Comparative analysis of endometrial receptivity in young women with endometrial and ovarian infertility factors

e13078 Background: Differences in clinical outcomes have been observed between pts with de novo (dnMBC) and recurrent metastatic breast cancer (rMBC). We investigated the prognostic value of ER and PR expression levels in primary tumors in HR+/HER2 dnMBC and rMBC treated with CDK4/6i and ET. Methods: We retrospectively analyzed clinical data of HR+/HER2- MBC pts administered palbociclib (PAL), ribociclib (RIB) or abemaciclib (ABM) combined with first- or second-line ET. Duration of CDK4/6i treatment (dCDKi), second progression free survival (PFS2), and overall survival (OS) were analyzed using R statistical software (version 4.4.1). Results: A total of 2120 patients (pts) from 16 Polish cancer centers treated between Sep 2017 and Dec 2024 were analyzed: 1120 (52.8%) and 1000 (47.2%) with rMBC and dnMBC, respectively; mean age 62±12 years, luminal A and B cancers 784 (41.8%) and 1093 (58.2%) cases, respectively. ER expression of 0-10%, 11-66%, and 67-100% was found in 36 (1.7%), 163 (7.7%), and 1921 (90.6%) cases and respective PR expression in 524 (25.0%), 510 (24.4%), and 1059 (50.6%) cases. 707 pts (33.3%) received PAL, 1008 (47.5%) RIB, and 405 (19.1%) ABM; 1273 (60%) received aromatase inhibitor and 847 (40%) fulvetrant. The median follow-up was 31.4 months. Cancer phenotype and PR expression level were prognostic in dnMBC and rMBC, whereas ER expression level only in dnMBC (Table 1). Conclusions: Our results indicate biological differences between dnMBC and rMBC that may impact treatment efficacy. These differences may be due to intrinsic or acquired resistance and support the need for repeat biopsy for rMBC. dnMBC Expression (%) dCDKi PFS2 OS ER 0-6667-100 14.4 (8.5-20.8)23.1 (19.8-25.4)p=0.004 26.4 (16.5-40.5)38.1 (36.4-42)p=0.006 33.1 (20.2-RN)52.3 (45.6-66.8)p=0.003 PR 0-1011-6667-100 16.9 (13.4-22.4)18.0 (15.1-24.3)26.4 (22.9-35.4)p<0.001 29.8 (24.5-39.6)31.9 (29.2-39)43.8 (38.5-55.4)p<0.001 41.2 (34.5-66.8)46.8 (41.3-NR)58.4 (47.6-85.5)p<0.001 Phenotype luminal Aluminal B 28.6 (23.3-35.4)18.4 (16.1-23.0)p<0.001 47 (40.5-63.5)33.1 (30.1-37.3)p<0.001 64.4 (47.6-NR)44.3 (39.8-54.2)p<0.001 rMBC Expression (%) dCDKi PFS2 OS ER 0-6667-100 13.9 (10.4-18.3)16.2 (14.8-18.7)p=0.23 32.7 (22.2-46.4)30.7 (28.5-33.5)p=0.66 37.2 (27.9-68.6)40.8 (38.2-47.1)p=0.5 PR 0-1011-6667-100 13.0 (9.4-15.1)16.1 (13.0-19.7)20.0 (17.2-22.9)p<0.001 22.2 (19.5-28.6)35.2 (31.7-40.5)32.3 (27.8-39.6)p<0.001 29.7 (24.4-37.2)47.6 (40-87.4)45.4 (38.8-68.9)p<0.001 Phenotype luminal Aluminal B 19.3 (15.9-22.0)11.4 (9.4-14.1)p<0.001 33.6 (29.3-40.7)22.2 (20-28.3)p<0.001 47.6 (38.8-61.6)29.8 (25.4-34.4)p<0.001 RN, not reached; dCDKi, PFS2, OS are in months.

Simple SummaryAlthough ER expression levels affect the prognosis of breast cancer, studies about PR expression levels are insufficient. Furthermore, there is a knowledge gap between single HR-positive and double HR-positive, especially according to PR expression. As HR positivity is an important prognostic factor, particularly in YBC patients, this research was conducted in a prospective cohort with only YBC patients in order to find out whether the expression of PR modifies the clinical course of breast cancer. We investigated clinicopathologic features and prognosis of ER-positive/HER2-negative breast cancer after stratifying them according to PR expression levels. Conclusively, low PR expression was correlated with worse clinicopathologic characteristics, and associated with increased risk of recurrence, distant metastasis, and death compared with strong PR expression group. Low PR might be a prognostic factor of ER-positive/HER2-negative YBC.Background: Although estrogen receptor (ER) expression levels affect the prognosis of breast cancer, studies about progesterone receptor (PR) expression levels are insufficient, especially in young breast cancer (YBC). The purpose of this study was to compare clinical characteristics and prognosis according to PR expression levels in invasive breast cancer patients. Methods: A prospective cohort study was conducted to identify YBC patients with invasive carcinoma diagnosed at an age of less than 40 years old between 2013 and 2018. Clinicopathologic features and prognosis of ER-positive and human epidermal growth factor receptor 2 (HER2)-negative patients were investigated. Patients were stratified into strong PR (PR-positive cell proportion > 10%), low PR (PR-positive cell proportion = 1~10%), and PR-negative (PR-positive cell proportion < 1%). Results: Among 458 patients enrolled, 386 (84.3%), 26 (5.7%), and 46 (10.0%) were categorized into strong PR, low PR, and PR-negative groups, respectively. The median follow-up duration was 58.6 months. Compared with the strong PR group, low PR and PR-negative groups were more likely to have high Ki-67 and a high nuclear grade. Low R and PR-negative groups had significantly worse disease-free survival (DFS) and distant metastasis-free survival (DMFS) than the strong PR group (p = 0.0033, p = 0007). Low PR group had an even higher risk of distant metastasis than PR-negative patients. Low PR patients and PR-negative had significantly lower overall survival (OS) rates than strong PR. Conclusion: Low PR might be a prognostic factor of ER-positive/HER2-negative in YBC.

BACKGROUND: In patients of reproductive age with endometrial hyperplasia without atypia, hormonal treatment, and prognosis of response remain relevant issues.&#x0D; AIM: To increase the effectiveness of hormonal therapy for endometrial hyperplasia in patients of reproductive age with abnormal uterine bleeding, considering the receptivity, and proliferative activity of the endometrium.&#x0D; MATERIALS AND METHODS: A total of 179 patients of reproductive age with abnormal uterine bleeding and endometrial hyperplasia were examined. After the removal of the endometrial tissue, hormonal therapy was performed for 6 months: 101 patients received dydrogesterone 20 mg/day, and 78 patients received norethisterone acetate 10 mg/day. The expression levels of estrogen receptor- (Er), progesterone receptor (PR), and Ki67 in the endometrial tissue were determined by immunohistochemistry at baseline and 3 months after the treatment. The comparison group consisted of 18 women without gynecological pathology. Variation statistics methods were used to process the data, the differences between the indicators groups of patients were considered significant at p 0.05.&#x0D; RESULTS: Before treatment, the expression levels of ER, PR in both compartments, and Ki-67 in the glands were lower (p 0.05) in the endometrial hyperplasia group than in the control group. Remission was achieved in 77 (76.24%) (dydrogesterone) and 62 (79.49%) (norethisterone acetate) patients. Initially, the expression level of ER in the glands and stroma of endometrial hyperplasia was lower (p 0.05) than that in the comparison group; the resistant group had a lower (p 0.05) response to treatment. The expression of PR in the resistant group was lower (p 0.05) than that in the comparison group and remission group. The expression level of Ki67 in the response group was lower than that in the comparison group (p 0.05), and the expression in the stroma was lower than that in the resistant group (p 0.05). After treatment in both compartments, the expression levels of ER and PR were lower in the resistant group than in the comparison group and response group (p 0.05). A logistic regression equation was obtained with a set of predictors: ER (glands) + PR (glands and stroma) + Ki-67 (stroma) with a potential response to therapy of 93%.&#x0D; CONCLUSIONS: The specified predictive model is promising. The therapy was effective in 93% of cases.

The present study examined the immunoexpression of the estrogen receptor (ER), the progesterone receptor (PR), B‑cell lymphoma 2 (Bcl‑2), cyclooxygenase‑2 (Cox‑2) and Ki67 in endometrial polyps and their association with obesity. In total, 515 premenopausal and postmenopausal females undergoing hysteroscopy with histological diagnosis of benign polyps were included. The immunohistochemical expression of the ER, PR, Bcl‑2, Cox‑2 and Ki67 was compared between obese and non‑obese females. The median final score demonstrated a higher PR expression in the stromal and glandular compartments of postmenopausal obese females as compared with no‑obese females. However, in this group, there was no difference in regard to the ER. No difference in hormone receptor expression was identified among premenopausal females. In postmenopausal females, the immunoexpression of Cox‑2 and Bcl‑2 in the glandular epithelium was higher in obese than in non‑obese females. Among premenopausal females, obese females demonstrated a higher Bcl‑2 expression in the glandular epithelium than non‑obese females. There were no differences in Ki67 expression between obese and non‑obese females. Polyps from obese females had a higher PR expression in the glandular and stromal compartments. The expression of Cox‑2 and Bcl‑2 was higher in the glandular compartment. These data suggested that the etiology and pathogenesis of polyps in obese females appear to be associated with the PR, the inhibition of apoptosis and cellular mechanisms linked with inflammation.

EphA2 is a tyrosine kinase receptor in the ephrin family that is implicated in oncogenesis and angiogenesis. The objective of the current investigation was to study the role of EphA2 in endometrial cancer and its relation to steroid hormone receptor expression. EphA2, estrogen receptor (ER), progesterone receptor (PR), and Ki-67 expression levels were evaluated using immunohistochemistry in 139 endometrioid endometrial carcinoma (EEC) samples and in 10 benign endometrial samples. Samples were scored by 2 investigators who were blinded to clinical outcome. The results were correlated with clinicopathologic characteristics using univariate and multivariate analysis. A P value <.05 was considered statistically significant. High expression of EphA2 was detected in 48% of EEC samples versus 10% of benign samples. EphA2 overexpression was associated significantly with high disease stage (P = .04), high tumor grade (P = .003), increased depth of myometrial invasion (P = .05), low ER expression (P = .01), low PR expression (P = .006), and high Ki-67 expression (P = .04). Low ER and PR expression levels were associated with high tumor grade, positive lymph nodes, high Ki-67 expression, and high EphA2 expression. On univariate analysis of all patients, high EphA2 expression was associated significantly with shorter disease-specific survival (DSS) (P < .001). On multivariate analysis, age (P < .001), high disease stage (P = .002), and high EphA2 expression (P = .04) were independent predictors of poor DSS. EphA2 overexpression was associated with aggressive phenotypic features in EEC and was associated inversely with ER and PR expression. Thus, EphA2 may be an important therapeutic target, especially in patients with hormone receptor-negative endometrial carcinoma.

11563 Background: The efficacy of hormone therapy (HT) is controversial in patients with a lower level of estrogen receptor (ER) expression or absence of progesterone receptor (PR). The aim of this study is to compare the efficacy of adjuvant HT and chemotherapy (CT) +HT in patients with different levels of ER and PR expression. Methods: 190 patients with nonmetastatic hormone responsive breast cancer and a median follow-up period of 49 months were included in this study. Fifty percent of patients were premenopausal and 63% were node positive. Both HR were evaluated by immunohistochemistry. ER expression score, as assessed by the ratio or percentage of cells stained positive, was evaluated in 4 groups: negative (8%), <1/3 (29%), ≥1/3–2/3 (18%), >2/3 (45%); whereas, patients were classified as positive or negative (19%) with respect to PR expression. The number of patients who received CT/HT and HT in the high ER score group and ER+/PR- groups were 63 (77%)/19 (23%) and 27 (82%)/6 (18%), as compared to low ER 44 (83%)/9 (17) and ER+/PR+ groups 121 (81%)/7 (21%), respectively. The prognostic impact of these factors on overall (OS) and disease-free survival (DFS) were analyzed by the Kaplan-Meier method. Results: The use of adjuvant CT was significantly higher in patients with node positive disease regardless of ER score or PR expression. OS and DFS were significantly lower in patients with a negative ER (p=0.02). There was no difference in either endpoint with respect to expression score. There was a trend for poorer DFS and OS (p=0.08) in PR negative patients. There was no additional efficacy of CT with respect to ER score or PR expression. Conclusions: In this data set adjuvant CT seems to offer no additional benefit in ER positive patients regardless of ER score of PR expression. Other factors should be evaluated to predict endocrine resistance in patients with hormone responsive disease. Mature data with longer follow-up is pending. No significant financial relationships to disclose.

10526 Background: The association between breast cancer characteristics and survival with estrogen receptor (ER) and progesterone receptor (PR) expression has been primarily studied via binomial categories, ER-positive and ER-negative. In order to better characterize germline genetic influences on these markers, we investigated their IHC expression semi-quantitatively in cancer predisposition germline pathogenic variant (PV) carriers of the following genes: BRCA1, BRCA2, PALB2, TP53, PTEN, CDH1, ATM, CHEK2, and Lynch syndrome genes. The HER2 expression was also analyzed. Methods: We conducted a retrospective chart review of patients with germline panel genetic testing for cancer predisposition genes at Moffitt Cancer Center’s GeneHome clinic. Inclusion criteria included 1) women ≥18 years old, 2) breast cancer diagnosis, 3) cancer predisposition germline panel genetic test results, 4) available ER and PR expression levels, and 5) available HER expression and/or amplification status. ER, PR, and HER2 status were compared between PV carriers and non-PV carriers via Mann-Whitney U at p&gt;0.05. Results: A total of 847 cases were reviewed for the study. Among 658 patients with a breast cancer diagnosis and complete ER PR data, 365 cases (55.5%) were non-PV carriers and 293 cases (44.5%) carried a PV in at least one of the genes listed above. Among 635 cases with available HER2 expression/amplification status, 355 (55.9%) cases were non-PV carriers and 288 (45.4%) cases were PV-carriers. When compared with non-PV carrier controls, BRCA1 PV carriers’ breast tumors had significantly lower ER and/or PR expression. Further, BRCA2 and TP53 PV tumors also displayed moderately lower ER expression. Contrarily, CHEK2 tumors displayed higher ER and PR expression compared to controls. Further, BRCA1 and BRCA2 PV carriers were more likely to have HER2- breast cancers. Conclusions: Differences in ER, PR, HER2 expression levels were observed in germline PV carrier breast cancers, signaling differential impacts by germline PVs on the tumor evolution process. It is likely that tumor differences in PV carriers influence responses to therapies, including hormone therapy, anti-HER2 therapy, and subsequent survival.[Table: see text]

The objective of this study was to determine the effects of 2 different 5-alpha reductase inhibitors (finasteride and MK-0434) on the glandular and stromal compartments of hyperplastic canine prostates. In this study, dogs received 1 of the 2 compounds orally, at a dose of 1 mg/kg/day for 16 weeks; control dogs received a placebo. The morphological changes in the glandular and stromal compartments in the prostate were quantitated by a point-counting method on Masson's trichrome-stained sections. Treatment with 5-alpha reductase inhibitors resulted in significant (P < or = 0.05) decreases in mean prostatic volumes, microscopic evidence of prostatic atrophy, and significant (P < or = 0.05) decreases in the absolute volumes of the prostatic glandular and stromal compartments compared to controls. In finasteride-treated dogs, the mean percent change from baseline was: epithelium, -52; lumens, -58; fibrovascular stroma, -41; and smooth muscle, -29. In MK-0434-treated dogs, the mean percent change from baseline was: epithelium, -77; lumens, -58; fibrovascular stroma, -38; and smooth muscle, -42. The effect on the glandular compartment in dogs treated with MK-0434 was slightly greater than in dogs treated with finasteride; however, the effect on the stroma was similar. These results clearly demonstrate that inhibition of 5-alpha reductase enzyme activity affects growth and maintenance of both glandular and stromal compartments of dog hyperplastic prostates. It is likely that the decrease in size of the prostate in finasteride-treated (Proscar) men is due to shrinkage of both glandular and stromal compartments.

High body mass index (BMI) is associated not only with a higher incidence of breast cancers but also with poorer prognosis. It is speculated that both enhanced production of estrogens and other factors associated with obesity are involved in these associations, but the biological characteristics associated with high BMI have yet to be thoroughly identified. We studied 525 breast cancers, focusing on biological differences between tumors associated with high and low BMI and by immunohistochemically defined intrinsic subtype. Ki67 expression levels were used to differentiate luminal A from luminal B estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)-breast cancers. Premenopausal patients with high BMI showed a significantly higher frequency of lymph node metastasis (46.4 % vs. 22.9 %, P = 0.005) and tended to have a larger tumor size (P = 0.05) and higher nuclear grade (P = 0.07) than those with low BMI. These differences were not observed among postmenopausal patients. BMI was not associated with distribution of breast cancer subtypes, and ER, progesterone receptor (PR), and Ki67 expression levels of each subtype showed no differences between high and low BMI among premenopausal patients. Higher BMI might influence aggressive tumor characteristics among premenopausal patients, but its influence on ER, PR, and Ki67 expression levels seems to be limited.

Changes in glandular and stromal estrogen and progesterone receptor isoform expression in eutopic and ectopic endometrium following treatment with the levonorgestrel-releasing intrauterine system

The purpose of the study was to determine the level of expression of estrogen and progesterone receptors in endometrial tissue and to determine their relationship with the level of vitamin D in the blood of women of childbearing age with endometrial hyperplasia and benign breast tumors. Materials and methods. Examination of women of reproductive age who were diagnosed with hyperplastic processes in the endometrium was carried out. The examined patients were divided into two groups: Group I – the comparison group, which included patients with endometrial hyperplasia without concomitant pathology; Group II – women who, along with endometrial hyperplasia, were diagnosed with benign breast disease in the form of mastopathy. An immunohistochemical method using the En Vision imaging system with diaminobenzidine was used to detect estrogen and progesterone receptors in the endometrium. Determination of 25-hydroxyvitamin D (25OHD) content in blood plasma was performed by enzyme-linked immunosorbent assay using the 25-Hydroxy test kit. Results and discussion. It was found that the level of estrogen receptors expression increases in all types of endometrial hyperplasia and is exacerbated in concomitant mastopathy. Along with the increase in the level of estrogen receptors expression in endometrial cells, the expression of progesterone receptors decreases. It was found that the amount of progesterone receptors in the main group decreased by 38.3% – in endometrial hyperplasia without atypia, by 46.3% – in atypical endometrial hyperplasia and by 20.4% – in endometrial polyps compared with the control group of women. Analysis of the results shows an association between the form of hyperplasia and the receptor phenotype of the endometrium. It is established that the greatest changes are observed in atypical endometrial hyperplasia, which are exacerbated during the development of proliferative processes in the mammary glands. The relationship between vitamin D deficiency and estrogen and progesterone receptor expression in women with endometrial hyperplasia has been shown. Thus, when the level of estrogen and progesterone receptors changes in the endometrium of women with endometrial hyperplasia and mastopathy, the concentration of vitamin D in blood plasma decreases. Conclusion. The development of hyperplastic processes in the endometrium and mammary glands occurs against the background of increased expression of estrogen receptors and decreased expression of progesterone receptors. At the same time in the blood plasma of patients a decrease in vitamin D was revealed

Background. Repeated implantation failure (RIF) is the most important problem in assisted reproductive technologies (ART). In the process of embryo implantation, accurate function of progesterone through progesterone receptors (PR) is crucial for establishment of a receptive endometrium. FKBP51 and FKBP52 are two co-chaperones acting as negative and positive regulators of PR function, respectively. Studies have shown that any deficiencies in expression of PR or its co-chaperones causes reproductive disorders. Materials and Methods. In this study we evaluated the PR protein expression by immunohistochemistry and expression of PR, FKBP51, FKBP52 genes by quantitative real-time PCR in endometrial tissue of normal and RIF women during the window of implantation. Results. Immunohistochemical studies showed that the PR protein expression in stromal cells is significantly higher in the endometrium of normal women than RIF women (P< 0.001). In addition, a significantly lower PR and FKBP52 gene expression was observed in endometrial tissue of RIF women compared to normal women (P< 0.001 and P< 0.001, respectively), whereas there was no significant difference in PR protein in epithelial cells (P= 0.3) and FKBP51 gene expression between the two groups (P= 0.6). Conclusion. The results indicate that altered expression of PR protein in stromal compartment and gene expression of PR and FKBP52 gene in endometrial tissue can be related to endometrial receptivity defects and occurrence of RIF

The analysis of estrogen receptor (ER) and progesterone receptor (PR) expression levels by immunohistochemistry is an important part of the initial evaluation of breast cancer and critically important in treatment planning. Anti-ERα (clone EP1) and anti-PR (clone PgR 1294) antibodies are in development for the Dako Omnis automated staining platform. These antibodies are not yet commercially available and are in performance evaluation, including the 4 international, multicenter studies reported here. For each antibody, a reproducibility study and a method comparison study was done in a randomized manner in order to test the antibodies under conditions closest to real-world user conditions. The reproducibility studies included 5 staining runs on the Dako Omnis with 20 formalin-fixed and paraffin-embedded human breast carcinoma specimens in 3 independent laboratories, and the method comparison studies included several hundred specimens stained on the Dako Omnis and on the Autostainer Link 48 platforms. Stained slides were evaluated for nuclear ER or PR expression according to American Society of Clinical Oncology/College of American Pathologists guidelines (≥1% cut-off for positive) by pathologists who were blinded from the staining method and specimen ID. For both anti-ERα (clone EP1) and anti-PR (clone PgR 1294) on the Dako Omnis, high reproducibility agreement rates were obtained on the interrun, interlaboratory, and interobserver endpoints. High concordance rates were observed between the specimens stained on the Dako Omnis platform and the Autostainer Link 48 platform. Staining quality was excellent for both anti-ERα (clone EP1) and anti-PR (clone PgR 1294) on the Dako Omnis. These results suggest that these antibodies are reliable and reproducible tools for immunohistochemistry analysis of ER and PR expression levels in formalin-fixed and paraffin-embedded breast carcinoma tissues on the Dako Omnis platform.

Sex steroids have been suggested to influence colorectal cancer (CRC) carcinogenesis. Also, exposure to exogenous hormones might contribute to its incidence. This study conducted to evaluate ER and PR expression as a prognostic factor in patients with CRC attending Sohag University Hospital (SUH) and Sohag Cancer Center (SCC). Materials and Methods: Tumor samples tested for Estrogen receptor (ER) / progesterone receptor (PR) expression using immunohistochemical staining (IHC). Association of this expression with overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS) were evaluated. Results: Thirty out of 50 CRC tissues were evaluable for hormone receptor expression. Expression of both ER and PR was cytoplasmic. ER and PR expressions were 60% and 76.66%, respectively. There was a significant difference between loss of ER expression and depth of invasion (p= 0.01). Also, ER and PR negative expression cases were significantly at higher risk for progression (p= 0.03; 0.009 respectively). High levels of ER and PR expression were associated with higher cumulative PFS at one year and at the end of follow up time (p=0.01; 0..02 respectively); however this did not reach statistical significance on Cox proportional hazards regression analysis for progression or OS (p= 0.05; HR= 0.22; p=0.5; HR=0.67 respectively) for ER level and (p=0.07; HR=0.22; p=0.6; HR=0.72 respectively) for PR level. Conclusions: This study suggests that lower ER/PR expression levels were associated with more extensive CRC primary tumors and poorer prognosis. These data suggest that ER/PR expression might possess a prognostic value for CRC cases.

Background Strong PgR expression predicts favorable outcomes for ER+ve HER2-ve breast cancer and has been proposed as a surrogate marker to distinguish between IHC-defined luminal A and luminal B subtypes. It is therefore possible that strong PgR expression may be able to predict tumor gene expression test results and independently identify tumors that are unlikely to be chemotherapy sensitive. PgR expression is traditionally determined by immunohistochemistry (IHC). Several validated RNA-based PGR expression tests have been developed that may outperform IHC. Methods We compared Oncotype DX RS with Oncotype DX reported PGR in 4 independent datasets which included 407 cases from the OPTIMA prelim trial. We further analyzed 251 OPTIMA prelim cases which had additional tumor gene expression data. All gene expression assays were performed by the test vendor, including PGR gene expression determined using the Mammatyper assay. PgR IHC was determined in a single laboratory on triplicate tissue micro-arrays using quantitative image analysis including a 10% manual quality control check. We analyzed PGR expression using cutoffs that correspond to approximately 20% staining; the standard Oncotype DX PGR assay is reported as positive if the score is &amp;gt;5.4, corresponding to approximately 1% staining by IHC. We used Spearman’s rank correlation coefficient to compare PGR data. Results The four Oncotype DX datasets consistently demonstrated that high Oncotype PGR expression was associated with a low RS (table). Combining the 3 validation data sets consisting of 633 cases, 70.9% had high PGR expression of which 92.7% had a an Oncotype RS ≤25. Approximately 50% of cases with low Oncotype PGR expression had an Oncotype RS &amp;gt;25. Mammatyper and Oncotype PGR were highly correlated (Rs = 0.9258, P&amp;lt; 0.001) in the OPTIMA prelim dataset (n=251), with only 8.4% of tumors having discordant high/low Mammatyper and Oncotype PGR scores. 93.2% of 176 Mammatyper high PGR expression cases had an RS ≤25. The Mammatyper PGR and PgR IHC correlation was weaker (Rs=0.763, P&amp;lt; 0.001); 87.2% of 211 cases with &amp;gt;20% staining had RS ≤25. PgR IHC staining had a bimodal distribution and there was little effect on the prediction of low RS score up to a 67% cut-off. Mammatyper and Oncotype PGR scores both appear to have a normal distribution. We took advantage of this to perform an exploratory analysis using a higher Mammatyper PGR cutoff. We were able to show superior prediction of a low RS (96.8%) but with a reduced proportion (50.2%) of high PGR score tumors. High PGR gene expression was weakly associated with low (≤60) Prosigna ROR_PT score and MammaPrint low risk (72.2% and 65.9% respectively) and with Prosigna and MammaPrint luminal A subtype (both 64.8%). Conclusion High progesterone receptor gene expression measured using locally performed RNA-based assays may allow the reliable prediction of Oncotype DX low-risk tumours. This analysis provides additional information for the clinical utility of PGR measurement. Additional data will be presented on the optimal PGR cutoff. OPTIMA prelim is registered as ISRCTN42400492 and funded by the UK NIHR Health Technology Assessment Programme, award number 10/34/01. Views expressed are those of the authors and not those of the HTA Programme, NIHR, NHS or the Department of Health. Table. Oncotype DX RS and PGR in 4 datasets Distribution of RS according to %cases with high or low PGR Citation Format: Robert Stein, Ralph Wirtz, Andrea Marshall, Jane Bayani, Sebastian Eidt, Claudia Schumacher, Hans-Peter Sinn, Andreas Schneeweiss, Andreas Makris, Iain Macpherson, Luke Hughes-Davies, Tammy Piper, Monika Sobol, Georgina Dotchin, Helen Higgins, Sarah Pinder, Abeer Shaaban, Janet Dunn, John MS Bartlett. Can high progesterone receptor (PgR) expression identify tumours with low-risk tumour gene expression scores? [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-16-02.