PgR Levels Research Articles

Megestrol acetate as primary hormonal therapy for advanced breast cancer.

The records of 133 patients treated with megestrol acetate as primary hormonal therapy for advanced breast cancer were reviewed retrospectively, using International Union Against Cancer (UICC) criteria for response. The median age was 65 years, 121 patients were over age 50, and the age range was 39 to 94 years. Response rates (complete response [CR] + partial response [PR]/total) by qualitative receptor level, with levels of 10 fmol/mg of protein considered positive, were as follows (ER = estrogen receptor, PgR = progesterone receptor): For ER + PgR+, 13 + 15/56 (50%); for those with one positive receptor, 0 + 12/47 (26%); for ER - PgR-, 0 + 0/12 (0%); and for receptor-unknown cases, 2 + 3/18 (14%). Response for ER less than 30 fmol/mg was 2 + 6/39 (21%); for ER 30 to 50, 1 + 5/16 (40%); and for ER greater than 50 fmol/mg, 11 + 15/56 (46%). For PgR less than 30, response was 0 + 6/37 (16%); for PgR 30 to 50 fmol/mg, 1 + 4/14 (36%); and for PgR greater than 50 fmol/mg, 12 + 13/54 (46%). For the 75 patients with a disease-free interval (DFI) of 2 years or less, the response rate was 5 + 1/75 (8%), and for the 58 patients with DFI greater than 2 years, 10 + 12/60 (37%). For patients with prior chemotherapy, 3 + 8/49 (22%) had an objective response. For those with no prior chemotherapy, 12 + 19/84 (37%) responded. Response by dominant site of disease was as follows: soft tissue 12 + 9/43 (49%), bone 2 + 13/49 (31%), viscera 2 + 5/41 (17%). Of these seven patients with visceral dominant disease who responded, all had PgR levels greater than 50 fmol/mg, all but one had an ER level over 100 fmol/mg, all but one were over age 65, and all but two received no prior chemotherapy. We conclude that megestrol acetate is effective initial hormonal therapy for patients with advanced breast cancer. It may have some role to play in the treatment of carefully selected cases with visceral disease.

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.

Progesterone receptor activity and relapse-free survival in patients with primary breast cancer: The role of adjuvant chemotherapy

The prognostic significance of progesterone receptor activity (PgR) with regard to the estimated relapse-free survival (RFS) was studied in 350 one-center patients with primary breast cancer. All receptor assays were performed in one laboratory; PgR levels greater than 10 fmol/mg protein were considered positive. Univariate as well as multivariate statistical analyses were used to examine the prognostic significance of several variables. Eighty-nine of the 350 patients received adjuvant CMF chemotherapy (cyclophosphamide, methotrexate, and 5-fluorouracil). The median observation period was 69 months (range 12-125 months). In the group of 261 patients who did not receive adjuvant CMF, the PgR-status lacked prognostic significance; only the lymph node status significantly affected the RFS (p less than 0.00001). In contrast, in the CMF-treated group of patients, the PgR-status was the most powerful predictor of recurrence (p less than 0.001). Premenopausal CMF-treated patients with PgR+ tumors had a significantly longer RFS than those with PgR- tumors (p less than 0.02). The present data urge the need for a reappraisal of the prognostic significance of PgR and of the mechanism of action of adjuvant chemotherapy in primary breast cancer.

Correlation of multiple steroid receptors with histological type and grade in human ovarian cancer.

One hundred eight human ovarian cancers were analyzed for estrogen (ER), progestin (PgR), and androgen (AR) receptors. The receptor levels were related to histological type and grade of the tumor. There were 103 common epithelial carcinomas subdivided into serous (36), endometrioid (36), mucinous (18), clear cell (5), malignant Brenner (3), mixed epithelial (2), and undifferentiated (3) types. Of the remaining five, four were sex cord-stromal tumors and there was a single case of germ cell tumor. ER was detected in 52%, PgR in 52%, and AR in 91% of the cases. There was no correlation between the presence of ER and AR and the tumor histology. The presence of PgR correlated with the grade of endometrioid carcinoma, while no clear correlation existed for the other tumor types. PgR was absent in the three undifferentiated carcinomas. Interestingly, high PgR levels were detected in the three granulosa cell tumors.

Progesterone receptor activity and the response to the first endocrine therapy in advanced breast cancer

The predictive value of the progesterone receptor activity (PgR) was studied in a group of 84 patients with estradiol receptor (ER) positive advanced breast cancer who received their first endocrine treatment (tamoxifen or ovariectomy), with special emphsis on the timing of the receptor analysis. All patients were treated at 1 center and receptor analyses performed in 1 laboratory. In the group of 27 patients with PgR analysis performed immediately prior to the start of treatment, 14 out of 18 PgR+ve and only 2 out of 9 PgR−ve patients responded (P < 0.02). In contrast, when PgR was analysed >6 months prior to the start of treatment, the response rates for PgR+ve and PgR−ve patients did not differ significantly: 55% vs. 33% respectively. With regard to quantitative rather than qualitative PgR data, PgR levels exceeding 100 fmol/mg protein irrespective of ER levels, are an excellent indicator of hormonal responsiveness with a response rate of more than 80%, even if PgR analyses are performed long before the start of treatment.

Endometrial estradiol and progesterone receptors in patients with luteal phase defects and endometriosis

Endometrial cytosol estrogen receptors (ERs) and progesterone receptors (PgRs) were quantitated in postovulatory endometrial biopsy samples of patients with luteal phase defect (LPD), those with endometriosis, and normal control subjects. Serum levels of estradiol (E2) and progesterone (P), obtained on the day of the biopsy, were also measured. No significant differences among endometrial ER, PgR, serum E2, and P levels were detected between the patients with endometriosis and normal control subjects. Although ER concentrations in the luteal defect group did not differ from those of control subjects, the PgR levels in day 20 to 23 endometrium were significantly higher. Mean serum E2 and P levels in the group with luteal insufficiency were significantly lower than those of the control subjects. Our data suggest that in patients with LPD the increase in PgR levels during the midluteal days is compatible with a relative deficiency of P secretion by the corpus luteum.

Estrogen and progesterone receptors in the human vagina.

Estrogen (E) and progesterone (Pg) receptor (R) levels were determined in the human vagina in relation to menopausal status, day of ovarian cycle and pregnancy. The results obtained confirmed that the human vagina contains ER and, in addition, demonstrated for the first time the presence of PgR in this organ in humans. In cycling women, ER and PgR did not vary significantly during the ovarian cycle; however low (less than or equal to 10 fmoles/mg cytosol protein) concentrations of PgR were more frequently (6 out of 8 cases) detected during the secretory phase. No substantial difference was seen in ER and PgR values between anterior and posterior wall of the vagina. In postmenopausal patients the levels of ER (range: 10-83 fmoles/mg) were similar to those found in premenopause (range: 12-78 fmoles/mg). As regards PgR, the majority (14 out of 20) of vaginae were devoid of PgR, 4 had a very low (less than or equal to 6 fmoles/mg) PgR content and only 2 cases had a PgR level higher than 10 fmol/mg cytosol protein. In pregnant patients (6th to 8th week) ER were found in all vaginae, while PgR were present only in some cases (3 out of 8). It was concluded that the behavior of ER in the human vagina seems different from that in the human endometrium, since ER levels do not vary in relation to changes in the concentrations of sexual hormones in the circulation. On the contrary, PgR levels appear to depend on blood estradiol and progesterone concentration, as in other target tissues.

Progesterone receptors in breast cancer

A review of recent data which provides considerable support for the routine assay of estrogen receptors (ERs) and progesterone receptors (PgRs) in patients with metastatic breast cancer is reported. Assays for PgRs in breast cancer estrogen dependence of PgRs in experimental breast cancer cells and clinical correlation and PgRs are the main topics reviewed. It was shown that a relationship exists between presence of estrogen and presence of PgR. However this is not to say that estrogen-responsive tumor growth and estrogen-induced PgR are inexorably linked. At least 2 tumors grew in the absence of estrogen so that their growth may be considered autonomous whereas their PgRs declined and could thus be considered estrogen dependent. Data in experimental breast cancer suggest PgR is estrogen-dependent. Data indicate that estradiol acts directly and not as an intermediary hormone to induce PgR. It is emphasized that PgR induction is only 1 product of estrogen action. Some tumors grow in castrate rats so that growth can be considered estrogen autonomous while tumor PgR levels decline and could therefore be considered estrogen dependent. It is predicted that tumors regressive while on high dose estradiol would have elevated PgR levels. The studies strongly suggest that estrogen stimulation of PgR involves ERs. ERs and PgRs were measured in more than 500 breast tumor specimens. The results indicate that patients whose tumors lack both receptors have virtually no chance of responding to endocrine therapy and should receive combination chemotherapy.

Estrogen - and gestagen - receptors in ovarian carcinoma.

Estrogen (ER) - and progestagen (PgR) - receptors were estimated by a DCC method using Scatchard plot analysis In tissue samples of 68 patients with ovarian carcinomas. The mean ER and PgR levels were at 52 and 74 fmol/mg cytosol protein, respectively. ER+ PgR+ records were noted in 32.4%, ER+ PgR- in 26.4%, ER- PgR+ in 7.4%, and 33.8% presented with ER- PgR-. In the surviving group 44.1% had Er+ PgR+, whereas the patients who died had an incidence of only 20.5% ER+ PgR+. In addition, the incidences of ER+ PgR+ in stage I plus II and stage III plus IV patients were 42.6 and 29.5%, respectively. Furthermore, higher incidences of ER+ PgR+ were recorded in patients older than 60 years of age (63%) than in younger subjects (36%). The present data combine to suggest that receptor assays should become a useful tool in the management of patients bearing ovarian carcinomas. In addition, ER and PgR determinations provide a prognostic index and may improve the possibility to predict which well-differentiated stage I ovarian carcinomas are likely to recur.

Hormone dependency in N-nitrosomethylurea-induced rat mammary tumors.

The majority (87%) of N-nitrosomethylurea-induced rat mammary tumors regressed within 1 week after hypophysectomy (hypox). After a hypox-induced tumor regression, ovine PRL (oPRL), and 17 beta-estradiol (E2) were administered separately or in combination in order to define the individual role of these hormones in regulating tumor growth and influencing estrogen (E), progesterone (Pg), and PRL receptor (R) levels. Administration of E2 (2.5 micrograms twice daily) or oPRL (20 IU daily, started 5 days after hypox and continued for 10 days, resulted in stabilization of tumor growth. Simultaneous administration of E2 and oPRL resulted in a synergistic effect and reactivation of tumor growth. ER levels in mammary tumors were significantly lower than those in the control 15 days after hypox (P less than 0.01). Treatment with E2, oPRL, or both simultaneously had no significant effect on ER levels. A significant decline in PgR levels was noted at both 5 and 15 days after hypox. Whereas treatment with oPRL had no significant effect on PgR levels, E2 administration either alone or in combination with oPRL restored PgR levels to control values. PRLR levels were unchanged from control values at 5 days, but significantly declined (P less than 0.005) 15 days after hypox. Treatment with E2, oPRL, or both hormones simultaneously partially maintained PRLR and prevented the decline to the extremely low level noted in the untreated group. We conclude that the growth of nitrosomethylurea-induced rat mammary tumors is dependent on both E2 and PRL. There was a synergistic effect between E2 and PRL on tumor growth but not on ER, PgR, or PRLR. Neither E2 nor PRL had any significant effect on ER after hypox. PgR is under E2 control. Either E2 or PRL or both hormones were able to maintain PRLR in mammary tumors after hypox.

Maternal nutrition and the sex ratio at birth: River, J. P. & M. A. Crawford: Nature, [formula omitted]: 297, 1974. Nuffield Institute of Comparative Medicine, Zoological Society of London, Regent's Park, London NW1 4RY, England

The objective of this study was to investigate the effects of inhibiting the epidermal growth factor receptor (EGFR) pathway on meiosis blockage and resumption, mRNA expression of genes involved in oocyte maturation and cumulus expansion, and embryo development. Bovine cumulus-oocyte complexes (COCs) were cultured for 15 h in the presence of the EGFR inhibitor (AG1478) and follicular hemisections (FHS). Most of the oocytes (89.3%) remained at the germinal vesicle (GV) stage when cultured in the presence of FHS and 5 μM AG1478. The inhibitory effect was reversible as most oocytes (83.8%) completed meiosis after additional 20 h maturation. Embryo development to the blastocyst stage was similar (P > 0.05) between FHS and 5 μM AG1478 treated (39.3%) and control (41.1%) groups. In cumulus cells, mRNA abundance of early growth response protein 1 (EGR1), tumor necrosis factor alpha-induced protein 6 (TNFAIP6) and hyaluronan synthase 2 (HAS2) genes, and phosphorylated extracellular regulated kinase (p-ERK1/2) protein were lower in COCs treated with AG1478 plus FHS compared with FHS alone (P < 0.05). In granulosa cells of FHS, AG1478 treatment reduced transcript levels of PGR and ADAMTS1 (P < 0.05). The inhibitory effect of AG1478 on meiotic progression was not reverted by treatment with angiotensin II (ANG II) or prostaglandins (PGF2α or PGE2). This study demonstrates that inhibition of EGFR in the presence of FHS is a reliable approach to promote reversible arrest of bovine oocytes at the GV stage.