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1.
To better understand the prognostic relevance of change in steroid receptor status, during the clinical course of breast cancer, we analysed the variation of estrogen and progesterone receptor (ER, PgR) status in a series of 532 primary tumors and metachronous accessible recurrences in individual patients. A more consistent variation was observed in patients with a receptor-positive primary (ER(+) or PgR(+)) than in those with a receptor-negative tumor (ER(-) or PgR(-)). Forty-four percent of PgR(+) and 24% of ER(+) tumors became negative, whereas only 20% of ER(-) or PgR(-) became positive. The changes were independent of tumor stage and menopausal status. However, steroid receptor variation appeared to be related to the interval between the primary tumor and relapse. In fact, the changes from ER(+) to ER(-) were more frequent in patients with a disease-free survival of less than 1 year, whereas changes from ER(-) to ER(+) occurred more often in patients with a disease-free survival of more than 3 years. Moreover, we observed a decrease in the number of ER(+) tumors following hormone treatment and a decrease in ER(-) tumors following chemotherapy. However, such variations did not reach statistical significance. Irrespective of the type of adjuvant therapy, the presence of at least one receptor (in particular, PgR) in the metachronous lesion was correlated with a long median time to relapse and to death. Our results confirmed the predictive relevance of receptor status of the primary lesion on relapse and survival and suggest the predictive relevance of receptor status of the metachronous lesion on post-relapse survival.  相似文献   

2.
Estrogen and progestin receptor levels (ER and PgR) in tumors from 506 patients with primary breast cancer diagnosed in 1979, 1980, and 1981 were measured by a Scatchard plot analysis. At a median follow-up time of 3.5 years the prognostic value of the receptor levels was evaluated and compared with other tumor and patient characteristics. No relation was found between receptor levels and tumor, lymph node, metastasis (TNM) classification or location of the primary tumor. A significant positive rank correlation was observed between ER and PgR levels (rs = 0.57) and between ER level and age of the patients (rs = 0.39, P less than 0.001). The observed association between ER level and menopause status could not be maintained after correction for age. Independent prognostic factors for overall survival were tumor size (P = 0.002), the number of positive lymph nodes (P less than 0.001), age at primary surgery (P less than 0.001), the PgR level of the tumor (P less than 0.001), but not ER level. Independent prognostic factors for relapse were tumor size (P = 0.003), number of positive lymph nodes (P less than 0.001), age (P = 0.006), menopause status (P = 0.02), PgR level (P = 0.007), but not ER level. Finally, for death rate after relapse the following prognosticators were identified: size of the primary tumor (P = 0.03), number of positive lymph nodes (P = 0.03), age (P = 0.003), site of relapse (P less than 0.001), ER level (P = 0.02), and PgR level (P = 0.04). Patients with tumors containing low positive PgR levels (10 to 20 fmol/mg protein) had a slightly better prognosis than patients with PgR-negative tumors. It is concluded that the PgR level of the primary tumor is a better prognosticator than the ER level. The ER offered no additional ability for discriminating between low- and high-risk patients once PgR was included in the model. In contrast, PgR was capable of improving on the discriminating ability of ER. In addition, patients with tumors containing both PgR and ER showed the best prognosis. Therefore, it is recommended that ER and PgR should be assayed in all breast cancer biopsies.  相似文献   

3.
Estradiol receptor alone or estradiol and progesterone receptors (ER, PgR) have been measured in tumors from 307 women who were treated for primary breast adenocarcinoma. Patients received adjuvant therapy in relation to tumor stage independently of receptor status. Over a relatively short follow-up, more recurrences are recorded in patients with ER+ tumors, but at 7 years the same proportion of recurrences are registered in both groups of patients whose tumors were ER+ or ER-. Patients whose tumors were processed for both ER and PgR (148 cases) have now been evaluated after 5 years follow-up. Among 56 patients with PgR+ tumors 5 recurred, versus 22/92 in the PgR- group. 21/87 patients who had 1 to 4 invaded nodes at the time of surgery relapsed: 17/54 had PgR- tumors versus 4/33 PgR+. 6 recurrences were recorded in the 61 patients with negative nodes: 5 of them occurred in patients with PgR- tumors. In addition, recurrences observed in patients with negative receptor status occurred after a shorter disease-free interval. Analysis of the incidence of recurrences in relation to the combined ER/PgR status in patients who did not receive adjuvant therapy suggests that tumor PgR content is a more significant criterion than ER for long-term prognosis.  相似文献   

4.
The effects of two hormonal agents with different mechanisms of action, medroxyprogesterone acetate (MPA) and tamoxifen (TAM), on the tumor growth and hormone receptor status were evaluated in rat mammary tumors induced by 7,12-dimethylbenz[alpha]anthracene (DMBA). All estrogen receptor-positive (ER(+)) tumors became ER-negative (ER(-)), and 3 out of 4 progesterone receptor-negative (PgR(-)) and ER(+) tumors became PgR-positive (PgR(+)) after daily, oral administration of TAM for 2 weeks. In contrast, ER and PgR remained unchanged after daily administration of MPA for 2 to 4 weeks. All the ER(+) and PgR(-) tumors were transformed into PgR(+) after daily treatment with MPA for 2 weeks and then with TAM for another 2 weeks, but tumor regression was modest and none disappeared completely. In contrast, complete remission was achieved in all ER(+) tumors in the group treated with TAM for 2 weeks and then with MPA for another 2 weeks. The results suggest that the antitumor activity of the latter treatment regimen was significantly higher than that of the former. The possible mechanisms of antitumor activity of two hormonal agents are discussed.  相似文献   

5.
Estrogen and progesterone receptors as prognostic factors in breast cancer   总被引:1,自引:0,他引:1  
The relation between estrogen receptors (ER) and/or progesterone receptors (PgR) and some clinical factors such as tumor size, axillary node involvement, histological tumor grade, and disease-free interval (DFI) in 500 patients with operable (TNM stage I-III) breast cancer was studied. ER-positive (ER+) tumors were commoner in older patients, whereas PgR-positive (PgR+) tumors were similarly distributed within the age groups. The concentration of ER+ protein also increased with age in contrast to PgR+ protein concentration. However, receptor status was not associated with menopausal status independently of age. Axillary node involvement influenced neither ER nor PgR status, but there was a statistically significant relation between tumor size and positivity of ER or PgR. There was no association between histologic tumor grade and either steroid receptor phenotype. DFI was longer in patients with ER+ than those with ER- tumors, independently of axillary nodal status. The positivity of PgR in patients with ER+ tumors contributed to an even longer DFI, suggesting that the combination of ER/PgR is a better indicator of DFI than ER or PgR alone.  相似文献   

6.
This paper addresses the expression of the epidermal growth factor (EGF) gene by human breast tumor biopsy samples. Northern analysis was used to demonstrate the presence of an approximately 5-kilobase mRNA which specifically hybridized with radiolabeled human EGF complementary DNA in some human breast tumor biopsy samples. Quantitation of EGF mRNA in 60 human breast tumor biopsies using the RNase protection assay revealed that 83% of tumors contained detectable EGF mRNA. Estrogen receptor (ER) and progesterone receptor (PgR) mRNAs were similarly quantitated in the same samples. It was found that 89.4% of the ER mRNA-positive breast tumor biopsies had detectable EGF mRNA, whereas only 58.3% of the ER mRNA-negative tumors had detectable EGF mRNA. Furthermore, whereas 90.5% of the PgR mRNA-positive tumors contained EGF mRNA, only 60% of the PgR mRNA-negative tumors contained EGF mRNA. chi 2 analysis indicated that the increased percentage of tumors expressing EGF in the receptor-positive groups was statistically significant (P less than 0.01). It was also found that the mean relative level of EGF mRNA in those tumors which were ER and PgR negative [9.8 +/- 5.6 (SEM) relative units] was significantly lower than those tumors which were ER and PgR positive (40.5 +/- 6.4 relative units, P less than 0.05) or ER positive and PgR negative (68.4 +/- 19.9 relative units, P less than 0.005). These observations suggest that the EGF-expressing tumors probably arose originally from hormonally responsive cell types and that EGF expression in a large proportion of human breast tumors in vivo may also be hormonally responsive.  相似文献   

7.
The main objective of this study was to differentiate between lymph nodes infiltrated by estrogen receptor-positive (ER+) and estrogen receptor-negative (ER-) breast carcinoma. Lymph nodes were obtained from 40 postmenopausal cancer patients, 10 from each disease stage. Six patients from each group had estrogen receptor-positive (BCaER+) and four estrogen receptor-negative (BCaER-) tumors. Both tumor-containing (T) and uninvolved (N) lymph nodes from the same patient were examined by the following parameters: magnitude of lymph node nucleic acid hybridization with cDNA probes from breast cancer MCF-7ER+ and MCF-7ER- cells; and binding capacity of 3H-estradiol, 125I-EGF, and 125I-PDGF binding and protein kinase C activities of the lymph nodes. Concomitant with the appearance of transformed cells, several events occur: Tumor cells induce stimulation of mononuclear cells and macrophages and evoke T- and B-cell proliferation, leading to the synthesis of tumor cell membrane-associated antibodies. In estrogen receptor-positive (ER+) breast carcinoma, estrogens and host hormonal modulatory mechanisms stimulate production and release of epithelial growth (EGF) and platelet-derived growth factors (PDGF). These factors are characterized by protein kinase C activities. There is infiltration of tumor cells into the lymph node and infiltration of leukocytes into the tumor site. In the lymph node, tumor progression depends on tumor cell proliferation rate and metastatic aggressiveness. The experiments described in this study document the changes that occur in lymph nodes, with differences between nodes infiltrated with BCaER+ and BCaER- breast carcinomas. Hybridization of 32P-cDNA from MCF-7ER+ cells with cellular RNA from BCaER+ involved (T) lymph nodes is greater than with cellular RNA from uninvolved (N) lymph nodes. The magnitude of hybridization correlated (P less than 0.005) with the disease stage.  相似文献   

8.
To investigate the frequency of estrogen receptor ( ER ) gene mutation in metastatic or recurrent breast cancer, metastatic lymph nodes or recurrent breast cancer tissue from 35 patients with ER-positive primary tumors were screened for mutations in the hormone-binding domain of the ER gene by sequence analysis. Four missense mutations, Val316Ile, Gly344Val, Ala430Val and Gly494Val, were identified in these lesions. Second, to clarify whether there is any disparity in hormone receptor status between primary and metastatic or recurrent tumors, we immunohistochemically studied 117 specimens including the above 35 specimens obtained from metastatic or recurrent breast cancer patients using monoclonal anti-ER and progesterone receptor (PgR) antibodies. Although hormone receptor status, especially ER, was highly maintained through disease progression, negative change in PgR expression at relapse (33%) was identified more frequently than in metastatic lymph nodes (6.7%). Therefore, it was suggested that development of PgR-negative phenotype might correlate with disease progression in some breast cancer patients. These results suggest that ER mutations in metastatic or recurrent breast cancer may be more frequent than in primary lesions, irrespective of high maintenance of ER protein expression through disease progression.  相似文献   

9.
Simultaneous analyses of p(185/Her2) and pS2 protein expression in breast cancer is discussed to add information about prognosis and response to endocrine treatment. In a retrospective study, expression of p(185/Her2) and pS2 protein were detected by immunohistochemistry in paraffinembedded, formalin-fixed sections of 219 primary breast cancers. Median age was 56.6 years, median follow-up 168 months. Results were correlated with clinical parameters and steroid receptor status. ER was positive in 55%, PgR in 54% of the tumors. ER correlated inversely with tumor size, and with tumor grade. pS2 was detected in 54% of the tumors, but showed no correlations with other parameters. p(185/Her2) was present in 24% of the tumors and correlated positively with tumor size. pS2 and ER or PgR status correlated (p<0.001). In the sub-group of negative steroid receptors and positive pS2 a qualitative significant difference for p(185/Her2) expression was seen. ER, pS2 and p(185/Her2) status had no prognostic impact on disease-free or overall survival; PgR status correlated with clinical outcome.  相似文献   

10.
Background: To assess the immunohistochemical expression of estrogen receptor (ER), progesterone receptor(PgR) and human epidermal growth factor receptor-2 (HER2) neu receptor in breast cancer and their associationswith various clinicopathological characteristics. Materials and Methods: This is a retrospective analysis of womenwho presented with primary, unilateral breast cancer in the Department of Medical Oncology at Rajiv GandhiCancer Institute and Research Centre, Delhi, India during the period from January 2008 to December 2011. Datawere retrieved from the medical records of the hospital including both early and locally advanced cancer cases.ER, PgR and HER2neu expression in these patients was assessed and triple negative patients were identified.Associations of triple negative and non-triple negative groups with clinicopathological characteristics were alsoevaluated. Results: A total of 1,284 women (mean age 52.1 years, 41.9% premenopausal) were included in theanalysis. Hormone receptor positivity (ER and/or PgR) was seen in 63.4% patients, while 23.8% of tumors weretriple negative. Only 23.0% were HER2 positive. Around 10.0% of tumors were both ER and HER2 positive.ER and PgR positivity was significantly associated with negative HER2 status (p-value <0.0001). Younger age,premenopausal status, higher tumor grade, lymph node negativity, advanced cancer stage, and type of tumorwere strongly associated with triple negativity. Significantly, a smaller proportion of women had ductal carcinomain situ in the triple negative group compared with the non-triple negative group (35.6% versus 60.8%, p-value<0.01). Conclusions: The present analysis is one of the largest studies from India. The majority of the Indianbreast cancer patients seen in our hospital present with ER and PgR positive tumors. The triple negative patientstended to be younger, premenopausal, and were associated with higher tumor grades, negative lymph nodesstatus and lower frequency of ductal carcinoma in situ.  相似文献   

11.
The influence of various patient and disease-related parameters on survival (S) and disease-free survival (DFS) in 217 node positive primary breast cancer patients treated with surgery followed by adjuvant i.v. cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) was evaluated by univariate and multivariate analyses. Five year actuarial S and DFS were 73.3% and 54.8%, respectively. Univariate analysis revealed that patient age, number of involved axillary nodes and ER status had a significant impact on both S and DFS. PgR positive tumors had improved DFS but no S difference was observed. Menopausal status predicted S but not DFS. Primary tumor size and CMF-induced amenorrhea did not predict disease outcome. Multivariate analysis demonstrated that only degree of nodal involvement and PgR status had independent significant impact on prognosis. Both S and DFS are significantly influenced by the number of involved nodes, whereas improved DFS but not S was evident in patients with PgR positive tumors.  相似文献   

12.
An immunocytochemical assay (ICA) for the measurement of estrogen receptor (ER) and progesterone receptor (PgR) has been evaluated in 426 human primary breast carcinomas. For estrogen receptor determination ER ICA was used. PgR ICA was performed using the monoclonal antibody KD 68. Assay results for progesterone receptor immunocytochemistry were in agreement (P less than 0.0001) with those of biochemical determination in 74%. Progesterone receptor positivity determined with a semiquantified approach based on intensity and heterogeneity of immunocytochemical staining correlated significantly with biochemically determined progesterone receptor levels (P = 0.0001). Survival data showed a significantly better overall survival for patients with either ER ICA- or PgR ICA-positive carcinomas (ER ICA, P less than 0.00001; PgR ICA, P = 0.004). Patients with both negative ER ICA and PgR ICA showed a poorer prognosis than patients with only one negative receptor. In ER ICA- and PgR ICA-positive carcinomas a trend could be found that patients whose carcinomas contained high numbers of receptor-positive tumor cells had a better survival. This study demonstrates that ER ICA and PgR ICA are strong prognostic indicators and that the proportion of steroid hormone receptor-positive tumor cells seems to be of clinical importance.  相似文献   

13.
Two hundred consecutive postmenopausal women with operable breast cancer and metastatic axillary nodes were treated during the period January - December 1981 with adjuvant chemotherapy (CMF) or hormonal treatment (tamoxifen). The distribution of receptor status (estrogen or progesterone), number of axillary metastatic nodes (less than = 3 or greater than 3), surgical treatment and size of the primary tumor were homogeneous in both groups. Receptor status and number of axillary lymph nodes were correlated with adjuvant treatment efficacy. Ten-year disease-free survival (DFS) was higher in the TAM-treated (72%) than in the CMF-treated group (52%) (p less than 0.01). In patients with less than = 3 axillary metastatic nodes, those treated with TAM had a higher DFS rate than those treated with CMF (75% vs 59%, p less than 0.01). There was no difference in DFS between CMF-and TAM-treated groups within the greater than 3 metastatic lymph node patients. In ER + primary tumors, DFS was higher in the subset treated with TAM (62%) than with CMF (51%) (p less than 0.05), whereas no difference in DFS was observed in ER- patients between the two treatment groups. Considering the TAM group, DFS was better (p less than 0.01) for ER+ cases than for ER- cases only at 5 years of observation. In the CMF group, DFS was not influenced by ER status. PgR content did not affect DFS in either adjuvant treatment group.  相似文献   

14.
Levels of epidermal growth factor receptor (EGF-R) and insulin-like growth factor receptor (IGF-R) in breast cancer tissue were evaluated. The binding of growth factors was compared to the content of estrogen receptors (ER) and progesterone receptors (PgR). EGF-R correlated negatively to the ER and PgR (Kendall correlation, P less than 0.001), whereas the IGF-R correlated positively to ER and PgR (analysis of variance, P less than 0.001). In contrast, no correlation was found between EGF-R and IGF-R. IGF-R binding was higher in tumor tissues than in adjacent normal tissues (Wilcoxon rank test, P less than 0.001), whereas the EGF-R binding in normal tissue did not differ from that in cancer tissue. The degree of differentiation in ductal breast cancer correlated to EGF-R (chi 2 test, P = 0.018), but not to IGF-R. The bindings of both growth factors were the same in metastases and primary breast tumors. Our results show that EGF-R and IGF-R are present in normal breast tissue and breast cancer tissue. The growth factor receptors are related to steroid receptor content and their presence is associated with malignant transformation of breast cells and dedifferentiation of breast cancer.  相似文献   

15.
Cytosol levels of carcinoembryonic antigen (CEA), CA15-3, estrogen receptor (ER) and progesterone receptor (PgR) of 194- primary breast cancer tissues were measured. ER and PgR determined by enzyme immunoassay methods correlated inversely with Page's grades of histological atypia and mitotic rate. Cytosol CA15-3 correlated inversely with the grades of tubular and nuclear atypia and positively with the mitotic rate. CA15-3 correlated positively with ER and PgR. Cytosol CEA showed no correlation with the pathological grade or hormone receptor status. These results indicate that hormone receptor-positive breast cancers tend to have more differentiated morphology and slower growth rate than those without those receptors and that the cytosol CA15-3 level may reflect some of the intrinsic malignant potency, particularly the growth rate, of breast cancer. Cytosol CA15-3 as well as the hormone receptor status may have prognostic value for patients with breast cancer.  相似文献   

16.
Cytosol levels of carcinoembryonic antigen (CEA), CA15-3, estrogen receptor (ER) and progesterone receptor (PgR) of 194 primary breast cancer tissues were measured. ER and PgR determined by enzyme immunoassay methods correlated inversely with Page's grades of histological atypia and mitotic rate. Cytosol CA15-3 correlated inversely with the grades of tubular and nuclear atypia and positively with the mitotic rate. CA15-3 correlated positively with ER and PgR. Cytosol CEA showed no correlation with the pathological grade or hormone receptor status. These results indicate that hormone receptor-positive breast cancers tend to have more differentiated morphology and slower growth rate than those without those receptors and that the cytosol CA15-3 level may reflect some of the intrinsic malignant potency, particularly the growth rate, of breast cancer. Cytosol CA15-3 as well as the hormone receptor status may have prognostic value for patients with breast cancer.  相似文献   

17.
In a retrospective multicenter study to investigate the correlation between estrogen (ER) and/or progesterone receptors (PgR) in primary breast cancer with patient prognosis, 3118 patients with operable breast cancer (International Union Against Cancer Stages I, II, and III) were investigated from ten hospitals in Japan who underwent surgery from October 1972 to December 1982; 3089 were evaluable. The ER-positive and PgR-positive cancers were found in 56% and 34% of patients, respectively. The positivities decreased as the tumor size increased but were independent on lymph node metastasis. There were no significant differences in relapse-free survival (RFS) in relation to receptor status (median follow-up, 89 months [ER], 84 months [PgR]). However, in patients with four or more positive nodes, those with PgR-positive cancer had a longer RFS. The patients with ER-positive cancer survived significantly longer than ER-negative ones, with the greatest difference seen in those with four or more positive nodes. There was a significantly longer postrelapse survival (PRS) for patients with ER-positive cancer because of the different distribution of the major metastasis and better responses to first-line and subsequent treatments. Cox's multivariate analysis showed that overall survival but not PRS was affected by ER (and more weakly by PgR) because of the longer PRS in patients with ER-positive cancer.  相似文献   

18.
BACKGROUND AND OBJECTIVES: We investigated whether expression levels of c-erbB-2 and p53 proteins in breast cancer tissues differ in primary and metastatic lesions. METHODS: Immunohistochemical staining or sandwich enzyme immunoassay was used to determine expression levels of c-erbB-2 and p53 proteins in 42 breast cancer samples from 21 patients. Estrogen (ER) and progesterone receptors (PgR) were also measured by enzyme immunoassay in each case. All patients had undergone radical surgery for primary tumors and surgical resection of asynchronous metastatic lesions. Thirteen patients (62%) were premenopausal and 14 (67%) received postoperative adjuvant therapies. Median disease-free survival time was 26 months (range, 5-104). The resected metastatic lesions included 1 in the liver, 3 in the lung, and 3 in the supraclavicular lymph nodes. The remaining 14 were local skin lesions. RESULTS: There was no difference in the positivity rate of c-erbB-2 (38%: 8/21) and p53 (39%: 7/18) expression between the primary tumors and the recurrent lesions. In addition, no discordant c-erbB-2 or p53 expression was observed between the primary tumors and their respective metastatic lesions. Positivity rates for ER and PgR were 50% (10/20) and 60% (12/20) for the primary tumors, but only 25% (5/20) and 30% (6/20) for the recurrent lesions, respectively (P = 0. 19 for ER and P = 0.11 for PgR). CONCLUSIONS: c-erbB-2 and p53 expression levels in breast cancer cells were almost unchanged as the disease progressed and/or in response to adjuvant therapies, regardless of the hormone receptor status.  相似文献   

19.
Summary Estrogen (ER) and progesterone receptor (PgR) analyses have been performed in 884 primary, malignant human breast tumor biopsies. Receptor contents were evaluated with respect to age and menopausal status. The frequency of ER + tumors was found to be significantly higher in postmenopausal than in pre/perimenopausal women. Age rather than menopausal status was found to be associated with this difference. The significant association with age was found in the post- but not the pre/perimenopausal women.The frequency of PgR + tumors was found to be significantly lower in the postmenopausal than in the pre/perimenopausal women. Neither age nor menopausal status alone could account for this difference, which appears to be due to a compound effect of the two factors.The distribution of receptor profile patterns is described according to menopausal status. The patterns differ significantly in pre- and postmenopausal women. PgR dominates in the premenopausal tumor while ER dominates in the postmenopausal tumor. This difference is apparent within the subgroup of ER + PgR + patients as well.The current tenets for prediction of recurrent disease utilizing steroid hormone receptor determinations are discussed for the group of ER + PgR + patients.sponsored by The Danish Cancer Society  相似文献   

20.
Summary Estrogen (ER) and progesterone receptor (PgR) content of tumors were determined by both the dextrancoated charcoal (DCC) cytosol and immunocytochemical assays (ICA), and these hormone receptor results were compared to lymphocyte immunity against tumor antigen(s) for 52 breast carcinoma patients. Hormone receptor analysis by both methods demonstrated that 60% of the patients' tumors had ERs, while 44% were positive for PgRs. The ICA procedure was more sensitive than the cytosol technique for determining PgR content of the tumors. This increased sensitivity was not observed for ER by ICA. Patient age, tumor size, and nodal status were not related to the ER and PgR receptor status. A total of 21/52 (40%) of the patients had positive lymphocyte immunity against tumor antigen. This immunity was independent of patient age, tumor size, and nodal status. There was no significant relationship between lymphocytic immunity against tumor antigen and ER or PgR content of tumors, suggesting that patient lymphocyte immunity against tumor is independent of hormone receptor status. This is further evidence that lymphocyte immunity against tumor antigen status is an independent prognostic indicator that may be useful in the selection of a subset of node negative patients for adjuvant chemotherapy.  相似文献   

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