Estrogen receptor values in patients with benign breast disease.

Tissue specimens from 55 female patients with benign breast disease were assayed for estrogen receptor. Twenty-one of 55 patients (38%) had tumors which contained significant amounts of estrogen receptor (greater than 10 femtomoles/mg protein). Fibroadenomas possessed estrogen receptor more frequently than fibrocystic disease or other benign breast tumors. Estrogen receptor positivity did not correlate with laterality of the tumor; location or size of the largest nodule. Patients with estrogen receptor positive tumors had a mean age of 26.9 years compared to 36.4 years for patients with estrogen receptor negative tumors (p less than 0.01). Twenty of 46 (43%) premenopausal patients had benign tumors which were estrogen receptor positive compared to zero of 8 postmenopausal patients (p less than 0.05).     

The effect of estrogen usage on the subsequent hormone receptor status of primary breast cancer

In order to determine if prior use of exogenous estrogens was related to the estrogen receptor (ER) content of primary breast cancers, a retrospective analysis was performed from 536 patients with invasive breast cancer. The patient's age, menopausal status, oral contraceptive or estrogen replacement therapy usage, and the ER and progesterone receptor (PR) content of the breast cancer were recorded for all patients. Hormone usage in premenopausal and postmenopausal patients was compared to ER and PR levels in primary breast cancers using nonparametric testing. Complete information was available from 508 (193 premenopausal and 315 postmenopausal) patients. Breast cancers were ER positive in 72% of postmenopausal patients and 57% of premenopausal patients. The majority of patients received 'Some' form of hormone therapy (111 of 193 premenopausal patients and 233 of 315 postmenopausal patients). Significantly more estrogen receptors were detected in tumors from patients receiving 'some' estrogen therapy compared to 'never' users. Postmenopausal patients 'never receiving estrogen therapy had a lower rate of ER positive tumors (62%) compared to 'some' users (75% ²=4.99, p<0.05). The same relationship was seen for PR ('never' users 44% positive, 'some' users 58% positive, ²=5.19, p<0.05). We conclude that postmenopausal patients who received 'some' estrogen therapy are more likely to have breast cancers that are estrogen receptor and progesterone receptor positive.     

Localization of estrone sulfatase in human breast carcinomas

We generated anti-human El-STS monoclonal antibodies to localize estrone sulfatase (E1-STS) in human breast carcinomas. In particular, we examined the MCF-7 clone E3, ZR-75-1, MDA-MB 231, and MDA-MB-468 breast cancer cell lines and 25 breast carcinomas by either immunohistochemistry or Western blotting analysis. Simultaneously, we analyzed histological data, estrogen receptor (ER) status, progesterone receptor (PgR) status and epidermal growth factor receptor (EGFR) in breast tissue. All were surgical specimens from female patients. Nine of 25 carcinomas were obtained from premenopausal women, and 16 carcinomas were obtained from postmenopausal women. All cell lines demonstrated positive staining for E1-STS. Interestingly, fine granulated staining of E1-STS on the cell membrane was observed. In addition, Western blotting analysis detected a 65 kD protein with an E1-STS specific band in all breast cancer cell lines regardless of the presence or absence of E2. Twenty-two of 25 (88.0%) carcinomas showed positive staining for E1-STS, whereas negative staining was observed in the interstitial tissue surrounding tumors. In the premenopausal patients, 8 of 10 carcinomas (80.0%) showed positive staining for E1-STS, whereas 14 of 15 carcinomas (93.3%) revealed positive staining in the postmenopausal patients. The frequency of E1-STS expression was relatively higher in postmenopausal patients than in premenopausal patients but not statistically significant. The intensity of immunostaining for E1-STS depended upon the size of the tumor (NS). There was no correlation between E1-STS expression and other parameters. This evidence suggests E1-STS expression may be involved in the development of breast cancer. Further studies are necessary to clarify the relationship between E1-STS expression and prognostic factors. Immunoreactive E1-STS may be localized in cancer cells but not in surrounding tissues in breast cancer.     

乳腺癌绝经前后c-erbB-2、ER、PR的表达及与预后的相关性

 目的 探讨乳腺癌绝经前后c-erbB-2、ER、PR受体的表达差异及其与预后的相关性。 方法 回顾性分析432例乳腺癌的病理学资料,其中195例患者随访5年,c-erbB-2、ER、PR的表达采用免疫组化法检测。 结果 （1）绝经前组,c-erbB-2阳性患者的ER阳性率显著低于c-erbB-2阴性患者（P=0.003）;绝经后组,c-erbB-2阳性患者的ER、PR阳性率均显著低于c-erbB-2阴性患者（P＜0.001,P=0.005）。（2）多因素分析显示,绝经前组的独立预后因素为淋巴结转移、c-erbB-2,绝经后组的独立预后因素为淋巴结转移、c-erbB-2和ER。 结论 绝经前与绝经后乳腺癌c-erbB-2、ER、PR受体表达的临床意义有所不同。     

Plasma prolactin concentrations and risk of postmenopausal breast cancer

Prolactin is important in human breast development, and substantial laboratory and in vitro data suggest a role in mammary carcinogenesis. Therefore, we conducted a prospective case-control study nested within the Nurses' Health Study cohort to examine, in detail, the association between plasma prolactin concentrations and postmenopausal breast cancer by cancer invasiveness, estrogen receptor/progesterone receptor status, and other subject characteristics, including postmenopausal hormone use. Blood samples were collected from 1989 to 1990 and prolactin was measured by microparticle enzyme immunoassay. The analysis included 851 cases of postmenopausal breast cancer diagnosed after blood collection and before June 2000, in which there were one or two controls (n=1,275) matched on age, postmenopausal hormone use, fasting status, and time of day and month of blood collection. Prolactin was associated with a modestly increased risk of postmenopausal breast cancer [relative risk, top versus bottom quartile, 1.34; 95% confidence interval (CI), 1.02-1.76; P-trend = 0.01]. The association differed by estrogen receptor/progesterone receptor status (P-heterogeneity=0.03). The relative risk was 1.78 (95% CI, 1.28, 2.50; P-trend < 0.001) for estrogen receptor+/progesterone receptor+, 0.76 (95% CI, 0.43, 1.32; P-trend=0.28) for estrogen receptor-/progesterone receptor-, and 1.94 (95% CI, 0.99, 3.78; P-trend=0.12) for estrogen receptor+/progesterone receptor- breast cancers. Associations generally were similar for ductal and lobular carcinomas (P-heterogeneity=0.43) and by tumor size (P-heterogeneity=0.24). Among estrogen receptor+/progesterone receptor+ cancers, the association did not significantly differ by postmenopausal hormone use, years between blood draw and diagnosis, or after adjustment for estradiol (relative risk, 1.93; 95% CI, 1.16, 3.22; P-trend=0.01). Our prospective data suggest that plasma prolactin concentrations are associated with an increased risk of postmenopausal breast cancer, particularly for estrogen receptor+/progesterone receptor+ cancers, and independently of estradiol.     

Prognostic value of steroid hormone receptors: multivariate analysis of systemically untreated patients with node negative primary breast cancer

The value of estrogen and progesterone receptor (ER and PgR, respectively) determinations in predicting the recurrence-free survival (RFS) has been evaluated in a group of 807 node negative breast cancer patients. All of these patients are enrolled in the Danish Breast Cancer Cooperative Group (DBCG) 77-1a and 82-a protocols for low risk patients, and none of them have received systemic adjuvant therapy. At a median observation time of 50 months and in an evaluation of the total patient population as an entity, ER+ patients had only a marginally significant (P = 0.07) longer RFS than ER- patients while PgR+ patients experienced a significant advantage (P = 0.02). Among patients subgrouped according to menopausal status, both ER and PgR statuses were found to be significant prognostic factors for predicting RFS in the premenopausal women (less than 50 years) but not in peri- or postmenopausal women. Using Cox's multivariate analysis, nuclear pleomorphy was found to be the only significant prognostic variable, while the value of PgR status as a prognostic factor approached significance (P = 0.065). Although knowledge of ER status did not significantly improve distinction between patients with good and poor prognoses in the relatively small subgroup of premenopausal patients (n = 120) when PgR status was known, ER+PgR- patients have a lower risk of recurrence or death than ER-PgR- patients. Using a log-likelihood model, significant and distinct cut-off limits for the definition of receptor positivity were found for premenopausal patients: these were 5 fmol/mg cytosol protein for ER and 10 fmol/mg cytosol protein for PgR. These cut-off levels may reflect the ability of the ligand binding assay method used to discriminate between tissues with and without receptor proteins. Qualitative assessment of receptor status was as valuable as quantitative expression of receptor concentrations in predicting the RFS of the natural course of the disease among node negative premenopausal patients.     

Steroid receptors in a group of Brazilian breast cancer patients

Two hundred and forty-two primary breast cancers were assayed for estrogen receptors (ER). Of these, 202 were analyzed for progesterone receptors (PR) and 155 for glucocorticoid receptors (GR). ER was positive in 58% of the specimens; PR and GR were positive in 57%. A positive association was found between ER but not PR or GR frequency and age. Frequency of ER, PR, and GR positivity was approximately the same in premenopausal and postmenopausal women but ER content was much higher in postmenopausal women. About 70% of ER+ patients were also PR+ and GR+. Both frequency of PR positivity as well as average concentration, and frequency of GR positivity as well as average concentration were positively correlated with ER.     

Estradiol and Progesterone in Human Breast Cancer Cytosols and Their Relationship to Receptor Incidence

Plasma and breast cancer cytosol estradiol and progesterone levels were determined in pre and postmenopausal women and correlated with tumor estrogen and progesterone receptor incidence and content. There was no statistical correlation between plasma estradiol levels and estrogen or progesterone receptor incidence or content in premenopausal patients. Similarly, no correlation was apparent between plasma estradiol and progesterone levels, and tumor cytosol steroid concentration in either pre or postmenopausal women. In contrast to these observations, a significant inverse relationship developed between plasma progesterone levels and progesterone receptor incidence in premenopausal patients. An increase in tumor progesterone concentration in pre and postmenopausal patients was also significantly, and inversely related to receptor incidence. Our observations suggest that an increase in plasma progesterone and a decrease in tumor estrogen: progesterone ratio is significantly correlated with a decrease in estrogen and progesterone receptor incidence in pre- and postmenopausal patients.     

p29 protein in breast cancer: relation between estrogen and progesterone receptors

An immunoradiometric assay was used to determine the presence of p29 protein in 68 breast cancer cyTOSOLS. The p29 values ranged from 0 to 1123 U/mg, with a mean value of 127 +/- 28.7 U/mg. Using a cutoff point of 20 U/mg the frequency of p29 positive tumors was about 55%. A quantitative and qualitative relation was found between p29 and estrogen receptor (ER), but not between p29 and progesterone receptor (PR). Discordance between p29 and ER status was found in 13 out of 68 tumors. Both the frequency of p29 positive tumors and the p29 values were significantly higher in postmenopausal than in premenopausal women, in a similar way to ER but different from PR. There was no difference in p29 content between primary tumor and metastasis. We did not find any relation among p29 primary tumors content and axillary lymph nodes involvement or tumor size.     

Immunohistochemical labelling for prostate-specific antigen in breast carcinomas

Immunohistochemical detection of prostate-specific antigen (PSA) is an aid in determining the prostatic origin of metastatic cells. However, small amounts of PSA have also been found in non-prostatic tissues and tumors, for example in some breast carcinomas, by highly sensitive immunofluorometric methods, but also by immunohistochemistry. Our aim was to evaluate the prevalence and prognostic value of histologically confirmed PSA immunoreactivity in breast carcinoma. Sections of formalin-fixed, paraffin-embedded samples from 171 breast carcinomas were immunostained for PSA. The staining results were compared with the mitotic activity, tumor size, histological grade, steroid receptors and follow-up data. For analysis the material was divided into subgroups according to the patients' age (pre- and postmenopausal). PSA was found by immunohistochemistry in 54 (32%) breast carcinomas. In survival analysis of the whole patient material PSA positivity did not show prognostic value. Among premenopausal patients concomitant estrogen receptor and PSA-negativity proved to be associated with high risk of breast cancer death (RR 6.2), also after adjustment for tumor size, histological grade, and axillary lymph node status. Among postmenopausal patients PSA positivity was associated with progesterone receptor positivity and high differentiation but not with age, nodal status, or mitotic activity. PSA can be detected by immunohistochemistry in a considerable number of breast carcinomas. PSA immunoreactivity alone does not seem to have any value as general prognosticator of breast carcinoma patients. However, concomitant absence of PSA and estrogen receptors was an indicator of unfavourable prognosis among premenopausal patients.     

Survival of premenopausal breast carcinoma patients in relation to menstrual cycle timing of surgery and estrogen receptor/progesterone receptor status of the primary tumor

BACKGROUND: Premenopausal breast carcinoma patients who undergo tumor excision during the follicular phase of their menstrual cycle may have a significantly worse prognosis than those whose tumors are excised in other phases of the menstrual cycle. METHODS: Outcome was determined in a series of 112 premenopausal women with operable breast carcinoma in relation to the timing of surgery within the menstrual cycle and the estrogen receptor (ER) and progesterone receptor (PR) status of their primary tumors as determined by immunohistochemistry. RESULTS: Those patients with ER positive tumors who underwent surgery in the early and luteal phase of the cycle had a significantly better survival than women with ER negative tumors (chi-square test = 15.56; P < 0.001). This also was true for PR status (chi-square test = 18.21; P < 0.001). After follicular phase surgery, tumor receptor status had no effect on overall survival. Patients with the best prognosis had ER/PR positive tumors excised on Days 0-2 and 13-32 but even those women with ER or PR negative tumors removed during the luteal phase of their menstrual cycle fared better than patients whose tumors were removed during the follicular phase. CONCLUSIONS: There was a better survival rate for patients with both ER/PR positive and negative tumors treated during the luteal phase of the menstrual cycle. This could be the result of progesterone acting on the surrounding peritumoral normal tissue, thereby exerting a straitjacket effect and improving cohesion of the primary carcinoma. Unopposed estrogen in the follicular phase of the cycle may enable more tumor emboli to escape and successfully establish micrometastases.     

Hormonal receptor determination of 1,052 Chinese breast cancers

BACKGROUND AND OBJECTIVES: Hormonal receptors are important prognostic factors for breast cancer. The reported figures in the literature are mostly on Caucasians. This study analyzes the receptor profile of 1,052 Chinese patients. METHODS: The age of the patients ranged from 20-93 years; 48% were premenopausal and 52% postmenopausal. Estrogen receptor (ER) and progesterone receptor (PgR) were measured quantitatively by enzyme immunoassay (EIA) using the rat monoclonal antibody (ABBOTT ER-EIA). Specimens with values >15 fmol/mg were considered positive according to manufacturer's recommendation. RESULTS: ER was positive in 53% and 61.6% of the pre- and postmenopausal women respectively (P < 0.0075); PgR was positive in 51.5% and 46.2% respectively (P > 0.05). The mean values of ER were higher for postmenopausal women (P < 0.0001) but the values for PgR were similar between the two groups (P > 0.05). When the values were analyzed with respect to age, there was an increasing trend for ER. No such trend was noted for PgR. Subgroup analysis showed that there were more ER+PgR+ tumors among postmenopausal than among premenopausal women. Tumors with dubious receptor status (ER+PgR- or ER-PgR+) were more prevalent at perimenopausal age. CONCLUSIONS: Chinese patients have lower receptor values and positivity rates than those reported for Caucasians. Receptor-positive tumors tend to occur in postmenopausal women.     

Body size, physical activity, and breast cancer hormone receptor status: results from two case-control studies.

We evaluated whether our previous reports of increased postmenopausal breast cancer risk with higher body mass index (BMI) or of reduced premenopausal and postmenopausal breast cancer risk with higher physical activity levels varied according to the tumor's estrogen receptor (ER) and progesterone receptor (PR) status. Participants enrolled in either of two population-based case-control studies in Los Angeles County, California: one of premenopausal women (ages < or = 40 years), and one of postmenopausal women (ages 55-64 years). Case participants were diagnosed for the first time with in situ or invasive breast cancer from 7/1/83 through 12/31/88 (premenopausal women) or from 3/1/87 through 12/31/89 (postmenopausal women). Joint ER/PR status was collected for 424 premenopausal and 760 postmenopausal case participants. The analysis included 714 premenopausal and 1091 postmenopausal age-matched, race-matched (white or Hispanic), parity-matched (premenopausal women only), and residential neighborhood-matched control participants. Among the postmenopausal women, obesity was associated with an increased odds of ER+/PR+ breast cancer (odds ratio, 2.45 for women in the highest versus the lowest body mass index quartile; 95% confidence interval, 1.73-3.47). Body mass index was associated with neither ER-/PR- tumors among the postmenopausal women nor with any ER/PR subgroup among the premenopausal women. For both premenopausal and postmenopausal women, higher recreational physical activity levels (> or = 17.6 MET-hours/week versus no activity) were associated with a 30-60% reduction in risk of nearly all ER/PR subtypes, although the associations were generally of borderline statistical significance. Examining these potentially modifiable breast cancer risk factors by tumor ER and PR status may provide us with greater insight into breast cancer etiology and the mechanisms underlying the risk factor associations.     

Estrogen and progesterone receptors in human breast cancer. Correlation with histologic subtype and degree of differentiation

Microscopic review of 490 consecutive human breast biopsy and mastectomy specimens were correlated with estrogen and progesterone receptor content of the tissue, by subtype and degree of differentiation. Of the 4 grades of differentiation, the less differentiated Grade III and IV tumors showed significantly lower levels of estrogen and progesterone receptors in infiltrating ductal and lobular carcinoma (P less than 0.001). In contrast, patients with medullary carcinoma had the lowest tissue levels of estrogen and progesterone receptors with approximately 80% of the cases with less than 10 fmol/mg protein. Patients with mucinous carcinoma had the highest percentages of positive estrogen and progesterone receptor levels (75% and 87%, respectively). Sixty-three percent of the patients with Grade IV infiltrating ductal carcinoma were younger than 53 years of age (P less than 0.001). Patients younger than 53 years of age with Grade II and III infiltrating ductal carcinoma also had significantly lower levels of estrogen receptors, but not of progesterone receptors, than those patients older than 53 years of age (P less than 0.001). Nineteen of 20 "normal" breast tissue specimens were negative (less than 3 fmol/mg protein) for estrogen and progesterone receptors. About 50% of 17 tissue specimens from benign breast lesions (fibroadenoma, fibrocystic disease, sclerosing adenosis) showed positive estrogen (greater than 10 fmol/mg protein) or progesterone receptor values. In two patients with gynecomastia, no estrogen or progesterone receptors were detectable.     

Immunohistochemical Profile of Breast Cancer Patients at a Tertiary Care Hospital in New Delhi,India

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.     

Immunological quantitation of nuclear receptors in human breast cancer: relation to cytosolic estrogen and progesterone receptors

Nuclear estrogen receptors (ERn) can now be reliably analyzed using the monoclonal estrogen receptor enzyme immunoassay. In a consecutive series of 135 breast cancer biopsies, ERn as well as cytosolic estrogen receptor (ERc) and progesterone receptor (PgR) concentrations were determined to evaluate whether ERn assays provide additional valuable information for the clinical management of the disease. Furthermore, by performing analyses on this relatively large number of patients, we sought explanations for the occurrence of the receptor profiles of ERc negative PgR positive and ERc positive PgR negative, which are found in a significant proportion of tumor biopsies. Eight-four % of all tumors are classified as ERn positive (greater than or equal to 10 fmol/mg nuclear extract protein) using the monoclonal assay technique. Two trends are evident: ERc positivity was found to be associated with ERn positivity (greater than or equal to 10 fmol/mg cytosol protein) in 98% of the cases investigated; and PgR positivity (greater than or equal to 10 fmol/mg cytosol protein) was found to be associated with ERn positivity in 95% of the cases investigated. However, a major proportion (approximately 28%) of ERn positive tumors are either ERc negative or PgR negative. The pattern of ERc negative ERn positive occurs almost exclusively among younger women, most of whom also had detectable amounts of PgR in their tumor tissues, while the pattern of ERn positive PgR negative occurs primarily among older women. ERn concentration was found to be significantly correlated to the concentration of both PgR and ERc. While the correlation between ERn and PgR was found to be strongest among women younger than 50 years of age, the correlation between ERn and ERc was strongest among women older than 50 years. Young women were found to have a significantly higher proportion of total tissue estrogen receptor present as ERn than older women (27 versus 14%). The information obtained by performing ERn analyses concurrently with or in place of ERc and PgR analyses does not appear to be valuable for the clinical management of the disease. However, this new method for determination of ERn is a significant advance in receptor technology that permits reevaluation of established enigmas concerning the biology and natural history of breast cancer.     

Immunohistochemical labelling for prostate–specific antigen in breast carcinomas

Immunohistochemical detection of prostate–specific antigen (PSA) is an aid in determining the prostatic origin of metastatic cells. However, small amounts of PSA have also been found in non–prostatic tissues and tumors, for example in some breast carcinomas, by highly sensitive immunofluorometric methods, but also by immunohistochemistry. Our aim was to evaluate the prevalence and prognostic value of histologically confirmed PSA immunoreactivity in breast carcinoma.Sections of formalin–fixed, paraffin–embedded samples from 171 breast carcinomas were immunostained for PSA. The staining results were compared with the mitotic activity, tumor size, histological grade, steroid receptors and follow–up data. For analysis the material was divided into subgroups according to the patients' age (pre- and postmenopausal). PSA was found by immunohistochemistry in 54 (32) breast carcinomas. In survival analysis of the whole patient material PSA positivity did not show prognostic value. Among premenopausal patients concomitant estrogen receptor and PSA–negativity proved to be associated with high risk of breast cancer death (RR 6.2), also after adjustment for tumor size, histological grade, and axillary lymph node status. Among postmenopausal patients PSA positivity was associated with progesterone receptor positivity and high differentiation but not with age, nodal status, or mitotic activity. PSA can be detected by immunohistochemistry in a considerable number of breast carcinomas. PSA immunoreactivity alone does not seem to have any value as general prognosticator of breast carcinoma patients. However, concomitant absence of PSA and estrogen receptors was an indicator of unfavourable prognosis among premenopausal patients.     

Female sex steroid receptor status in primary and metastatic breast carcinoma and its relationship to serum steroid peptide hormone levels

In order to obtain more information on the interrelationships between cytosol estrogen (ER) and progestin (PR) receptors in breast carcinoma, and their distribution according to age, menopausal status and endocrine parameters of the patients, these receptors were measured in 605 primary and 150 metastatic lesions, and correlated with serum levels of estradiol, progesterone, FSH, LH and prolactin in some of these patients. Measurable estrogen receptor (> 3 fmol/mg cytosol protein) was found in 78.0% and progestin receptor (> 10 fmol/mg cytosol protein) in 60.5% of all the samples studied. The receptors were simultaneously present in 57.2%, estrogen receptor only in 20.8%, progestin receptor only in 3.3%, while both receptors were absent in 18.7% of the whole material. In samples from 253 premenopausal patients, measurable ER was found less frequently (71.1% of cases) and its concentration was lower (39.9 ± 5.1 fmol/mg cytosol protein, mean ± SEM) than in 502 postmenopausal patients (82%; 148.2 ± 11.6 fmol/mg). The frequencies of ER-positive samples and ER concentration were rather similar in primary and metastatic lesions, whereas PR was more often present (64 versus 47%) and its concentrations significantly higher (151.2 ± 12.5 versus 102.6 ± 21.1 fmol/mg) in primary than in metastatic tumors. When present simultaneously, there was a significant correlation between ER and PR concentrations in both primary and metastatic lesions independent of the menopausal status of the patient. ER concentration correlated significantly with age in both pre- and postmenopausal patients, while PR concentration correlated with age only in postmenopausal patients. The group with the highest ER values (above 100 fmol/mg cytosol protein) had a significantly lower serum estradiol concentration that the other patients. Serum estradiol values had a significantly positive correlation with cytosol PR content in the samples with a measurable PR. Serum progesterone, FSH, LH and prolactin did not correlate with tumor ER or PR concentrations. We conclude that concomitant assays of ER and PR from a breast carcinoma specimen provide a correct picture of the endocrine characteristics of the tumor independently of the serum concentrations of estradiol, progesterone, FSH, LH and prolactin.     

Progesterone receptors and human breast cancer

Estrogen receptor protein is known to be an important prognostic factor for patients with breast cancer. The presence of estrogen receptor correlates with response to endocrine therapy in patients with metastatic disease and is associated with prolonged disease-free and overall survival in patients with primary disease. But the correlation between estrogen receptor positivity and endocrine dependence is not perfect. Approximately 40% of estrogen receptor positive tumors fail to regress with endocrine therapy. It has been hypothesized that another protein, progesterone receptor, may be a more effective marker of endocrine responsiveness since progesterone receptor is the end product of estrogen action. We have examined the relationship between progesterone receptor and response of advanced breast cancer tumors to hormonal manipulations. Promising retrospective results indicate the need for new, prospective clinical trials to further define the prognostic value of progesterone receptor for these tumors. We have also analyzed the disease-free intervals of patients with primary disease and found that progesterone receptor was more important than estrogen receptor for predicting time to recurrence. We suggest that both estrogen receptor and progesterone receptor be routinely measured in all breast cancer tumors, and that the results of these assays will help the physician individualize therapy for breast cancer patients.     

Effect of interferons on hormone-receptor levels of endometrial cancer-cells

Endometrial cancer is a hormone sensitive tumor. Hormone receptor positive tumors respond better to progestins than hormone receptor negative tumors. Interferon has been shown to increase the hormone receptor level of melanocytes, breast and endometrial cancer. We have previously shown that interferons enhance the progesterone receptor level of AE-7 endometrial cancer cell line, which has a considerably high baseline level of progesterone receptors (201+/-19.7 fmole/mg of proteins). In this study the effect of interferons of two other endometrial cancer cell lines (HEC-1A and HEC-1B), with a low baseline level of estrogen and progesterone receptor levels (25+/-7-32+/-8 fmole/mg of proteins), was studied. Interferons have shown to possess similar cytostatic activity in the endometrial cancer cells studied, regardless of their hormone receptor status. However, hormone receptor levels in cells with low baseline hormone receptor levels were not significantly affected by the four interferons studied.