Estrogen Receptor Determination Research Articles

Profiling Breast Tumor Heterogeneity and Identifying Breast Cancer Subtypes Through Tumor-Associated Immune Cell Signatures and Immuno Nano Sensors.

Breast cancer is a complex and heterogeneous disease with varying cellular, genetic, epigenetic, and molecular expressions.The detection of intratumor heterogeneity in breast cancer poses significant challenges due to its complex multifaceted characteristics, yet its identification is crucial for guiding effective treatment decisions and understanding the diseaseprogression. Currently, there exists no method capable of capturing the full extent of breast tumor heterogeneity. In this study, the aim is to identify and characterize metabolic heterogeneity in breast tumors using immune cells and an ultrafast laser-fabricated Immuno Nano Sensor.Combining spectral markers from both Natural Killer (NK)and T cells, a machine-learning approach is implemented to distinguish cancer from healthy samples, identify primary versus metastatic tumors, and determine estrogen receptor (ER)/progesterone receptor (PR) status at the single-cell level. The platform successfully distinguished heterogeneous breast cancer samples fromhealthy individuals, achieving97.8%sensitivity and92.2%specificity, andaccurately identifiedprimary tumors from metastatic tumors. Characteristic spectral signatures allow for discrimination between ER/PR-positive andnegative tumors with 97.5% sensitivity.This study demonstrates the potential of immune cell-based metabolic profiling in providing a comprehensive assessment of breast tumor heterogeneity and paving the way for minimally invasive liquid biopsy approaches in breast cancer diagnosis and management.

Synthesis Studies and the Evaluation of C6 Raloxifene Derivatives.

Methodology is described for the synthesis of C6 derivatives of raloxifene, a prescribed drug for the treatment and prevention of osteoporosis. Studies have explored the incorporation of electron-withdrawing substituents at C6 of the benzothiophene core. Efficient processes are also examined to introduce hydrogen bond donor and acceptor functionality. Raloxifene derivatives are evaluated with in vitro testing to determine estrogen receptor (ER) binding affinity and gene expression in MC3T3 cells.

PET/CT with <sup>18</sup>F-Fluoroestradiol in First Diagnosed Breast Cancer. A Pilot Study

Purpose: To evaluate the informativity of PET/CT with 18F-FES in determining estrogen receptor (ER) positivity in breast tumor tissue, as well as in regional lymph nodes or distant metastatic foci. Material and methods: The data of 30 patients who underwent PET/CT with 18F-FES performed at the stage of primary diagnosis were retrospectively analyzed. The study included patients before the start of specific treatment or on the background of neoadjuvant hormone therapy, with previously determined expression of ER according to the results of IGC. 14 patients underwent 18F-FDG PET/CT with 2–7 days difference between both PET/CT. Results: In our study, the mean SUVmax value in the primary tumor focus was 4.8, the lowest SUVmax = 1.61, and the highest SUVmax = 18.86. 18F-FES accumulation considered suspicious for metastatic lesion in axillary lymph nodes on the affected side was detected in 16 patients (56 %), mean SUVmax = 5.2, lowest SUVmax = 0.99, highest SUVmax = 11.54. On subsequent histological examination, tumor changes in axillary lymph nodes were confirmed in 16/16 patients. Conclusion: PET/CT with 18F-FES is a diagnostic method for noninvasive evaluation of ER expression in tumor foci, which can complement the data of traditional diagnostic methods and has a significant clinical potential. In our study, the results of PET/CT with 18F-FES coincided with the data of immunohistochemical study in 100 % of cases.

Concordance of RT-qPCR with immunohistochemistry and its beneficial role in breast cancer subtyping.

This study was to compare the concordance of transcription-quantitative polymerase chain reaction (RT-qPCR) with immunohistochemistry (IHC) in determining estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and tumor proliferation index (Ki67) status in breast cancer, and to assess the prognosis based on different subtypes. Totally 323 breast cancer patients were selected, including 216 in the training set and 107 in the validation set. Logistic regression models were constructed using 5-fold cross-validation with the mRNA expression of each biomarker as the predictor and the corresponding IHC expression level as the binary response variable. Receiver operating characteristic curve was used to determine the cutoff value. When the thresholds of ER, PR, HER2, and Ki67 were 0.764, 0.709, 0.161, and 0.554, there existed high concordance rates between IHC and RT-qPCR in ER (94.4%), PR (88.0%) and HER2 (89.4%) and a medium concordance rate in Ki67 (67.8%), which were further confirmed in the validation set (ER: 81.3%, PR: 78.3%, HER2: 80.4%, and Ki67: 69.1%). Based on the subtyping stratified by RT-qPCR, the 5-year recurrence-free interval rates of patients with luminal, HER2-enriched, and triple-negative subtypes were 88% (95% CI: 0.84-0.93), 82% (95% CI: 0.73-0.92) and 58% (95% CI: 0.42-0.80), respectively, which were similar to those assessed by IHC (88%, 78% and 47%). RT-qPCR may be a complementary method to IHC, which can not only provide additional useful information in clinic, but also show more advantages over IHC in determining certain subtypes of breast cancer.

Effect of Surface Decalcification With Hydrochloric Acid on the Determination of Estrogen Receptor, Progesterone Receptor, Ki67, and Human Epidermal Growth Factor Receptor 2 Expressions in Invasive Breast Carcinoma Based on Immunohistochemistry and Fluorescence In Situ Hybridization.

Bone is the most common site of metastatic breast cancer (MBC). EDTA is often used to decalcify bony tissue samples to ensure the accurate assessment of antigenicity in MBC. It takes ~24 to 48 hours to decalcify small bone tissues such as bone marrow, which is considered unacceptable given the priority that is often placed on the rapid processing of bone marrow trephine cores. Thus, an effective decalcification method that preserves genetic material is needed. We performed immunohistochemical studies on surface decalcification (SD) in breast tumors and evaluated the effect of SD on receptor status and human epidermal growth factor receptor 2 (HER2). Fluorescence in situ hybridization was performed on a subset of these tumors to establish a protocol for handling bone specimens for MBC. Forty-four cases of invasive breast tumors were studied. We compared the immunohistochemical expressions of estrogen receptor (ER), progesterone receptor (PR), Ki67, and HER2 between control tissue (nondecalcified) and parallel tissue subjected to SD with hydrochloric acid. We also evaluated the effect of SD on the fluorescence in situ hybridization expression of HER2. Categorical decreases in ER and PR expression were identified in 9/31 (29.0%) cases without SD and 10/26 (38.5%) cases with SD. HER2 expression changed from equivocal to negative in 4/12 (33.4%) cases. Among the HER2-positive cases, all remained positive after SD. The most significant declines in immunoreactivity occurred with Ki67, with an average decrease from 22% to 13%. The average HER2 copy numbers were 5.37 and 4.76 in the control and SD groups, respectively, and the average HER2/CEP17 ratios were 2.35 and 2.08, respectively. Overall, SD is an alternative decalcification method in bony metastases to assess ER, PR, and HER2 in MBC.

NOHA: A Promising Biomarker for Determining Estrogen Receptor Status Among Patients With Breast Cancer in Resource-Constrained Settings.

Challenges to breast cancer control in low-and middle-income countries exist because of constrained access to care, including pathology services. Immunohistochemistry (IHC)-based estrogen receptor (ER) analysis is limited-nonexistent because of few and inadequately staffed and equipped pathology laboratories. We have identified Nw-hydroxy-L-Arginine (NOHA) as a blood-based biomarker to distinguish ER status in US patients with breast cancer. Here, we examine NOHA's clinical utility as an ER IHC alternative in Tanzanian patients. Following informed consent, 70 newly diagnosed, known or suspected patients with breast cancer were enrolled at Kilimanjaro Christian Medical Center; basic, deidentified clinical and sociodemographic data were collected. For each, a needle prick amount of blood was collected on a Noviplex plasma card and stored at -80°C. Plasma cards and unstained tumor pathology slides were shipped regularly to US laboratories for NOHA, histologic and IHC analysis. NOHA and IHC assay operators were blinded to each other's result and patient clinical status. Paired NOHA and IHC results were compared. Slides from 43 participants were available for pathological analysis in the United States. Of those with confirmed malignancy (n = 39), 44%, 51%, 5% were ER-positive, ER-negative, and ER inconclusive, respectively. NOHA levels were available among 33 of 43 of those with pathological data and showed distinct threshold levels correlating 100% to tumor ER IHC and disease categorization where a level below 4 nM, from 4 to 8 nM, and above 8 nM signified ER-negative, ER-positive, and no cancer, respectively. The results are consistent with findings from US patients and suggest NOHA's clinical utility as an accessible IHC replacement in determining ER status among low-and middle-income country patients with breast cancer, promising to extend access to cost-efficient, available hormonal agents and improve outcomes.

Determination of estrogen receptor, progesterone receptor and epidermal growth factor receptor in canine vaginal tumors and vaginal fold prolapse: A preliminary study

Eight dogs with a vaginal mass were incorporated into the study. According to the vaginal examination (vaginoscopy, exfoliative vaginal cytology) and histopathology, the groups were designed as vaginal fold prolapse (Group VFP; n=3) and vaginal tumor (Group VT; n=5). Vaginal tissue samples were homogenized. Tissue homogenates were analyzed with enzyme-linked immunosorbent assay (ELISA) to determine the levels of estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor (EGFR). The mean ER level was significantly higher in group VT compared to the group VFP (P<0.05). However, PR and EGFR levels did not showed significance related to the groups (P>0.05). In conclusion, significant differences were obtained between the bitches with VT and VFP related to ER levels although both groups have pathological conditions. Further studies are needed to discuss these pathologies with healthy bitches in terms of steroid receptor and EGFR levels in both vaginal tissue and blood sera.

Ultrasound evaluation of ductal carcinoma in situ of the breast.

To assess the role of ultrasound (US) in detecting and characterizing ductal carcinoma in situ (DCIS) of the breast and to investigate the correlation between ultrasonographic and biological features of DCIS. In total, 171 patients (mean age 44; range 39-62) with 178 lesions were retrospectively evaluated by two independent radiologists searching for US mass or non-mass lesions. Immunohistochemistry analysis was performed to determine estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. The US detection rate and pattern distribution among the lesion types were evaluated. The χ2 test was used to evaluate the correlation between the US findings and the biological factors. Statistical significance was indicated by p values < 0.05. Inter-observer agreement was calculated by Kohen's k test. US detected 35% (63/178) of all lesions. Fifty-two (83%) lesions were classified as mass lesions, and 11 (17%) as non-mass lesions (p < 0.0001). Among the mass lesions, the most common shape was irregular (79%; p < 0.0001), with 45 (87%) lesions having indistinct margins. Hypoechogenicity was the most common echo pattern (49 cases, 94%; p < 0.0001). Microcalcifications were found in 23 cases (37%; p = 0.004) and were associated with mass lesions in 15 cases (65%) and with non-mass lesions in 8 cases (35%) (p = 0.21). An almost perfect inter-observer agreement (k = 0.87) was obtained between the two radiologists. A significant ER expression was found in mass lesions (83%; p < 0.0001), with no significant PR (p = 0.89) or HER2 expression (p = 0.81). Among the lesions with microcalcifications, only 7 out of 23 cases (30%) were positive for HER2 (p = 0.09). DCIS represents a heterogeneous pathological process with variable US appearance (mass-like, non-mass-like, or occult). The most common US finding is represented by mass-type, hypoechogenic lesions with indistinct margins. A significant ER expression exists among mass-type lesions, while microcalcifications seem not to be associated with HER2 expression.

Evaluating the estrogenicity of an effluent-dominated river in California, USA: Comparisons of in vitro and in vivo bioassays

Estrogenically active compounds (EACs) in surface waters can disrupt the endocrine system of biota, raising concern for aquatic species. Concentrations of EACs are generally higher in effluent-dominated aquatic systems, such as California's Santa Ana River (SAR). Addressing estrogenicity of effluent-dominated waters is increasingly important due to both increasing urbanization and climate change. To this end, water samples were collected from multiple sites downstream of wastewater treatment plants (WWTPs) and intermittent points along the SAR during 2018–2019 and cell-based bioassays were used to determine estrogen receptor activity. During baseflow conditions, the highest estradiol equivalencies (EEQs) from all SAR water between summer (August and September) and fall (November) sampling events in 2018 were from Yorba Linda (EEQ = 1.36 ± 0.38 ng/L) and Prado (1.14 ± 0.13 ng/L), respectively. Water extracts in January 2019 following a major rainfall generally had higher EEQs with the highest EEQ of 10.0 ± 0.69 ng/L observed at Yorba Linda. During low flow conditions in November 2018, male Japanese medaka (Oryzias latipes) fish were exposed to SAR water to compare to cell bioassay responses and targeted analytical chemistry for 5 steroidal estrogens. Chemical-based EEQ correlations with in vitro EEQs were statistically significant. However, vitellogenin (vtg) mRNA expression in the livers of medaka exposed to SAR water was not significantly different compared to controls. These results indicate that seasonal variation and surface water runoff events influence estrogenic activity in the SAR and may induce estrogenic effects to native fish populations in wastewater-dominated streams in general.

Clinico-pathological study of locally advanced breast cancer and their hormone receptor analysis

Background: Breast carcinoma is one of the most common malignant tumor of women. Determination of estrogen receptors (ER) and progesterone receptors (PR) status, prior to therapeutic intervention has become standard practice. Survival and response to hormone therapy are most favorable among women who are receptor positive. The aim of this study is to assess the hormone receptor status in locally advanced breast carcinomas and correlate this reactivity pattern with tumor stage, clinical stage and lymph node metastasis. Objective of the study was to co-relate the locally advanced breast cancer and their hormone receptor analysis.Methods: Patients who visited Department of General Surgery, Hamidia Hospital, Bhopal were assessed clinically, radiologically and histopathologically and then ER and PR study was done, for a total of 50 cases were done.Results: In our study majority of the cases were locally advanced breast cancer (50%) which may be due to the low socio economic status, late presentation, pain tolerance, illiteracy and availability of the resources. Majority of cases were in postmenopausal, clinical stage 3 and histological grade 2. ER positivity 50% and PR positivity 44% and it was found that hormone receptor positivity was high in locally advanced breast cancers 63.5%.Conclusions: Hormone receptor analysis should be an integral part of initial workup of carcinoma breast, as the percentage of hormone receptor positivity is increasing in our population in locally advanced breast cancer. So locally advanced breast cancer can be diagnosed at an early stage by screening and conducting breast awareness programs.

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.

Association between the methylation status of PCDH17 and the efficacy of neoadjuvant chemotherapy in triple-negative breast cancer.

The present study aimed to assess whether the methylation status of the protocadherin 17 gene (PCDH17) in triple-negative breast cancer (TNBC) tissues was associated with the efficacy of neoadjuvant chemotherapy (NAC). The present study included 280 patients diagnosed with TNBC using core needle biopsy. Tumor pathological diagnosis was determined via hematoxylin and eosin staining. Immunohistochemical staining was used to determine estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2 and Ki-67 status. PCDH17 methylation status was analyzed using methylation-specific PCR. χ2 tests were performed to analyze differences between PCDH17 methylation status and TNBC clinicopathological features. Univariate and multivariate logistic regressions were used to analyze whether PCDH17 methylation status predicted a curative effect of NAC. The multivariate analysis included factors with P<0.2 from the univariate analysis and those that were clinically associated with NAC. A total of 228 patients were positive for PCDH17 methylation, while the remainder 52 were negative. Additionally, 107 patients achieved pathological complete response (pCR) after NAC. The pCR rate was 67.3% among the 52 patients negative for PCDH17 methylation and 31.6% among the 228 patients positive for PCDH17 methylation. Patients who were negative for PCDH17 methylation and had high Ki67 expression exhibited significantly higher pCR rates than their counterparts. The present results demonstrate that PCDH17 methylation status may predict the response to NAC in patients with TNBC. Therefore, this epigenetic characteristic may serve as an indicator of treatment efficacy.

Prognosis and endocrine therapy selection for patients with low hormone receptor-positive breast cancer following neoadjuvant chemotherapy: A retrospective study of 570 patients in China.

The 2010 American Society of Clinical Oncology guidelines have reduced the immunohistochemistry cut-off value for determining estrogen receptor b positivity from 10 to 1% of stained cells in breast cancer. In clinical practice, low-hormone receptor positive (low HR+) tumors are classified in the luminal subtype, although they exhibit aggressive features and poor prognosis. Information regarding the prognosis of patients with breast cancer following treatment with optimal endocrine therapy and neoadjuvant chemotherapy (NAC) is currently lacking. In the present study, the differences in clinical characteristics and survival of patients with breast cancer were compared among those with low and high HR+ breast cancer who received NAC. Furthermore, the effects of different types of endocrine therapies on the prognosis of patients with breast cancer were compared. The study population comprised patients with primary breast cancer who were treated at the Zhejiang Cancer Hospital between January, 2007 and December, 2017. Patients were divided into three groups based on the results of immunohistochemistry: HR+ (positive staining >10%), HR- (positive staining <1%) and low HR+ (positive staining 1–10%). The low HR+ group was further divided into three subgroups according to the different endocrine therapies administered: Tamoxifen, aromatase inhibitor or no treatment. Among the 570 patients included in the present study, 60 (10.53%) patients had low HR+ tumors. With a median follow-up of 48.98 months, patients with low HR+ tumors had reduced survival rates compared with those with HR+ tumors. Furthermore, the pathologic complete response rate (pCR) of patients with low HR+ was comprised between pCR from patients with HR+ and pCR from patients with HR- following NAC treatment. In addition, no significant difference in the overall prognosis was observed among patients with low HR+ following treatment with different endocrine therapies. Subsequently, patients in the low HR+ group were more likely to benefit from NAC compared with patients in the HR+ group. Intensive endocrine therapy may therefore improve the prognosis of patients with breast cancer and low HR+; however, further investigation is required.

Abstract P2-08-06: Standardized nCounter-based determination of estrogen receptor (ER), progesterone receptor (PR) and HER2 receptor status in breast cancer

Abstract Background: The expression of ER, PR and HER2 in breast cancer is determined by routine pathology assessment to indicate systemic treatment. Here, we investigated the ability of a standardized mRNA-based assay to predict ER, PR and HER2 status and treatment response. Methods: ESR1, PGR and ERBB2 expression was analyzed from the standardized nCounter-based PAM50 assay in 1,544 FFPE breast tumors obtained from 13 independent studies (NeoEribulin, GEICAM 2012-09, TBCRC023/006, LPT109096, EGF117165, PAMELA, PerELISA, GEICAM 2003-11, VENTANA, IBIMA and HCB). All immunohistochemical and in situ hybridization analyses followed ASCO/CAP criteria and were performed in central labs except for Neoeribulin and VENTANA studies. To explore the best cutoff for each gene, we used Monte Carlo cross validation (repeated 1000 times, 2/3 training, 1/3 testing) to achieve the highest kappa values when gene expression was compared to pathology assessment. Receiver operating characteristic analysis and area under the ROC curve (AUC) was used to evaluate the performance of each gene to predict ER, PR and HER2 status. Finally, the association of each gene (using the pre-established cutoffs) with pathological complete response (pCR) was evaluated using univariate logistic regression analyses in 2 neoadjuvant cohorts: 1) A combined HER2+ cohort using 191 tumor samples from PAMELA/PerELISA phase II trials, where patients received neoadjuvant dual HER2 blockade without chemotherapy for 15-18 weeks and 2) a combined cohort of hormone receptor-positive/HER2-negative using 205 tumor samples from IBIMA/HCB consecutive series, where patients received anthracycline/taxane-based chemotherapy. Results: Concordance between ESR1 and ER was 95.3% (95% confidence interval [95CI] 94.0-96.4%; AUC=0.98). ER+ and ER- cases were classified as ESR1- and ESR1+ in 5.5% and 4.8% of the cases, respectively. Concordance between PR and PGR was 85.2% (95CI 83.1-87.1%; AUC=0.95), and between ERBB2 and HER2 was 92.8% (95CI 91.4-94.1%; AUC=0.95). HER2+ and HER2- cases were classified ERBB2- and ERBB2+ in 16.7% and 2.9% of the cases, respectively. In the neoadjuvant HER2+ cohort, the pCR rates were 44.6% in ESR1- and 18.8% in ESR1+ (odds ratio [OR] 3.9; 95CI 1.9-8.4; p&amp;lt;0.001), 38.5 in PGR- and 15.8% in PGR+ (OR 3.2; 95CI 1.6-6.7; p=0.001), 2.6% in ERBB2- and 35.3% in ERBB2+ (OR 19.7; 95CI 2.6-149.1; p&amp;lt;0.001). In the neoadjuvant HR+/HER2- cohort, the pCR rates were 40% in ESR1- and 5.12% in ESR1+ (OR 11.5; 95IC 2.7-48.5; p&amp;lt;0.001), 15.5% in PGR- and 4.3% in PGR+ (OR 3.8; 95IC 1.3-11.7; p=0.019), 7.36% in ERBB2- and 0% in ERBB2+ (OR NA). Finally, ESR1, PGR and ERBB2 expression as continuous variables were found significantly associated with pCR in both cohorts. Conclusion: ESR1, PGR and ERBB2 standardized mRNA levels show high concordance with ER, PR and HER2, and might provide a more objective and quantitative prediction of response to chemotherapy and anti-HER2 therapy. The level of concordance between GE and pathology-based assessments is similar to 2 FDA 510(k) cleared pathology-based ER assays (e.g. SP1 versus 6F11 antibody clones), local versus central HER2 testing, and ER or PR status when determined by the ligand-binding assay versus immunohistochemistry. Citation Format: Pascual T, Tsai YS, Martín M, Lluch A, Cortes J, Llombart A, Conte P, Guarneri V, Rimawi MF, Alba E, Ruiz-Borrego M, Rojo F, de la Haba J, Schiff R, Adamo B, Vidal M, Paré L, Chic N, Muñoz M, Galvan P, Gonzalez-Farre B, Brauer HA, Sullivan A, Nuciforo P, Parker JS, Prat A. Standardized nCounter-based determination of estrogen receptor (ER), progesterone receptor (PR) and HER2 receptor status in breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-06.

ESTROGEN RECEPTORS

Objectives: Purpose of study is to determine Estrogen receptor status ininflammatory and neoplastic lesions of human gallbladder and to determine any relation ofER status with age, sex and histological grades of gallbladder carcinoma. Study Design:Retrospective observational study. Setting: Pathology Department Nishtar Medical CollegeMultan. Period: March 2016 to March 2017. Methodology: In this study total no. of 50 cases ofdifferent gallbladder diseases were included. Out of these 50 cases 30 were of neoplastic lesionsand other 20 were of non-neoplastic inflammatory lesions of gallbladder. The gallbladdersslides of these 50 cases were randomly selected from the records of Pathology Department.Demographic variables like age and gender were calculated and analyzed. Estrogen positivitywas the outcome variable of this study. Data was analyzed using computer software SPSSversion 23. Chi square Test was applied to check the association between different variables.Results: In this study, 100% (n=50) diagnosed cases of human gallbladder diseases includinginflammatory and neoplastic lesions were subjected to immunohistochemical staining for ERexpression. 100% (n=20) cases of inflammatory lesions and 100% (n=30) cases of neoplasticlesions were included, in this study. Estrogen positivity was noted in 36.7% (n=11) cases ofneoplastic lesions, while it was 25% (n=5) in inflammatory lesions cases. No association wasfound between estrogen positivity in groups, (÷2=0.751, p=0.386). (Table1).Histological typesof gallbladder carcinoma was noted as adenocarcinomas (well differentiated) in 60% (n=18)cases, adenocarcinomas (moderately differentiated) in 16.7% (n=5) cases, adenocarcinomas(poorly differentiated) in 13.4% (n=4) cases, mucinous adenocarcinomas in 1% (n=3.3) cases,adenosquamus carcinoma in 1% (n=3.3) cases and squamous cell carcinoma in 1% (n=3.3)cases. (Table2).No association was found between gender (p=0.780), stratified age (p=868)and estrogen positivity (p=0.386), after applying the chi-square. Conclusion: In this study itwas concluded that statistically no significant difference has been found between ER positivitywith age, gender and histological type of carcinoma. Presence of ER raises questions regardingthe role of estrogen in various gallbladder diseases and whether this hormone is functional ornot in neoplastic lesions is also questionable. Techniques more modified may be tried in searchof better and more reliable results. It is therefore too early to consider anti-estrogen trials ingallbladder carcinoma until the role of these steroid binding proteins is well characterized.

Retraction Note to: Extranuclear ER\u03b1 is associated with regression of T47D PKC\u03b1-overexpressing, tamoxifen-resistant breast cancer

Prior to the introduction of tamoxifen, high dose estradiol was used to treat breast cancer patients with similar efficacy as tamoxifen, albeit with some undesirable side effects. There is renewed interest to utilize estradiol to treat endocrine resistant breast cancers, especially since findings from several preclinical models and clinical trials indicate that estradiol may be a rational second-line therapy in patients exhibiting resistance to tamoxifen and/or aromatase inhibitors. We and others reported that breast cancer patients bearing protein kinase C alpha (PKCα)- expressing tumors exhibit endocrine resistance and tumor aggressiveness. Our T47D:A18/PKCα preclinical model is tamoxifen-resistant, hormone-independent, yet is inhibited by 17β-estradiol (E2) in vivo. We previously reported that E2-induced T47D:A18/PKCα tumor regression requires extranuclear ERα and interaction with the extracellular matrix. T47D:A18/PKCα cells were grown in vitro using two-dimensional (2D) cell culture, three-dimensional (3D) Matrigel and in vivo by establishing xenografts in athymic mice. Immunofluoresence confocal microscopy and co-localization were applied to determine estrogen receptor alpha (ERα) subcellular localization. Co-immunoprecipitation and western blot were used to examine interaction of ERα with caveolin-1. We report that although T47D:A18/PKCα cells are cross-resistant to raloxifene in cell culture and in Matrigel, raloxifene induces regression of tamoxifen-resistant tumors. ERα rapidly translocates to extranuclear sites during T47D:A18/PKCα tumor regression in response to both raloxifene and E2, whereas ERα is primarily localized in the nucleus in proliferating tumors. E2 treatment induced complete tumor regression whereas cessation of raloxifene treatment resulted in tumor regrowth accompanied by re-localization of ERα to the nucleus. T47D:A18/neo tumors that do not overexpress PKCα maintain ERα in the nucleus during tamoxifen-mediated regression. An association between ERα and caveolin-1 increases in tumors regressing in response to E2. Extranuclear ERα plays a role in the regression of PKCα-overexpressing tamoxifen-resistant tumors. These studies underline the unique role of extranuclear ERα in E2- and raloxifene-induced tumor regression that may have implications for treatment of endocrine-resistant PKCα-expressing tumors encountered in the clinic.

Abstract 4998: Breast tumor FOXA1 protein expression and reproductive characteristics among African-American and European-American women

Abstract Background: Forkhead box protein A1 (FOXA1) plays a key role in determining estrogen receptor (ER) function and mammary ductal development and may repress the basal cell phenotype during differentiation of breast epithelium. While reproductive factors are known to influence breast cancer risk depending on the subtypes, data on the association of tumor FOXA1 protein expression and reproductive characteristics are very limited. Methods: Tissue microarrays comprising surgical tumors from 638 women (466 African-American [AA] and 172 European-American [EA], aged 20-75 years) with primary breast cancer in the Women’s Circle of Health Study (WCHS) were analyzed for FOXA1 expression by immunohistochemistry and automated image analysis. In-person interviews were conducted to obtain data on demographics, medical and family histories, and reproductive and menstrual histories. Logistic regression was performed for FOXA1 positivity (&amp;gt;10% cells with strong staining) with menopausal status, age at menarche, age at first live birth, parity, and breastfeeding, adjusting for age at diagnosis, family history of breast cancer, and history of benign breast disease. Results: FOXA1 expression was higher in tumors from EA compared to those from AA women (80% vs. 70% positivity, P=0.011). FOXA1 expression was highly correlated with ER positivity (88% positive in ER+ and 26% in ER- breast cancer among AA women; 90% and 29% respectively among EA women; both P&amp;lt;0.001). Among AA women, a higher number of live births was associated with lower FOXA1 expression (odds ratio [OR]=0.45, 95% confidence interval [CI]=0.22-0.91 for 2 live births and OR=0.44, 95% CI=0.20-0.91 for ≥3 live births, versus nulliparous). However, the inverse association was not observed among EA women, potentially due to the small sample size. Conclusion: In AA women, a higher number of live births, which has been related to greater risk of ER- breast cancer, is associated with lower FOXA1 expression. Because FOXA1 promotes luminal and represses the basal differentiation, respectively, the effects of parity on expression of FOXA1 may be the link whereby it increases risk of ER- breast cancer. (Funding: NIH P01CA151135, R01CA100598, R01CA185623, P30CA072720, K07CA201334; US Army Medical Research and Material Command DAMD-17-01-1-0334; the Breast Cancer Research Foundation; and the Philip L. Hubbell family) Citation Format: Ting-Yuan David Cheng, Rochelle Payne Ondracek, Song Yao, Wiam Bshara, Thaer Khoury, Gary R. Zirpoli, Warren Davis, Elisa V. Bandera, Michael Higgins, Christine B. Ambrosone. Breast tumor FOXA1 protein expression and reproductive characteristics among African-American and European-American women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4998. doi:10.1158/1538-7445.AM2017-4998

Study on Estrogen Receptor, Progesterone Receptor and HER-2/ neu Expression Pattern by Immunohistochemistry in 87 cases of Invasive Breast Cancer

Background: Now a day's determination of estrogen receptor (ER), progesterone receptor (PR) and HER-2/neu expression pattern by immunohistochemistry in invasive breast cancer have become the standard procedure for breast cancer management.Objective: To see the expression pattern of estrogen receptor, progesterone receptor and HER-2/neu in Bangladeshi women with invasive breast carcinoma.Method: This cross sectional study was performed in 87 cases of invasive breast cancer. Estrogen receptor (ER), Progesterone receptor (PR) and HER-2/neu expression pattern were assessed by immunohistochemistry using monoclonal antibodies for detecting estrogen and progesterone receptors, and polyclonal antibody for detecting HER-2/neu.Results: All the cases were graded according to Bloom-Richardson grading system. Of those, Grade I tumour was 18 (20.69%), Grade II tumour was 58 (66.67%) and Grade III tumour was 11(12.64%). Both ER and PR positive reactivity were same and it was found 65 (74.71%) and HER-2/neu reactivity pattern were found negative in 59 (67.82%) cases and positive in 28 (32.18%) cases. A statistically significant correlation was found between the expression of ER and low grade tumour (p=0.011) and combined estrogen and progesterone receptor positive reactivity with low grade tumour (p=0.002).Conclusion: ER, PR and HER-2/neu expression do not correlated with each other, so it is recommended that each test should be independently determined by immunohistochemistry in all cases of invasive breast cancer. All equivocal cases of HER-2/neu (score 2+) should be analyzed by FISH technique to find out the percentage of real score.KYAMC Journal Vol. 5, No.-1, Jul 2014, Page 436-443

Abstract P6-07-19: An alteration of hormonal receptor status throughout tumor progression related to prognosis in breast cancer patients

Abstract Purpose We aimed to identify whether hormonal receptors change throughout tumor progression, because this may influence management and influence prognosis in breast cancer patients. Patients and Methods From the institution's database, we collected data of 963 patients who developed relapse during their follow-ups. To determine estrogen receptor(ER) and progesterone receptor (PR), we retrospectively reviewed immunohistochemical(IHC) results in both primary and relapsed tumors. Results Among a total of 963 patients, 280 and 683 patients experienced locoregional relapse only and distant metastasis irrespective of locoreginal relapse, respectively. ER in 650 patients and PR in 590 patients from both primary tumor and relapse were identified, revealing a change in 157 (24.2%) and 154 (26.1%) patients, respectively. In patients with distant metastasis, assessment of ER and PR showed an alteration in 86 and 56 patients, respectively. The overall survival related to the change of ER and PR status in primary tumor and relapse was significantly different (log rank, P&amp;lt;0.001 in both ER and PR status). In addition, women with hormone receptors negative primary tumors that changed to hormone receptors positive tumors who received anti-hormonal therapy after relapse showed a statistically significant good overall survival (p&amp;lt;0.001) compared with women who had constant ER-negative tumors.(cox regression, hazard ratio 2.32 ; 95% CI, 1.91 to 3.01) Conclusion The breast cancer showed alterations of hormone receptor status throughout tumor progression, hat were related to the strategy of treatment and significantly influences survival. Therefore, investigations of hormone receptor at relapse are essential and helpful in breast cancer patient management. Citation Format: Lee E-S, Kim J, Yoo T-K, Kim Y, Han J, Kang YJ, Choi J, Rhu J, Lee H-B, Han W, Noh D-Y, Moon H-G. An alteration of hormonal receptor status throughout tumor progression related to prognosis in breast cancer patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-07-19.

Immunohistochemical determination of estrogen and progesterone receptors in breast cancer: relationship with clinicopathologic factors in 302 patients in Ivory Coast

BackgroundBreast cancer is a heterogeneous and a hormone-dependent disease. The detection of the estrogen receptor (ER) and progesterone receptor (PgR) is crucial for prognostic evaluation and treatment choice of breast cancer for clinical practice. The purpose of this study was to evaluate the expression of the hormonal receptors, their distribution, and their correlation with clinicopathologic prognostic parameters for the improvement of the patients’ treatment in Ivory Coast.MethodsThe 20-month prospective study included 302 patients who were diagnosed with primary invasive breast carcinomas at the Central Laboratory in Abidjan. The paraffin-embedded blocks of these patients were examined by immunohistochemistry to assess the ER and PgR status. The one-way analysis of variance and Chi-Square Test were used to analyze the data.ResultsThe mean age of patients at diagnosis was 48 ± 11 years. The majority of the women were premenopausal in 180 cases (59.9%). The predominant histologic type was invasive ductal carcinoma not otherwise specified (IDC NOS) in 247 cases (82%). Tumor grade 2 was more frequent in 166 cases (55%). Among 302 patients, 169 (56%) and 154 (49%) expressed ER and PgR respectively. The ER+PgR+ group with 131 cases (43%) was predominant, followed by 116 cases (38%) of ER-PgR-. The expression of ER and PgR was correlated with the age of the patients (p = 0.026) and the tumor grade (p = 0.0004). However, there was not statistically significant correlation between ER/PgR and the menopausal status of patients (p = 0.149), nor between ER/PgR and the histologic type (p = 0.523).ConclusionThe ER+PgR+ and ER-PgR- are the most common subgroups in women with breast cancer in Ivory Coast. The hormonal receptor status is associated with the age and the histologic grade in breast cancer patients. The systematic use of hormonal treatment should be reevaluated. A further study should be done to investigate the reasons of high rate of ER-PgR- in breast cancer patients in Ivory Coast.