Estrogen Progesterone Receptor Research Articles

Discordance of estrogen and progesterone receptors after neoadjuvant chemotherapy in locally advanced breast cancer.

This study aimed to compare hormone receptor (HR) status before and after neoadjuvant chemotherapy that is discordance in locally advanced breast cancer patients, which are amenable for surgery. The secondary objective was to study the correlation between tumor response and HR expression. The duration of the study was from August 2018 to December 2020. A total of 23 patients were selected as per certain inclusion criteria. American Society of Clinical Oncologys methodology was used to analyze estrogen receptor (ER) and progesterone receptor (PR) status of histopathology specimen. For study purposes, patients were classified into four groups after core biopsy of breast lump and after definitive surgery (post-NACT (neoadjuvant chemotherapy)) - Group A (ER+, PR+), Group B (ER+, PR-), Group C (ER-, PR+), and Group D (ER-, PR-). ER discordance was found to be (2/23) 8.69% (P value 0.76). PR discordance was (4/23) 17.39%. PR discordance was found to be higher than ER discordance. Changes in staining patterns in ERs were seen in 14 patients (93.33%). Changes in staining percentage in PRs were seen in eight patients (80%). It was found that both receptor-positive and negative diseases had an equal proportion of stable disease. From the study, it is noted that performing ER PR study twice (before and after chemotherapy) is necessary as discordance is noted and this may impact the further treatment strategy.

Estrogen Receptor, Progesterone Receptor Profile in Association with CK 5/6 Immunohistochemical Status in Proliferative, Preinvasive and Malignant Epithelial Neoplasms of Breast

Introduction: Breast carcinomas have shown increasing incidence across the world over the recent few years. The different epithelial cells play a role in the pathogenesis of different breast lesions consistent with the varying cytokeratin (CK) expression profiles. The luminal cells express CK 8 and 18 while myoepithelial cells show CK 5/6 and CK 17 expression. Triple Negative Breast Cancers (TNBC) (hormonal receptors and Human Epidermal growth factor Receptor 2 (HER2)/neu negative) express basal cytokeratins and histopathologically show metaplastic to medullary features while luminal breast cancers with glandular differentiation show hormonal receptor or HER2 expression. Also basal cells are characteristic of benign lesions like epithelial hyperplasia, fibroadenoma etc while being absent in atypical hyperplasia and preinvasive lesions. Aim: To study cytokeratin 5/6 and Estrogen Receptor/Progesterone Receptor (ER/PR) expression pattern in proliferative, preinvasive and malignant lesions of breast. Materials and Methods: An observational cross-sectional study was undertaken in the Department of Pathology in a tertiary care hospital in East India, from January 2019 to June 2020. A total of 41 samples diagnosed as proliferative (Usual Ductal Hyperplasia (UDH)/Atypical Ductal Hyperplasia (ADH), preinvasive Ductal carcinoma in Situ (DCIS) and invasive breast carcinomas were selected by systematic random sampling. Immunohistochemical examination was done using monoclonal antibodies against Cytokeratin 5/6 and ER/PR/HER2 after obtaining thin sections from formalin fixed paraffin embedded blocks and retrieval of antigen. The data was interpreted by light microscopy using a semi-quantitative method with respect to prefixed parameters and statistical analysis was done by Chi-square test and Fisher’s exact test using Statistical Package for the Social Science (SPSS) version 25.0. Results: Of the 41 case three were of proliferative lesions (UDH+ADH), one of the case (UDH) constituting 33.3% of total showed positive CK 5/6 expression and two of the cases (ADH) mounting to 66.7% of total showed negative CK 5/6 expression. Of two preinvasive lesions (DCIS), 100% of them showed negative CK 5/6 expression. On categorisation of carcinoma cases into molecular subgroups as indicated by surrogate immunohistochemical expression, it was found that majority of the cases (20) exhibited Luminal-A Like molecular profile constituting 55.6% of total. This was followed by an equal incidence of HER2/neu enriched (non luminal) and triple negative phenotypes, both being five in number, individually constituting 13.9%. Both Luminal B-like (HER2-positive) and Luminal B-like (HER2-negative) were three in number contributing to 8.3% of total each. Out of 36 malignant cases, five of them showed positive CK 5/6 expression constituting 13.9% of the total while rest of them showed (31) negative CK 5/6 expression constituting 86.1% of total. All these five cases showing positive CK 5/6 expression belonged to triple negative molecular subtype and this association between the molecular subtypes and CK 5/6 expression pattern was statistically significant as the p-value was 0.0034 (<0.05). Of total five TNBC cases, two of the cases (40%) were reported to have weak positive CK 5/6 immunostaining, while three (60%) of the cases had moderate intensity. Still none of these cases exhibited strong immunostaining. The single UDH case reported in present study, exhibited strong positive immunostaining with CK 5/6. Conclusion: The proliferative lesions consisting of both luminal and myoepithelial cells like UDH showed strong membranous and cytoplasmic expression while ADH, DCIS, and invasive breast carcinoma comprising primarily of luminal epithelial cells were negative for basal cytokeratin 5/6 expression. These group of breast carcinomas belonged to other immunophenotype categories apart from TNBC. However, a special immunophenotype TNBC group, negative for ER/PR and HER2/neu was strikingly positive for CK 5/6 and a statistically significant association was found.

Estrogen Receptor- And Progesterone Receptor-Positive Thresholds in Predicting the Recurrence of Early Low-Risk Endometrial Cancer.

Background:Estrogen receptors (ER) and progesterone receptors (PR) have important prognostic value in endometrial cancer, but there is no recognized positive immunohistochemical threshold for predicting the recurrence of early low-risk endometrial cancer. The purpose of this study was to clarify the optimal positive thresholds of the immunohistochemical parameters the ER and PR in early low-risk endometrial cancer.Methods:A total of 332 patients with stage IA endometrial cancer were enrolled from the First Affiliated Hospital of Chongqing Medical University and People’s Hospital of Sha ping ba District in Chongqing between January 2013 and December 2018. First, univariate and multivariate Cox regression analyses were used to analyze the correlation between various clinical factors and the prognosis of early low-risk endometrial cancer. Then, the receiver operating characteristic curve (ROC curve) and Youden index were used to determine the positive thresholds of ER and PR.Results:The positive thresholds of ER and PR for predicting the recurrence of early low-risk endometrial cancer were 12% and 8%, respectively. Multivariate analysis showed that ER (P = 0.004), PR (P = 0.026), and p53 (P = 0.021) were risk factors for the prognosis of patients with early low-risk endometrial cancer. The recurrence-free survival and the overall survival in the low ER group and PR group were much lower than those in the high ER group and PR group (P < 0.001 of all).Conclusions:ER and PR positive thresholds of 12% and 8%, respectively, are the most suitable for predicting the recurrence of early low-risk endometrial cancer.

Implications of Oncoplastic Breast Surgery on Radiation Boost Delivery in Localized Breast Cancer.

BackgroundOncoplastic partial mastectomy (OPM) is a technique utilized to improve aesthetic and survivorship outcomes in patients with localized breast cancer. This technique leads to breast tissue rearrangement, which can have an impact on target definition for boost radiotherapy (BRT). The aim of this study was to determine if the choice of surgical technique independently affected the decision to deliver a radiation boost.Materials and methodsThis was a retrospective study of patients treated between January 2017 and December 2018. We selected consecutive patients based on surgical procedure: 50 undergoing standard breast-conserving surgery and 50 having had an OPM. The primary outcome was average treatment effect (ATE) of surgery type on reception of BRT. Secondary outcomes included ATE of surgery type on the time to reception of radiotherapy and incidence of ipsilateral breast tumor recurrence (IBTR). The ratio of boost clinical target volume (CTV) to pathologic tumor size was also compared between the two groups. Treatment effects regression adjustment and inverse-probability weighted analysis was used to estimate ATEs for both primary and secondary outcomes.ResultsFor the entire cohort, the median age was 64 years (range: 37-88 years). The median tumor size was 1.5 cm (range: 0.1-6.5 cm). The majority of patients were with ≤ stage IIA (78%), invasive ductal subtype (80%), negative lymphovascular space invasion (78%), negative margin (90%), and positive ER/PR (estrogen receptor/progesterone receptor) (69%). Overall, surgical technique was not associated with differences in the proportion of patients receiving BRT (ATE: 6.0% [95% CI: -4.5 to 16.0]). There were no differences in delays to radiation treatment between the two groups (ATE: 32.8 days [95% CI: -22.1 to 87.7]). With a median follow-up time of 419 days (range: 30-793 days), there were only five recurrences, with one case of IBTR in each group. There was no difference in the ratio of CTV volume to tumor size between the two groups (p=0.38).ConclusionsOPM did not affect the decision to offer localized BRT following standard whole breast radiotherapy or significantly affect treatment times or radiation volumes. The decision to offer OPM should include a multi-disciplinary approach.

Clinicopathological features and prognosis of male breast cancer.

ObjectiveWe aimed to describe the differences in clinicopathological characteristics and overall survival (OS) between male and female breast cancer patients, and to develop a prognostic nomogram to predict survival in patients with male breast cancer (MBC).MethodsUsing the Surveillance, Epidemiology, and End Results database, we compared age, race, histological type, histological grade, tumor size, lymph node status, metastases, estrogen/progesterone receptor (ER/PR) and HER-2 status between male and female patients, and analyzed their relationships with OS. We established a nomogram and produced a calibration curve to observe its predictive effect.ResultsAge, race, T stage, N stage, bone and lung metastases, and histological type and grade differed between male and female patients. OS in male patients was related to age, tumor size, metastatic site, ER/PR status, and histological grade, but not to race or lymph node status. A nomogram was established, which showed good predictive performance for survival in MBC patients (area under the curve = 0.7).ConclusionMBC has a worse prognosis than female breast cancer, mainly characterized by late onset age, late staging, high proportion of invasive non-specific histological types, high histological grade, and luminal breast cancer.

Clinical application of gelatin sponge microparticles combined with pirarubicin for hepatic transcatheter arterial chemoembolization in breast cancer liver metastasis treatment: results of a single-center long-term study

ObjectiveTo retrospectively analyze the safety and long-term clinical efficacy of gelatin sponge microparticles combined with the chemotherapy drug pirarubicin for hepatic transcatheter arterial chemoembolization (GSMs-TACE) in order to treat breast cancer liver metastasis (BCLM).MethodsTwenty-seven BCLM patients who underwent GSMs-TACE from July 2010 to July 2016 were enrolled. Tumor target blood vessels were slowly and regionally embolized with absorbable gelatin sponge particles and pirarubicin injections. Plain computed tomography (CT) scans and biochemical indexes were re-examined at 4 days after treatment, and enhanced CT scans or magnetic resonance images and biochemical indexes, 1 month later. For patients with stable tumors, the follow-up period was 2 to 3 months, and the tumor response was evaluated using Modified Response Evaluation Criteria in Solid Tumors. Adverse reactions, survival time, and prognostic factors were assessed.ResultsBy October 2019, 27 patients with BCLM had undergone GSMs-TACE, with an average of 2.44 ± 1.58 treatments. The 1-, 3-, and 5-year survival rates were 62.96%, 22.22%, and 14.81%, respectively, and the mOS was 22.0 months. No serious complications, such as acute liver failure and liver abscess, had occurred. There were two cases of acute cholecystitis that recovered after symptomatic treatment. Multivariate analysis of the prognosis showed that the primary tumor size, number of metastatic lymph nodes, estrogen receptor/progesterone receptor (ER/PR) status, and time to postoperative liver metastasis and combination therapy were statistically significant.ConclusionsThe overall prognosis of BCLM was poor. GSMs-TACE was safe and effective for BCLM treatment and could prolong the median survival time of patients. Therefore, it is worthy of widespread clinical application.

PO-1110 Local control in hypofractionated RT after breast-conservative surgery among young Egyptian patients

Purpose or Objective Since the beginning of coronavirus disease (COVID-19), there is a compelling reason for the use of hypofractionated radiotherapy (HFRT) schedules in cancer management to safeguard the patients and the treating physicians. However, conflicting data shows that young breast cancer (BC) patients have a higher locoregional relapse after breast-conservative surgery (BCS). Given this, we aim to compare the locoregional control between conventional radiotherapy (CRT) and HFRT after BCS in a cohort of young BC patients. Materials and Methods We retrospectively reviewed stage I-III BC patients in two centers diagnosed between 2008 and 2017 who underwent BCS and had follow-up data. Patients were categorized into two groups: CRT (50Gy in 25 fractions) vs. HFRT (40.5 - 42.5 Gy in 15-16 fractions). Boost was added to all patients. Results 247 patients were included in this analysis. Among them, 87 (35%) received CRT, while 160 (65%) were treated by HFRT. The clinicopathological characteristics of CRT vs. HFRT were as follows: The majority of the patients were T1 and T2, 92% in CRT vs. 94% in HFRT. N3 was rare in both groups, 8.3% vs. 5.1% in CRT vs. HFRT, respectively. The CRT had more stage 3 patients than HFRT, 35% vs. 23% respectively, but fewer stage 1 (18.1 vs. 23.5%, respectively). Estrogen/progesterone receptor (ER/PR) positive was 79.5% vs. 76.7%, HER2 enriched was 7% vs. 5%, while high Ki-67 was 56.3% vs. 71.4% in CRT vs. HFRT, respectively. Lymphovascular invasion was positive in 52.7% of CRT vs. 64.3% in HFRT, while the extracapsular extension was positive in 31% of CRT vs. 19.4% in HFRT. The distribution of tumor grades was similar across the groups. After a median follow up of 42 months (range: 5-135), 10% of the total 247 patients developed locoregional recurrences:13.8% (n=12) were in CRT group, whereas 8.1% (n=13) in HFRT, p = 0.158;the HFRT group had insignificant lower locoregional recurrences. In univariate and multivariate analysis, only very young age was an independent poor prognostic factor for locoregional failure. Conclusion We found no significant differences in locoregional control between CRT and the HFRT following BCS among young BC patients. In this COVID-19 pandemic, HFRT should also be considered in young BC patients to shorten the treatment time.

Prognostic value of androgen receptor expression and molecular alterations in metastatic triple-negative or low hormone receptor breast carcinomas

Metastatic breast carcinomas (BCs) with phenotype of triple-negative (TNBC) or low hormonal receptor levels [estrogen receptor (ER)/progesterone receptor (PR)<10% and HER2-] are mainly treated with cytotoxic chemotherapy. Targeting androgen receptor (AR) pathway may represent a potential new therapeutic strategy in such group of BCs. We evaluated AR expression by immunohistochemistry and genetic alterations by next-generation sequencing. Among 114 metastatic BCs, 37 (32.5%) cases showed AR expression and 77 (67.5%) lacked AR expression. Statistical analysis revealed that AR expression is associated with older age, lobular carcinoma, positive ER and positive PR in primary tumors, and lymph node metastasis. Patients with AR-positive tumors had significantly longer metastatic intervals and overall survivals. In addition, AR-positive tumors had significantly higher rate of PI3CA mutation. Our results demonstrated that AR expression has prognostic value in this subgroup of metastatic BCs and tumors with AR expression had different molecular alterations compared with those without AR expression.

Combined Estrogen Receptor and Progesterone Receptor Level Can Predict Survival Outcome in Human Epidermal Growth Factor Receptor 2-positive Early Breast Cancer

BackgroundIn human epidermal growth factor receptor 2 (HER2)-positive breast cancer, emerging evidence imply that clinical behaviors differ according to hormone receptor (HR) status. However, there is no conclusion about the relevance between estrogen receptor (ER) or progesterone receptor (PR) expression and clinical outcome of HER2+ breast cancer. Our study aimed to determine the influence of different ER/PR levels on survival outcome of HER2+ early breast cancer. Patients and MethodsNine hundred and nineteen early HER2+ breast cancer patients treated between 2009 and 2016 were retrospectively reviewed and HR+/HER2+ patients were further divided based on ER level (Low/L: 1%-9%; Median/M: 10%-79%; High/H: 80%-100%) and PR level (Low/L: 0%-19%; High/H: 20%-100%) according to restricted cubic spline (RCS) smoothing curve. Disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan–Meier method and log rank test. ResultsFour hundred and forty two HR+/HER2+ and 477 HR-/HER2+ breast cancer patients were included in our study and 73.2% received target therapy (HR+ 69.7%, HR- 76.5%). While HR+/HER2+ breast cancer showed better survival than HR-/HER2+ subtype in 5-year disease free survival (DFS, 93.0% vs. 86.8%, P < .001), no significant difference was observed between DFS in ER+/PR+ and ER+/PR- subgroup (94.4% vs. 90.4%, P = .22). However, a potential correlation was found between ER/PR levels and DFS in HR+/HER2+ (P = .074) tumors. In HR+/HER2+ breast cancer, all subgroups showed DFS improvement trend versus M-ER/L-PR. In all HER2+ patients, hazard ratio of H-ER/H-PR compared with HR- subtype was 0.10 (95%CI 0.01-0.74, P = .024) in all patients and 0.14 (95%CI, 0.02-1.02, P = .053) in patients receiving anti-HER2 therapy. ConclusionER/PR expression may become a predictor of survival benefit in HER2+ early breast cancer and a higher ER/PR level might be associated with better DFS.

Molecular profiling and targeted agents in recurrent, metastatic salivary gland tumor (R/M SGT) patients (pts) treated at two academic centers.

6081 Background: Treatment selection based on actionable alterations (AAs) is an appealing strategy for pts with R/M SGT. The GEMS-001 study (NCT02069730) at Princess Margaret Cancer Centre (PM) and the Vall D´Hebron Institute of Oncology (VHIO) pre-screening program facilitate the identification of AAs for R/M SGT pts and treatment selection. Methods: We analyzed R/M SGT treated at PM and VHIO from 2015 to 2020. Clinicopathological features, molecular alterations and treatment modalities were correlated with outcomes. The primary endpoint was overall response rate (ORR) by RECIST 1.1. Clinical benefit rate (CBR) was defined by pts with partial response or stable disease ≥4 months. Clinical actionability of multigene panel testing (NGS) and immunohistochemistry (IHC) were assessed as per institutional molecular tumor boards or investigators. Pts were opportunistically matched to available therapies from each center. Results: In total 206 pts were enrolled. On IHC, HER2 overexpression was present in 9%, Androgen Receptor (AR) 33%, Estrogen/Progesterone Receptor (ER/PR) 11% and ALK overexpression 0%. On NGS, PIK3CA mutation (mut) was in 9%, NTRK fusion 6%, NOTCH1-3 mut 5%, HRAS mut 6%, ERBB2/3 alterations (alt) 4% and FGFR1-4 alt 3%. Up to 92 pts (45%) displayed at least 1 AA and 36 pts (18%) had ≥2 AAs. A total of 60 pts (29%) were matched to AAs. Of those matched, median age was 60 years (range 33-84), M:F 21:39, 95% ECOG≤1 with a median number of prior treatment lines 0 (range 0-3), and their AAs included 26 AR, 9 HER2 or ERBB2 overexpression, 9 PIK3CA mut, 3 NTRK fusion, 3 FGFR1-3 alt and 10 other AAs (2 ER/PR overexpression, 2 EGFR mut, 1 c-kit mut, 1 BAP1 mut, 1 Non-V600 BRAF mut, 1 CDKN2A mut, 1 CHEK2 mut and 1 PTCH1 mut). Overall, ORR was 27% for the matched population. See table for outcomes. Conclusions: In our cohort, almost one third of the population received therapies matched to AAs. Our results suggest that targeted therapies have promising activity in pts with R/M SGT supporting comprehensive molecular and IHC profiling in treatment determination.[Table: see text]

Breast cancer ER, PR, and HER2 expression variance by germline cancer predisposition genes.

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]

An Immunohistochemical Study of Estrogen and Progesterone Receptors in Endometrium of Women with Dysfunctional Uterine Bleeding

Abnormal Uterine Bleeding (AUB) is a common complaint that affects large numbers of women from puberty to menopause. It negatively affects health and quality of life of women affected. AUB also has an economic impact for both women and society Abnormal uterine bleeding in premenopausal women is one of the most frequent problems in gynecological practice. Although some of the cases may be due to an organic cause, over 50% of the patients undergoing hysterectomy for menorrhagia have dysfunctional uterine bleeding (DUB). To analyze the percentage and intensity of estrogen receptors (ER) and progesterone receptors (PR) in endometrium of patients with DUB. This study suggests that estrogen and progesterone receptors have an important role in etiopathogenesis of dysfunctional uterine bleeding and alteration in the morphology of endometrium such as development of endometrial hyperplasia. Women in the reproductive age who are complaining of abnormal uterine bleeding, usually have an increase in ER alpha and PR expression in their endometrium.

3D Visualization of the Dynamic Bidirectional Talk Between ER/PR and Her2 Pathways.

Background: Extensive amounts of archived formalin fixed paraffin embedded (FFPE) human tumor tissues are the ultimate resource to investigate signaling network underlying tumorigenesis in human. Yet, their usage is severely limited for lacking of suitable protein techniques. In this study, a quantitative, objective, absolute, and high throughput immunoblot method, quantitative dot blot (QDB), was explored to address this issue by investigating the putative relationship between estrogen receptor (ER)/progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2) pathways in breast cancer tumorigenesis. Methods: In this descriptive observational retrospective study, ER, PR, Her2, and Ki67 protein levels were measured absolutely and quantitatively in 852 FFPE breast cancer tissues using the QDB method. ER, PR, and Her2 levels were charted on the X, Y, and Z-axes to observe samples distribution in a 3D scatterplot. Results: A “seesaw” relationship between ER/PR and Her2 pathways was observed in ER–PR–Her2 space, characterized by the expression levels of these 3 proteins. Specimens with strong expressions of ER/PR proteins were found spreading along the ER/PR floor while those with strong Her2 expression were found wrapping around the Her2 axis. Those lacking strong expressions of all 3 proteins were found accumulating at the intersection of the ER, PR, and Her2 axes. Few specimens floated in the ER–PR–Her2 space to suggest the lack of co-expression of all 3 proteins simultaneously. Ki67 levels were found to be significantly reduced in specimens spreading in the ER–PR space. Conclusions: The unique distribution of specimens in ER–PR–Her2 space prior to any clinical intervention provided visual support of bidirectional talk between ER/PR and Her2 pathways in breast cancer specimens. Clinical interventions to suppress these 2 pathways alternatively warrant further exploration for breast cancer patients accordingly. Our study also demonstrated that the QDB method is an effective tool to analyze archived FFPE cancer specimens in biomedical research.

Is There Any Rationale for Detecting Hormone Receptor/HER2 Status with Rebiopsy Without Progression Upfront Metastatic Breast Cancer? with 2 Cases

Alteration of biomarkers is well-documented in breast cancer at locoregional recurrence or metastasis attributed to tumor heterogeneity and change in biology. There is some data about discordance between primary and metastatic sites. At the same time hormone, receptor status can change after neoadjuvant treatment and at the time of recurrence. Metastatic breast cancer without progression or recurrence after the targeted chemotherapy combination for planning maintenance therapy in Human epidermal growth factor receptor 2 (HER2) overexpression positive hormone receptors positive or triple-negative patient after chemotherapy. In guidelines, the time of rebiopsy has no exact time, if the time of biopsy is usually after the progression of the tumor. We presented cases in which we detected different hormone receptor statuses from the beginning without progression and before deciding on maintenance therapy. This subject is important for deciding therapy in the aspect of heterogeneous tumors like breast cancer. The important decision of rebiopsy time is debate. In this aspect, these two cases are important examples for these kinds of patients tumor heterogeneity in breast cancer is one of the most widely known entities. We found that two patients, one of whom was estrogen progesterone receptor negative HER2 3 (+++) at the time of diagnosis and the other who was triple negative at the time of diagnosis, had positive hormone receptors in the re-biopsies without progression. We aimed to discuss the tumor heterogeneity and timing of rebiopsy in breast cancer in the light of two cases.

Can Breast Cancer Receptor Status Predict Pain Response in Palliative Radiation for Bone Metastases?

Breast cancer receptor status is predictive for local control following adjuvant radiotherapy (RT). The impact of receptor status on the clinical response to palliative RT for metastatic disease is not known. The purpose of this study was to investigate the significance of estrogen/progesterone receptor (ER/PR) and human epidermal growth factor receptor 2 (HER2) status on the subjective response of palliative RT for patients with breast cancer bone metastases. A retrospective analysis was conducted of prospectively collected patient reported outcomes (PRO) for breast cancer patients treated with palliative RT for bone metastases from 2015 to 2017. The PRO questionnaire scored pain severity, level of function, and symptom frustration at baseline and at 4 weeks following palliative RT. Patients were identified as having at least a partial improvement in PRO (≥1 improvement in score) or complete improvement (final score = 0) or no improvement. Patient demographics, tumor characteristics, systemic treatment information, and RT characteristics were collected. Patients were divided into 4 cohorts for analysis: Luminal A (ER+, HER2-, grade I-II), Luminal B (ER+, HER2-, grade III), HER2-enriched (HER2+), and triple negative breast cancer (ER/PR-, HER2-). There were 376 breast cancer patients who underwent 464 courses of palliative RT for bone metastases. Radiotherapy included 216 multifraction courses (median dose 20Gy) and 248 single fraction courses (median dose 8Gy). The cohort comprised of: 275 patients with Luminal A, 114 with Luminal B, 46 with HER2-enriched, and 29 with triple negative disease. On multivariate analysis, triple negative breast cancer was associated with a lower rate of partial improvement (OR: 0.37, p = 0.030) and complete improvement (OR: 0.27, p = 0.037). Lower baseline score (OR:1.19, p<0.001) and multiple bone sites treated concurrently (OR: 2.33, p = 0.021) were associated with a higher rate of partial improvement. Use of multifraction RT, chemotherapy, and hormone therapy were not associated with improvement in PRO in the cohort as a whole. In a subgroup analysis of patients with triple negative breast cancer (n = 29), multifraction RT was associated with a higher rate of partial improvement PRO (OR:15.8, p = 0.022) and higher rates of partial and complete improvement in PRO pain-specific scores (OR:19.7, p = 0.012 and OR:12.9, p = 0.035, respectively). Palliative radiotherapy for breast cancer bone metastases was less effective for patients with triple negative disease, even when controlling for the use of systemic therapy and hormone therapy. In this cohort, multifraction radiotherapy was associated with higher rates of symptom relief. There may be a role for dose escalation in this cohort. Otherwise, single fraction radiotherapy was associated with similar rates of symptom relief when compared to multifraction regimens.

Tissue Microarray Detection of Estrogen Receptor, Progesterone Receptor, and C-erbB-2 in Patients with Ovarian Cancer and a Preliminary Study on the Molecular Typing of Ovarian Cancer

We evaluated the expression of estrogen receptor (ER), progesterone receptor (PR), and C-erbB-2 in patients with ovarian cancer using tissue microarrays (TMA) and preliminarily analyzed molecular typing data. Specimens from 119 ovarian cancer patients were collected and were analyzed by TMA. The expression of ER, PR, and C-erbB-2 was examined by IHC and the clinicopathological associations were analyzed. The results indicated that higher ER expression was observed in SC and EC, whereas PR exhibited a similar expression pattern, but relatively lower compared with ER expression. Conversely, very weak expression was observed in CCC and MC, especially for PR (All P &lt;0.05). C-erbB-2 exhibited no expression pattern differences among the different histological types (All P &gt;0.05), but exhibited higher positive expression in FIGO III and IV stages, whereas there was no difference in ER and PR expression among the different stages. Higher PR expression was observed in middle and highly differentiated tumors, whereas higher C-erbB-2 expression was associated with low degree of differentiation (P &lt;0.05). Patients with ER (+) PR (+) C-erbB-2 (?) had a better prognosis and patients with ER (?) PR (?) C-erbB-2 (+) had the worst prognosis. In conclusion, ER and PR tend to be highly expressed in less malignant ovarian cancer subtypes such as SC and EC. Ovarian cancer patients with ER/PR double-positive and C-erbB-2 negative expression patterns survive longer.

Hormonal Receptor Status Determines Prognostic Significance of FGFR2 in Invasive Breast Carcinoma

Simple SummaryFGFR2-ER-PR crosstalk leads to hormone-independent progression of breast cancer. In vitro, FGFR2 stimulates PR transcriptional activity and mediates resistance to anti-ER therapies. The postulated poor prognostic effect of FGFR2 overexpression has not been confirmed at clinical level. Our clinical data show that, counterintuitively, low expression of FGFR is linked to poor prognosis in breast cancer and its prognostic value is dependent on the hormonal receptor status, but not PR transcriptional activity. This shows, that the role of FGFR in breast cancer is more complex, which may explain unsatisfactory results of the clinical trials with FGFR inhibitors.Interaction between fibroblast growth factor receptor 2 (FGFR2) and estrogen/progesterone receptors (ER/PR) affects resistance to anti-ER therapies, however the prognostic value of FGFR2 in breast cancer (BCa) remains largely unexplored. We have recently showed in vitro that FGFR2-mediated signaling alters PR activity and response to anti-ER treatment. Herein, prognostic significance of FGFR2 in BCa was evaluated in relation to both ER/PR protein status and a molecular signature designed to reflect PR transcriptional activity. FGFR2 was examined in 353 BCa cases using immunohistochemistry and Nanostring-based RNA quantification. FGFR2 expression was higher in ER+PR+ and ER+PR- compared to ER−PR− cases (p < 0.001). Low FGFR2 was associated with higher grade (p < 0.001), higher Ki67 proliferation index (p < 0.001), and worse overall and disease-free survival (HR = 2.34 (95% CI: 1.26–4.34), p = 0.007 and HR = 2.22 (95% CI: 1.25–3.93), p = 0.006, respectively). The poor prognostic value of low FGFR2 was apparent in ER+PR+, but not in ER+PR− patients, and it did not depend on the expression level of PR-dependent genes. Despite the functional link between FGFR2 and ER/PR revealed by preclinical studies, the data showed a link between FGFR2 expression and poor prognosis in BCa patients.

Endometrial expression of e-cadherin in relation to estrogen-progesterone receptor characteristics of the endometrium

Aim: to evaluate the endometrial expression of e-cadherin in relation to the estrogen-progesterone-receptor status of the endometrium.Materials and methods. In total 137 women were examined including 81 patients with infertility and 40 with a history of early pregnancy loss (main group); for comparison, 16 healthy fertile women (control group) were also examined. Endometrial aspiration biopsy was performed on 6–8 days after ovulation; in parallel, a peripheral blood sample was taken to determine the levels of estradiol and progesterone. A histological and immunohistochemical study of the endometrium with determination of estrogen (ER) and progesterone (PR) receptors and e-cadherin expression was carried out.Results. All fertile women (n = 16) and only 44 % (n = 53) of patients in the main group had the normal pattern of hormonereceptor endometrial interactions, i. e., low expression of ER and PR in the endometrial glands as well as reduced expression of ER and high expression of PR in the endometrial stroma. The endometrial e-cadherin expression was assessed in the following cohorts: a) women with normal hormone-receptor interactions (16 women in the control group and 53 women in the main group); b) with abnormal variants of hormone-receptor interactions in the endometrium (68 patients in the main group). The frequency of reduced e-cadherin expression was significantly lower in the cohort of women with normal estrogenprogesterone-receptor endometrial status (a) than in the cohort of women with abnormal variants of the endometrial “response” (b): in the luminal epithelium – in 5 % (3 out of 63) (а) vs. 17 % (8 out of 47) (b) (p &lt; 0.05); in the glands – in 13 % (9 out of 69) (a) vs. 37 % (25 out of 68) (b) (p &lt; 0.05).Conclusion. The estrogen-progesterone-receptor status of the endometrium is significant for the e-cadherin expression in the luminal epithelium and glands of the endometrium.

Correlation of hormonal receptor level and survival outcome in HER2-positive nonmetastatic breast cancer.

e12568 Background: In human epidermal growth factor 2 (HER2)-positive breast cancer, emerging evidences imply that clinical behavior and prognosis differ according to hormone receptor (HR) status. However, there is no conclusion about the relevance between estrogen receptor (ER) or progesterone receptor (PR) expression and clinical outcome of HER2-positive breast cancer. Our study is designed to determine the effect of different ER/PR levels on survival benefit of HER2-positive early breast cancer. Methods: 984 non-metastatic HER2-positive breast cancer patients between January 2009 and December 2016 were retrospectively reviewed and HR+/HER2+ patients were further classified into several subgroups based on ER expression level (Low/L: 1-9%; Median/M: 10-74%; High/H: 75-100%) and PR expression level (Low/L: 0-19%; High/H: 20%-100%). Clinical features and survival outcomes were evaluated. Results: A total of 461 HR+/HER2+ and 523 HR-/HER2+ breast cancer patients were included in our study and 69.8% of them received target therapy (HR+ 67.5%, HR- 71.9%). While HR+/HER2+ breast cancer showed better survival than HR-/HER2+ subtype in 5-year disease free survival (DFS, 92.6% vs 87.6%, p = 0.002), no significant difference was observed between 5-year DFS rates in ER+/PR+ and ER+/PR- subgroup (94.3% vs 89.7%, p = 0.150). However, a possible correlation was found between ER/PR levels and DFS both in HR+/HER2+ (p = 0.057) and all HER2+ (p &lt; 0.001) breast cancer. In HR+/HER2+ breast cancer, all subgroups showed DFS improvement trend versus M-ER/L-PR patients and hazard ratio of H-ER/H-PR subtype had a statistical difference (0.36, 95%CI 0.13-0.99, p = 0.047). In all HER2+ patients, hazard ratio of H-ER/H-PR compared with HR- subtype was 0.32 (95% CI, 0.13-0.80, p = 0.015). M-ER/L-PR presented similar DFS outcome with HR- subtype in our study. Conclusions: ER/PR expression may become a predictor of survival benefit in HER2-positive non-metastatic breast cancer and a higher ER/PR expression level might be associated with better DFS.

Points to consider: is there evidence to support BRCA1/2 and other inherited breast cancer genetic testing for all breast cancer patients? A statement of the American College of Medical Genetics and Genomics (ACMG)

Points to consider: is there evidence to support BRCA1/2 and other inherited breast cancer genetic testing for all breast cancer patients? A statement of the American College of Medical Genetics and Genomics (ACMG)