 380 A. Pregnancy rates are less with this than with older devices. IUDs may cause pelvic inflammatory disease with resulting tubal infertility. However, the risk was overstated earlier. Women who have only 1 sexual partner in their lifetime had no significant risk of tubal infertility. "lost" IUDs continue to be a problem.
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PMID:Contraception. 210 26

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

The administration of MPA to virgin female BALB/c mice led to the development of mammary adenocarcinomas, which in further in vivo transplants gave rise to both MPA-dependent and MPA-independent lines. In this paper we chose one of the MPA-dependent lines with high contents of estrogen (ER) and progesterone (PR) receptors, and were able to demonstrate that a) the growth of these tumors could be manipulated by the administration or the withdrawal of the hormonal supply; b) PR were down-regulated in MPA-treated mice; c) progesterone had the same stimulatory effect as MPA on tumor growth; d) tumors did not grow in estrogen-treated mice; e) tumor growth was much lower in males than in females; f) the presence of the ovaries had a positive influence on tumor growth, even in the presence of MPA; g) the withdrawal of progestin pellets in ovariectomized mice usually led to complete remissions followed by regrowth of the tumors after several weeks; and h) the regrowing tumors maintained their steroid receptor pattern and (in 3 out of 4 cases) their hormone-dependent behavior in further passages.
Breast Cancer Res Treat 1990 Nov
PMID:Hormone dependence of a mouse mammary tumor line induced in vivo by medroxyprogesterone acetate. 215 68


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