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

We studied cellular proliferation by measuring the tritiated thymidine labeling index (TLI) in slices of primary invasive breast carcinomas. Estrogen receptor (ER) and progesterone receptor (PgR) were measured by ligand-binding assay. The TLI was a strong independent predictor of survival and relapse-free survival in women with or without axillary lymph nodal metastases and in American Joint Committee stage I. In operable node-negative women treated surgically, predicted survival at 5 years was 89 +/- 4% (probability +/- standard error) for 81 patients with low TLI (less than or equal to 3%), 64 +/- 7% for 101 with mid TLI (3.1-8%), and 66 +/- 6% for 86 with high TLI (greater than 8%) (P = 0.001). Probabilities of survival for patients with positive axillary nodes were 79 +/- 6% for 86 with low, 71 +/- 7% for 71 with mid, and 52 +/- 6% for 89 with high TLI (P = 0.0002). In stage I patients (tumor diameter not exceeding 2 cm), 5-year survival probabilities were 93 +/- 4% in 70 with low, 72 +/- 8% in 43 with mid, and 58 +/- 10% in 35 with high TLI, (P = 0.0005). The TLI was predictive for survival and relapse-free survival within subgroups positive and negative for ER and positive for PgR (P less than 0.05) in stage I patients, and a predictive trend was observed in the PgR-negative subgroup (P = 0.16). TLI also predicted within different categories of vascular invasion and nuclear grade. A stepwise Cox proportional hazards model selected TLI, number of positive axillary lymph nodes, and maximum diameter of the breast carcinoma as independent variables predictive of relapse, and added ER as a fourth variable for prediction of survival.
Breast Cancer Res Treat 1988 Oct
PMID:Proliferative index of breast carcinoma by thymidine labeling: prognostic power independent of stage, estrogen and progesterone receptors. 324 48

The authors evaluated the ability of a monoclonal antibody immunoperoxidase procedure (ERICA [Estrogen Receptor Immunocytochemical Assay], information from Regulatory Affairs Department, Abbott Laboratories, North Chicago, IL) to detect estrogen receptor in aspiration biopsy cytology (ABC) specimens from breast cancer routinely taken by fine-needle aspiration during office diagnostic evaluation. Results were correlated with biochemical values determined from dextran-coated charcoal (DCC) assay on tumor tissue obtained subsequently at operation. ERICA had positive results in 32 of 41 DCC-positive cases (sensitivity, 78%) and in 5 of 17 DCC-negative cases (specificity, 71%). The semiquantitative degree of ERICA positivity correlated with the concentration of estrogen receptor by DCC. Results of both assays correlated with the histologic grade of the tumor and patient age. Estrogen receptor can be determined by immunocytochemistry in ABC specimens in a community hospital. However, the sensitivity and specificity of this procedure compared with biochemical assay, and eventual response to hormonal therapy, require further investigation.
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PMID:Determination of estrogen receptor by monoclonal antireceptor antibody in aspiration biopsy cytology from breast carcinoma. 327 43

The paper presents interim results of an on-going randomized trial of adjuvant tamoxifen (40 mg daily for 2 years) versus no endocrine adjuvant therapy in postmenopausal women with early breast cancer. A total of 1407 patients were included in the study between November 1976 through June 1984. Estrogen receptor (ER) data were available on 1184 patients (84%). The median follow-up was 53 months. Adjuvant tamoxifen increased the recurrence-free interval (P less than 0.01) but had no significant effect on overall survival. Treatment failures were reduced by 25% (P less than 0.01) and deaths by 7% (P greater than 0.05). Tamoxifen mainly decreased the frequency of loco-regional recurrence whereas distant metastases were less affected. The treatment effect was independent of tumor stage but was significantly related to the estrogen receptor (ER) content of the primary tumor. Tamoxifen appeared ineffective among ER negative patients, and the greatest effect was seen among those with high levels of ER. The results indicate that the main mechanism of action of adjuvant tamoxifen is similar to that suggested in advanced disease, i.e. an interaction with the estrogen receptor.
Breast Cancer Res Treat 1987 Dec
PMID:The Stockholm trial on adjuvant tamoxifen in early breast cancer. Correlation between estrogen receptor level and treatment effect. 332 86

To ascertain the role of estrogen (ER) and progesterone (PR) receptors as prognostic indicators of resectable breast cancer, the records of 204 patients were analyzed whose receptor studies were done at the Maimonides Medical Center from 1975 to 1983. All patients had radical or modified radical mastectomies and did not show any evidence of distant metastases at the time of operation. Median follow-up was 37 months. An additional 117 patients received some form of adjuvant therapy, mainly chemotherapy, and were analyzed separately. Life table analysis using the log rank test for measuring significance, and a Cox multivariate analysis was performed. At 48 months, 22% of the ER positive (ER+) group versus 33% of the ER negative (ER-) group had recurred as compared to 16% and 35% for the PR+ versus PR- groups, respectively. Life table analysis of the disease free interval (DFI) showed that the difference between the ER+ and ER- groups was not significant (p greater than 0.1), while the difference in DFI between the PR+ and PR- groups was significant (p less than 0.05). Multivariate analysis revealed that the most important factors in predicting the DFI were nodal status (p less than 0.001), tumor size (p less than 0.025), and progesterone receptor status (p less than 0.05). Estrogen receptor status was not found to be significant. In conclusion, PR- patients have a shorter DFI than PR+ patients and that PR status is a more valuable predictor of DFI than ER status.
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PMID:Relationship of estrogen and progesterone receptors to prognosis in breast cancer. 333 66

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

It has been proposed that proteases secreted by cancer cells facilitate metastasis by degrading extracellular matrix. Estrogen receptor-positive breast cancer cells secrete a Mr 52,000 pro-cath-D under estrogen stimulation, whereas this protease is produced constitutively by estrogen receptor-negative cancer cells. We report on the degradation in vitro of extracellular matrix by purified Mr 52,000 cathepsin D (cath-D) and by conditioned media prepared from different cell lines. The purified Mr 52,000 pro-cath-D was autoactivated at pH 4.5 into a Mr 51,000 cath-D and found to digest the extracellular matrix of endothelial bovine corneal cells labeled with [3H]proline or [35S]methionine. Culture medium conditioned by estrogen-treated MCF7 cells had a similar effect at pH 4.5 but not at pH 7.4. Matrix degradation was totally inhibited by pepstatin. Other breast cancer cells (BT20, MDA-MB231, T47D cells, etc.) and other cancer cells also secreted a pepstatin-sensitive proteinase able to degrade extracellular matrix. By contrast, the U2 variant of MCF7 cells, which lacks the Mr 52,000 cath-D gene, and the nontumoral epithelial mammary cells secreted a negligible amount of this proteinase. In all conditioned media, the pepstatin-dependent extracellular matrix degrading activity was highly correlated to the Mr 52,000 cath-D concentration measured by immunoenzymatic assay. We conclude that the Mr 52,000 cath-D is the major acidic protease secreted by mammary cancer cells. We suggest that this protease may degrade basement membrane and consequently facilitate tumor invasion when it is released in an acidic microenvironment.
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PMID:In vitro degradation of extracellular matrix with Mr 52,000 cathepsin D secreted by breast cancer cells. 337 11

Estrogen receptor status, tumor histology, and the interval between the development of tumors were assessed in 99 patients with bilateral breast cancer. Tumors were first grouped into those simultaneously detected in both breasts or within 12 months of each other (synchronous bilateral breast cancer, of which there were 64) and second, those detected within more than 12 months of each other (asynchronous bilateral breast cancer, of which there were 35). Nineteen percent of all tumors were lobular carcinomas. Overall, the rate of receptor discordance between the two tumors was not significantly different from that previously reported between biopsies of primary tumor and metastases in patients with unilateral breast cancer. Synchronous receptor-positive tumors occurred significantly more frequently than expected, suggesting that the development of the two tumors was influenced by a common mechanism. In patients with asynchronous bilateral breast cancer there was a significantly longer interval between tumors if both were receptor-positive compared with concordant receptor-negative tumors and tumors with discordant receptor status. There was a significant discordance in the receptor status of asynchronous tumors when the histology also differed, indicating that the tumors in this group were likely to be separate primary tumors.
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PMID:Estrogen receptors in bilateral breast cancer. 338 9

The estrogen receptor (ER)-positive human breast cancer cell line T 47D exhibited genetic instability under cell culture conditions which maintained almost continuous exponential growth. This resulted in the spontaneous generation of three ER-positive sublines with a range of DNA ploidies and distinctive phenotypes. One of these sublines, T 47D-5, exhibited resistance to the growth-inhibitory effects of the synthetic nonsteroidal antiestrogen tamoxifen and the synthetic progestin ORG 2058, in marked contrast to "wild type" T 47D cells (designated T 47D-7 in this study). T 47D-5 cells were cloned by limiting dilution and 11 clonal cell lines were tested for sensitivity to tamoxifen. Although all clones of T 47D-5 were significantly less sensitive than T 47D-7 cells, a spectrum of sensitivities was observed. Three clones, T 47D-5-13, T 47D-5-21, and T 47D-5-23, were further characterized by measuring the concentrations of receptors for estrogen, progesterone, growth hormone, and epidermal growth factor and responses to estradiol, tamoxifen, and progestin, in terms of both induction of specific proteins and effects on cellular proliferation. Although the T 47D-5 subline and clone T 47D-5-23 were insensitive to both the growth-stimulatory effects of estradiol and the inhibitory effects of tamoxifen, this was not related to the concentration of ER or its ability to induce progesterone receptor. Estrogen receptor levels were similar in resistant and sensitive clones of T 47D-5 [70,000-81,000 sites/cell] and were 2.5-fold greater than in the sensitive T 47D-7 line [32,600 +/- 5,000 (SEM) sites/cell]. Northern blots showed no difference in the size of ER mRNA transcripts between sensitive and resistant clones. Estradiol treatment increased progesterone receptor (PR) levels in all cell lines but the magnitude and sensitivity of this response were unrelated to growth responses indicating a divergence in estrogenic control of cellular proliferation and specific protein synthesis within these clones. T 47D-5, T 47D-5-13, T 47D-5-21, and T 47D-5-23 were all insensitive to the growth-inhibitory effects of ORG 2058. The progestin was also unable to increase lactogenic and epidermal growth factor receptor concentrations in these four lines in contrast to the response in T 47D-7 cells. The insensitivity to progestin in the T 47D-5 subline and its three clonal cell lines could be accounted for, in part, by a 75-80% reduction in PR levels when compared with T 47D-7 cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Genetic instability and the development of steroid hormone insensitivity in cultured T 47D human breast cancer cells. 339 Aug 30

When human breast cancer-derived MCF-7 cells were maintained in low estrogen medium (phenol red-free), the cells adapted to grow without added estrogen, but growth could be inhibited by antiestrogen in the medium. Estrogen-stimulated progesterone receptor levels remained basal but could be stimulated by estradiol. Estrogen receptor content increased steadily during adaptation, which may model the increasing levels of estrogen receptor observed in breast cancer with increasing patient age. The mechanism of the adaptation to low estrogen medium is unclear; however, cell lines such as MCF-7 may need to be cultured in the presence of an estrogen such as phenol red in order to maintain a stable estrogen-sensitive phenotype. On the other hand, maintenance of estrogen-dependent cells in low estrogen media may convert them to dependence on factors which are not currently understood. This may ultimately increase their value as models of hormone action.
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PMID:Adaptation of estrogen-dependent MCF-7 cells to low estrogen (phenol red-free) culture. 343 56

Iododesethyl tamoxifen aziridine (I-Tam-Az), an analog of the estrogen receptor-affinity label tamoxifen aziridine (Tam-Az) in which the ethyl group has been replaced by an iodine, has been prepared by two routes: (a) metallation of a bromotriarylethylene system, followed by reaction with iodine, and aziridinylation, and (b) direct iodination of a trimethylstannyl triarylethylene system that is the immediate precursor of I-Tam-Az. The latter method can be used to prepare [125I]I-Tam-Az rapidly and in good yield, both at carrier-added and no-carrier-added levels; specific activities greater than 200 Ci/mmol have been obtained. In competitive radiometric binding assays with the estrogen receptor, I-Tam-Az has an apparent affinity of ca. 20%, equivalent to that of Tam-Az. It also undergoes rapid and selective time-dependent, irreversible binding to the estrogen receptor. [125I]I-Tam-Az reacts covalently with estrogen receptor in uterine cytosol preparations; its attachment is rapid and efficient, but somewhat less selective than that of Tam-Az. Estrogen receptor in intact MCF-7 human breast cancer cells can also be labeled with [125I]I-Tam-Az, and autoradiographic analysis of salt extracts of labeled nuclear estrogen receptor on SDS-polyacrylamide slab gels shows highly selective labeling of a 65K protein. [125I]I-Tam-Az is an efficient, selective affinity label for the estrogen receptor, available at high specific activity, and should be useful in studies on estrogen receptor structure, dynamics, and chromatin interactions.
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PMID:[125I]iododesethyl tamoxifen aziridine: synthesis and covalent labeling of the estrogen receptor with an iodine-labeled affinity label. 344 83


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