Estrogen Values Research Articles

The Prognostic Value of Estrogen and Progesterone Receptors in Female Breast Cancer. A Single Center Study

In the period from September 1980 to December 1987, our laboratory measured estrogen (ER) and progesterone receptor (PgR) levels in 960 patients with primary breast cancer. At presentation, 918 of these had no distant metastases. ER as well as PgR were considered positive at values above 10 fmol/mg cytosol protein. All the patients included had been operated on at one of two participating hospitals in the country of North Jutland, and all patients had been checked up in a uniform way at one oncological out-patient department. By applying test for interaction, the PgR was found to be dependent on nodal status. Separate multivariate analyses were carried out for node positive and node negative patients. By this method, size of tumor, histologic grading, and age turned out to be independent prognostic factors for the node negative patients. Independent prognostic parameters for the node positive patients were histologic grading, PgR and postoperative x-ray therapy. The results support the theory that PgR is a better predictor of disease-free survival than ER.

Predictive value of tumor estrogen and progesterone receptor levels in postmenopausal women with advanced breast cancer treated with toremifene

The predictive value of estrogen receptor (ER) concentrations was evaluated in a group of 113 postmenopausal patients with estrogen-receptor-positive (ER greater than 7 fmol/mg protein) advanced breast cancer. In 103 patients, tumors were also sampled for progesterone receptor (PgR) determination. All patients were treated with toremifene, a novel antiestrogen, 60 mg daily. The median ER in 51 responders was 78 fmol/mg protein, and in 62 nonresponders, 51 fmol/mg protein; the median PgR levels were 40 and 37 fmol/mg protein, respectively. The response rate in patients with ER less than 50 fmol/mg protein was 38%, and 51% in the group with ER greater than 50 fmol/mg protein (not significant [NS]). The response rate in patients with PgR less than 10 fmol/mg protein was 42%, and in patients with greater than 10 fmol/mg protein, 44%. The duration of response in patients with ER greater than 50 fmol/mg protein was significantly longer than with lower ER levels (P = 0.002). PgR was not associated with the duration of response. In Cox's multiple regression analysis, ER was an independent prognostic factor (P = 0.005) for response duration. Thus, the ER concentration of tumor tissue predicts the duration of response but not the response rate to toremifene in patients with advanced breast cancer. The PgR status does not predict the response rate or the duration of response.

A dose-comparative endocrine-clinical study of leuprorelin in premenopausal breast cancer patients

Twelve premenopausal patients with advanced breast cancer were randomised to receive 3.75 or 7.5 mg of a slow release formulation of the luteinising hormone releasing hormone agonist leuprorelin once every 4 weeks. All patients were oestrogen receptor positive or unknown. Serum levels of gonadotrophins and oestrogens were suppressed markedly by both doses. All oestrogen values during treatment were within the postmenopausal range except for a single oestradiol level (274 pmol l-1) in one patient on the lower dose. There was no other indication that this lower dose was less effective as an oestrogen suppressant. There were two objective responders to the 3.75 mg dose and three to the 7.5 mg dose. Toxicity was confined almost entirely to hot flushes which occurred in 11/12 patients. We conclude that the slow release formulation of leuprorelin is effective in breast cancer treatment and that there is no major detriment to the use of the 3.75 rather than 7.5 mg dose.

Estrogen and progesterone receptor content of endometrial carcinomas: Comparison of total tissue versus cancer component analysis

Estrogen (ER) and progesterone (PgR) receptor values in 105 endometrial carcinomas were compared using immunocytochemical and standard biochemical techniques. Peroxidase-antiperoxidase staining for location of anti-ER (H222) and anti-PgR (JZB39) primary antibodies was used to generate a semiquantitative (HSCORE) assessment of receptor content in tissue components and the total specimen. Both total HSCORE and cancer component HSCORE correlated with log biochemical assay values for ER and PgR. Biochemical assay values, total HSCORE, and cancer component HSCORES all demonstrated internal correlations between ER and PgR levels. Correlation was somewhat closer for cancer component HSCORE values of ER and PgR than the values for total tissue HSCORE. When receptor content was analyzed by histologic grade, all three estimates of receptor status demonstrated a decreasing proportion of ER and PgR positive lesions with decreasing histologic differentiation; however, the proportion of receptor negative lesions in grade 3 lesions was much higher when using total HSCORE or cancer component HSCORE than when using biochemical assay values ( P < 0.005). Immunocytochemical techniques for localization of ER and PgR in endometrial carcinoma specimens may allow a more focused evaluation of the receptor content in the malignant elements than standard biochemical techniques.

Comparison of sex steroid receptor determinations in human breast cancer by enzyme immunoassay and radioligand binding

Most investigators comparing ligand-binding procedures for quantifying estrogen and progestin receptors in human breast cancer with procedures employing monoclonal antibody-based methods have utilized an inappropriate variety of reaction conditions, including the elimination of sodium molybdate in the steroid-binding assays. We studied 197 biopsies of human breast cancer, comparing the results of simultaneous measurements of both estrogen and progestin receptors in identical cytosols by enzyme immunoassay and by radioligand binding using the commercially available kits developed by Abbott Laboratories and by DuPont/NEN Products, respectively. Regression analyses comparing the results from the two procedures indicated a linear relationship, with correlation coefficients ranging from 0.79 to 0.93 for both types of receptors over a wide range of data. Using the widely established cutoff value of 10 fmol/mg of cytosol protein for the ligand-binding method, and calculating sensitivity and specificity limits according to McNeil et al. (1975), an equivalent cutoff value of 15 fmol/mg of cytosol protein was determined for the enzyme immunoassay of these receptors. Endocrine status of the patient did not appear to alter the cutoff values of either estrogen or progestin receptors when determined by enzyme immunoassay. We recommend that these cutoff values be considered until the results of clinical correlations are completed.

Estrogen and Progesterone Receptor Analyses in More Than 4000 Human Breast Cancer Samples: A Study with Special Reference to Age at diagnosis and stability of analyses

Estrogen (ER) and progesterone receptors (PgR) were measured in the same laboratory in more than 4,000 breast cancer biopsy samples obtained from 15 different hospitals during ten years. ER was measured with isoelectric focusing and PgR with the dextran-coated charcoal method and Scatchard analysis. The distribution pattern for both ER and PgR was during this time period and for the different hospitals rather similar indicating a good stability of the analytical methods. ER concentration was positively correlated with patient age, with a higher percentage of positive samples and higher concentrations in patients greater than or equal to 50 years of age compared with patients less than 50 years. PgR concentration increased with age for patients under 50 years, but a considerable reduction of PgR concentration and of the proportion of positive samples was seen in patients between 50 and 59 years of age. Above this age the PgR concentration again increased with increasing age. The PgR/ER ratio and the proportion of ER- PgR+ samples were higher in patients under 50 years compared to older patients. ER and PgR values decreased during tamoxifen treatment, during pregnancy and after preoperative radiotherapy. Wet weight, DNA and protein were compared as reference parameters for the expression of ER and PgR concentrations. Strong correlations were obtained suggesting that similar information can be obtained with either of these reference parameters.

Prognostic value of estrogen and progesterone receptors in operable breast cancer

Prognostic value of estrogen and progesterone receptors in operable breast cancer

Prognostic value of estrogen and progesterone receptors in primary infiltrating ductal breast cancer: A sequential multivariate analysis of 1262 patients

Nine prognostic variables were evaluated for their significance in predicting the overall survival (OS), the length of disease-free survival (DFS) and the length of metastasis-free survival (MFS) of 1262 patients with primary breast cancer. The variables studied were: UICC clinical stage; menopausal status; histologic grade; number of involved nodes; anatomic tumor size; estrogen and progesterone receptors; local and adjuvant therapies. Three sequential multivariate analyses, at 2, 5 and 10 years, using the Cox proportional hazard regression model, were carried out to identify those variables most highly related to the criteria studied (overall, disease-free, metastasis-free survivals) and especially to fully evaluate the effects of hormonal receptors on prognosis and their stability over time. Our results showed that number of involved nodes and histologic grade were the most significant prognostic factors for all periods of time and whatever the criterion studied; ER had no predictive value while PR was an independent prognostic factor for metastasis-free survival at 2 years ( P = 0.01) and 5 years ( P = 0.02) but lost its significance at 10 years ( P = 0.06). In the subgroup of 261 patients who received prolonged post-operative adjuvant chemotherapies, PR was the main prognostic factor for MFS at 2 years ( P = 0.03) and the second at 5 years ( P = 0.05) just after number of involved nodes. In the 1001 patients who did not receive prolonged post-operative adjuvant chemotherapies ER was significant for MFS at 5 and 10 years. The present data urge the need for a periodic redefinition of prognostic factors in primary breast cancer.

The role of endogenous estrogens in the maturation process of the bovine placenta

The plasma estrogen and progesterone concentrations of 19 pregnant cows (average duration of pregnancy 266.0 ± 2.3 d at the start of the study) were determined daily from Day 6 pre partum to Day 1 post partum. Parturition was induced in all cows by administration of 10 mg i.m. flumethasone. Values were centered around the delivery date (Day 0) following either induced normal calving (n = 3) or surgical delivery (n = 16). In animals showing spontaneous expulsion of the fetal membranes (Group 1, n = 6) the average total estrogen concentration increased significantly from Day 6 until Day 1 before parturition (1329.2 ± 317.9 to 3719.8 ± 951.2 pg/ml in total estrogens). A marked decrease was observed on Day 1 post partum (459.4 ± 344.2 pg/ml). In comparison with Group 1, animals showing either a delayed or partial expulsion of the fetal membranes, or in which the placenta could be withdrawn 16 h after calving (Group 2, n = 5), had consistently lower total estrogen concentrations between Day 6 (595.4 ± 174.8 pg/ml) and Day 1 (1884.3 ± 565.1 pg/ml) before parturition. The estrogen values of the cows with retained placenta (Group 3, n = 8) from Days 6 to 0 pre partum were significantly lower than those of Group 2. Total estrogen concentrations of the three groups 1 d post partum did not differ significantly. It is generally recognized that estrogens play an important role in the maturation process of the placentomes. Our investigation demonstrates that not only is the magnitude of the prepartum rise in estrogens of great influence of the maturation process but the duration of this rise is likewise important. These two factors are vital for a normal expulsion of the fetal membranes.

Prognostic value of estrogen and progesterone receptors in operable breast cancer. Results of a univariate and multivariate analysis.

From October 1977 to December 1983, estrogen receptor (ER) and progesterone receptor (PR) levels were measured in 645 tumors from women with primary, unilateral, nonmetastatic breast cancer. All of them were treated surgically. Some received adjuvant radiotherapy, adjuvant chemotherapy, or adjuvant hormonotherapy. A level of greater than 5 fmol/mg cytosolic protein was considered as positive for both ER and PR. Unifactorial analysis, using Kaplan and Meier estimates and the log-rank test, revealed that disease-free survival (DFS) and overall survival (SV) were both strongly related to age, tumor size, nodal status, nodal effraction, histopathologic grading (SBR), ER, and PR. Menopausal status and number of intramammary tumor foci were not significant. Multifactorial analysis, using Cox's model, revealed a strong relationship between SV and age (poor prognosis [pp]: less than or equal to 37 years old), menopausal status (pp: postmenopausal) tumor size, nodal status (pp: N+ greater than 3), nodal effraction, ER (pp: less than or equal to 5 fmol/mg), histopathologic grading (pp: SBR = 3), and PR (pp: less than or equal to 5 fmol/mg). Similarly, multifactorial analysis revealed a strong correlation between DFS and age, tumor size, nodal status, nodal effraction, histopathologic grading, and PR. A prognostic score taking into account these prognostic factors was calculated for DFS and SV. Analysis of this score allowed us to divide our patients into four significantly different (P less than 0.0001) groups with high, intermediate, and low risk of relapse. Our procedure was then validated using the sample test technique. These results show that both ER and PR have their own prognostic weight and should be considered, among other classic prognostic factors, when adjuvant therapies are indicated after surgical treatment of breast cancer.

Physiological mechanisms associated with ovulation prediction using the CUE Ovulation Predictor.

It has been shown that monitoring of salivary electrical resistance (SR) enables prediction of ovulation several days in advance, since a peak in SR is seen 5-6 days before the LH peak. This paper explores physiological mechanisms that may account for this change. The pathway whereby oestrogen stimulates aldosterone (ALDO) secretion acting through the renin-angiotensin system was considered. It is shown that this mechanism would only result in increasing SR as oestrogen values rise during the follicular phase and therefore is not an explanation of the SR peak and declining SR 5-6 days before the LH peak. The reported trend of sodium in milk of ovulating women parallels that of SR. It is shown that these changes are most likely to be due to a similar change in aldosterone levels. A possible role for adrenocorticotrophic hormone (ACTH) in causing the changes in aldosterone is discussed and supported with data from other independent studies as well as with preliminary data obtained from two normally ovulating subjects. Peaks in ACTH, ALDO and SR were coincidental and occurred 6 days before the LH peak. The temporal relationship observed among these variables suggest that ACTH, by affecting ALDO, modifies salivary electrolytes and hence SR.

The prognostic value and relationships of patient characteristics, estrogen and progestin receptors, and site of relapse in primary breast cancer.

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.

Changes in estrogen and progesterone receptor content of primary breast carcinoma during the menstrual cycle.

This study was undertaken to determine if hormone receptor activity in breast cancers changes during different phases of the menstrual cycle. Estrogen (ER) and progesterone (PgR) receptors in seventy-eight primary breast carcinomas from premenopausal women were compared with the phase of the menstrual cycle at the time of biopsy. The frequency of ER positivity did not change, but PgR positivity became significantly higher after the early follicular phase. An increase in mean ER and PgR concentration was found (p less than .05) in the late luteal phase. The results indicate that tumor ER and PgR values change during the menstrual cycle, probably in response to endogenous hormonal fluctuations, and this may account for some vicissitudes in establishing hormone dependence.

GROWTH HORMONE AND PROLACTIN SECRETION AFTER GROWTH HORMONE‐RELEASING HORMONE ADMINISTRATION, IN ANOREXIA NERVOSA PATIENTS, NORMAL CONTROLS AND TAMOXIFEN‐PRETREATED VOLUNTEERS

Anorexia nervosa is associated with several abnormalities in GH secretion elicited by different stimuli. To investigate the precise mechanism of this alteration, GHRH was administered to 14 women: a group of eight anorexia nervosa patients in the acute phase of their illness and a control group of six age-matched volunteers. As patients with anorexia nervosa have chronic low oestrogen values, the volunteer women of the control group underwent a second GHRH test after pretreatment with the oestrogen receptor blocker tamoxifen. GHRH 1-29 (1 microgram/kg i.v.) induced a GH peak (mean +/- SEM) of 28.2 +/- 5.1 ng/ml (GH ng/ml x 2 = mU/l) at 30 min in the anorectic patients. This value was no different from the GHRH-stimulated GH peak in the control women (28.1 +/- 10.0 ng/ml). Tamoxifen pretreated women had a GH peak after GHRH of 35.6 +/- 9.7 ng/ml, not significant versus control test. Compared with the control group, oestrogen levels were significantly lower in anorectic patients and higher in tamoxifen-treated women. GHRH administration induced a small PRL peak at 15 min that was similar in the three groups tested. After this 15 min peak, PRL in both anorexic and tamoxifen-treated women returned toward basal values steadily. However, in untreated control women a second PRL peak was evident at 60 min. In conclusion, GHRH-induced GH secretion in anorexia nervosa patients was similar to that in control subjects and in controls under oestrogen receptor blockade.

Estramustine binding site in human breast cancer biopsy samples. Its relation to estrogen and progesterone receptor levels, age and menopausal status

Estramustine is a cytotoxic metabolite of estramustine phosphate (Estracyt ®), which is used in the treatment of prostatic carcinoma. An estramustine binding site (EMBS) at p H 4.8–4.9 was demonstrated in 74 of 306 (24%) breast cancer biopsy samples using isoelectric focusing in polyacrylamide gels. The presence of EMBS was significantly ( P < 0.001) correlated with negative or low estrogen and progesterone receptor values. EMBS positivity was found in 31% of the samples from pre- and perimenopausal patients and in 22% of the samples from postmenopausals. If patients were instead divided into different age groups, EMBS positivity was most frequent in samples from patients between 50 and 59 years of age (42%). With increasing age the percentage of EMBS positivity fell successively. For patients under 50 years, no difference with respect to EMBS positivity between age groups could be demonstrated. The possible value of EMBS determinations in breast cancer tissue specimens for the selection of those patients that will respond to Estracyt ® therapy should be evaluated.

Establishment and maintenance of pregnancy after embryo transfer in ovariectomized mares treated with progesterone.

Pregnancy was established and maintained after embryo transfer in 3 ovariectomized mares treated with progesterone only. Four ovariectomized mares were used as recipients, and 7 transfers were performed. Progesterone in oil, 300 mg i.m. daily, was given starting 5 days before transfer of a 7-day embryo. If the mare was pregnant at 20 days, progesterone treatment was continued to 100 days of gestation. The 3 pregnant mares carried to term and delivered live foals with normal parturition, lactation and maternal behaviour. No differences were seen between pregnant and non-pregnant ovariectomized mares in jugular plasma concentrations of oestrogen, LH or FSH from day of transfer (Day 7) to Day 20. Pregnant ovariectomized mares showed a rise in LH, reflecting production of horse CG, starting at Day 36. Oestrogen values remained low until Day 50.

Mating patterns in the golden lion tamarin (Leontopithecus rosalia): continuous receptivity and concealed estrus.

Sociosexual behavior was monitored on a daily basis for 3 months in 5 pairs of golden lion tamarins (Leontopithecus rosalia). Urine samples were collected daily from each female and urinary estrogen cycles were determined by radioimmunoassay. Mounts and copulations were observed during all phases of the estrogen cycle. Peaks or regular cycles in sexual behavior were not documented. There were no significant changes in affiliative behavior by females or males that were associated with changes in urinary estrogen values. A negative relationship between pair bond duration and frequency of sexual interactions was observed: newly established pairs exhibited 2-6 times more frequent sexual behavior than a long-established pair. The lack of a conspicuous sexual signal in female golden lion tamarins may be related to a pattern of continuous sexual receptivity. Both reproductive patterns, concealed estrus and continuous receptivity, are explicable in relation to either monogamous or polyandrous mating systems.

Preovulatory serum gonadotropin levels in hMG stimulated menstrual cycles in pregnant and nonpregnant patients

In a group of patients undergoing in vitro fertilization, 10 pregnant and 10 nonpregnant, cycles were analysed in retrospect in relation to gonadotropin and steroid hormones. All patients were similar in terms of age, body surface area and initial stimulation protocol. The increase in follicles stimulating hormone (FSH) was significantly higher in the pregnant group through cycle day 8 as compared with cycle day 3 before stimulation. A significant increase in the nonpregnant group was never detectable; the mean FSH levels rather decreased to the baseline value during stimulation after a slight nonsignificant increase. The levels of luteinizing hormone (LH) decreased significantly in pregnant and nonpregnant patients during stimulation. No significant difference in the FSH/LH ratio between the pregnant and nonpregnant group was encountered. Although the mean serum estrogen in the follicular phase and the serum estrogen and progesteron values in the luteal phase were higher in the pregnant patients, no statistically significant difference between groups could be demonstrated, until luteal day 11. It is believed from this study, that a 15-20% increase in serum FSH levels over baseline during the early and mid follicular phase is required for adequate follicular development and steroidogenesis. The determination of serum gonadotropins in the follicular phase in patients who failed to conceive, might reveal differences, which can account for failures in hMG induced cycles.

Urinary gonadotropin and estrogen excretion during the postpartum estrus, conception, and pregnancy in the cotton-top tamarin (Saguinus oedipus oedipus).

Hormonal profiles during postpartum estrus, time of conception, and pregnancy were determined in urine samples from six cotton-top tamarins (Saguinus oedipus oedipus). Noninvasive collection techniques permitted daily sampling throughout lactation and pregnancy. Urinary estrone (E1), estradiol (E2), and both bioactive and immunoreactive luteinizing hormone/chorionic gonadotropin (LH/CG) measures revealed an interval of 19 ± 2.07 (S E M) days between parturition and the postpartum ovulatory LH peak. An increase in both E1 and E2 was seen prior to the LH peak; however, E1 and E2 continued to increase to their highest concentrations after the LH peak. Since postpartum ovulations resulted in pregnancy, neither postpartum estrus nor conception was suppressed by lactation. The length of gestation (measured from the LH peak to parturition) was 183.7 ± 1.14 (S E M) days, which is at least 30 days longer than that previously reported for other callitrichid species. Both E1 and E2 reached their maximum levels during midpregnancy but showed a rapid decline at parturition. Gestational levels of CG were first detectable approximately 20 days after the LH peak and continued to be elevated for approximately 80 days. The Sub-Human Primate Tube Test (SHPTT) for pregnancy did not detect the LH Peak and was less sensitive than other methods in detecting CG. Two RIA methods and a bioassay technique could not distinguish between LH and CG. We concluded that monitoring both estrogen and LH concentration was needed to determine when ovulation occurs in the cotton-top tamarin, since peak values of estrogen are seen after the ovulatory LH peak. Also, these tamarins were pregnant the majority of the time, indicating an unusually high fertility rate in contrast to most noncallitrichid primate species.

Significance of persistant values of estrogen (ER) and progesterone (PR) receptors in successive samples of human breast cancer in the course of disease

Significance of persistant values of estrogen (ER) and progesterone (PR) receptors in successive samples of human breast cancer in the course of disease