PR Positivity Research Articles

Predicting nodal positivity in women with hormone receptor-positive (HR+), early stage breast cancer (ESBC).

574 Background: Omission of axillary surgery is appropriate in some patients with clinically node-negative (cN0), HR+ ESBC; however, there are no pre-operative tools to predict pathologic node positivity (pN+) in these women. We propose a clinically validated predictive model to inform treatment decisions regarding axillary evaluation. Methods: We constructed a cohort of adult women with ESBC (clinical T1/T2, N0, M0) diagnosed 2012-2016, who underwent lumpectomy or mastectomy and lymph node surgery without neoadjuvant therapy using the National Cancer Database breast cancer dataset. The dataset was non-randomly split into training (2012-2015) and testing (2016) for development and validation. Stepwise logistic regression was used to identify predictors of pathologic node positivity (pN0 vs pN+) in the training dataset. Potential predictors included: age, race, ethnicity, comorbidity score, histologic type, clinical T, ER positivity, PR positivity, HER2 positivity, and grade. Predictor variables required a bivariate p-value <0.30 to be entered into model, and an adjusted p-value <0.35 to stay in model. A partial score method was used to develop a lymph node prediction score (LNPS) by assigning a weighted value to each strong predictor variable (OR >1.5) and adding together the values for each included variable. LNPS was treated as a linear variable for prediction in validation dataset. Results: 423,068 women were included (2012-2015: 334,778; 2016: 88,290). Pathologic node positivity was 17% in 2012-2015 and 2016. All variables were included in the final stepwise model. Strong predictors were age, histologic type, clinical T, and grade. Scores ranged from 0-11. In the validation dataset, predicted pN+ by LNPS was very similar to actual pN+ (Table). A 1-point increase in LNPS was associated with a 3.3% increase in absolute risk of pN+. Conclusions: A novel lymph node prediction score can be used in HR+ cT1-T2 cN0 breast cancers to estimate the probability of pN+ and guide decisions regarding axillary surgical evaluation. [Table: see text]

Statistical machine learning model to predict Oncotype DX risk category in women over age 50.

524 Background: The 21-gene Oncotype DX Breast Recurrence Score multigene assay (RS) identifies women with ER positive, HER negative, axillary node-negative breast cancer (BC) for whom chemotherapy provides no invasive disease-free survival benefit compared to endocrine therapy alone. International adoption of RS testing is limited by cost and resource availability. We created a supervised statistical machine learning model using standard clinicopathologic data to predict RS risk category in women > 50 years old. Methods: From 2012 to 2018, women with ER positive, HER2 negative, pathologically node-negative BC of all ages were retrospectively identified from a prospective institutional database. Standard clinicopathologic data and RS were collected. Per institutional protocol, RS are ordered for all early-stage, ER positive tumors > 5 mm. Data were randomly split into training (n=3755) and validation sets (n=1609). A random forest model with 500 trees was developed on the training set, then evaluated on the validation set. Model predictors included age, tumor size, histologic subtype, hormone receptor status, lymphovascular invasion, and overall grade. The model was used to predict RS category (low risk: RS ≤ 25, high risk: RS > 25) in women > 50 years old. Results: 5364 unique tumors in 5189 women were identified. 3731 (70%) of tumors were identified in women > 50 years; median age was 63 years (IQR 57-69). In women > 50, median tumor size was 12 mm (IQR 9-17). Most tumors were invasive ductal (79%), low or intermediate grade (79%), and LVI was absent in 82% of tumors. Median ER staining by IHC was 95%; 28% of tumors had negative or weakly positive PR staining (1-20%). The model correctly classified 96.8% of patients as low risk (95% CI: 95.7-97.7). Negative predictive value for identifying low risk category was also high (92.3%, 90.7-93.6). Sensitivity for identifying high-risk women was 44.7% (37.4-52.1) and positive predictive value was 67.2% (58.2-75.3). A classification table on the validation set includes tumors with complete data available, including predictors and RS. Conclusions: Our model was highly specific (96.8%) for identifying women > 50 with RS ≤ 25 who do not benefit from adjuvant chemotherapy. This model may be utilized in lieu of RS testing if cost and availability are prohibitive. True RS > 25 was not as well predicted. The model will be refined following pathologic review of discordant cases to reduce false negatives. [Table: see text]

The Expression and Prognostic Significance of Claudin-8 and Androgen Receptor in Breast Cancer.

PurposeClaudin-8 (CLDN8) has been identified as an androgen-regulated gene in prostate cancer. However, the role of CLDN8 has not been fully explored in breast cancer. We aimed to explore the expression of CLDN8 and androgen receptor (AR), determine the correlation between CLDN8 and AR, assess the prognostic value of CLDN8 and AR co-expression, and investigate the possible CLDN8 expression molecular mechanism in breast cancer.Materials and MethodsTwenty-eight pairs of fresh tumor tissues and adjacent noncancerous tissues were evaluated by Western blot for CLDN8. Then, 142 breast cancer samples were determined by immunohistochemistry for CLDN8 and AR. The association of clinicopathological features with CLDN8, AR and CLDN8, and AR co-expression was examined. The Cancer Genome Atlas (TCGA) was used to demonstrate the expression of CLDN8 and correlation between CLDN8 and AR. Kaplan–Meier survival analysis was performed to assess the prognostic impact of CLDN8 and AR co-expression. The mechanisms related to CLDN8 expression in breast cancer were explored by Gene Set Enrichment Analysis (GSEA).ResultsCLDN8 was downregulated in breast cancer tissues and positively correlated with none lymph node metastasis (P=0.016), low histological grade (P=0.006), positive ER (P=0.014), positive PR (P=0.003), low Ki-67 index (P=0.017) and molecular subtypes (P=0.012). CLDN8 level was significantly associated with AR level (r=0.348; P<0.001). CLDN8 and AR co-expression was positively correlated with none lymph node metastasis (P=0.007), low histological grade (P=0.017), positive ER (P=0.019), positive PR (P=0.015) and low Ki-67 index group (P=0.038). CLDN8 and AR co-expression had a better clinical prognosis.ConclusionThe expression of CLDN8 is directly related to the expression of AR. CLDN8 and AR co-expression might be a potential prognostic evaluation factor for breast cancer patients.

Treatment Options and Follow-Up among Iraqi Patients with Breast Carcinoma

Breast cancer ranks the first among the Iraqi population and the leading cause of cancer related female mortality. In addition to the barriers that impede early detection of that cancer other major challenges include the capacity for effective multimodality treatment. Aim: To review and follow up a sample of Iraqi female patients diagnosed with breast cancer in a main referral center; recording their clinico-pathological characteristics, the offered treatment options and the rate of recurrence. Material and Methods: This retrospective study analyzed the clinical and pathological characteristics of 230 Iraqi female patients histologically diagnosed with breast carcinoma who had reliable valid data related to their demographic, clinical and tumor pathological status. The studied parameters included the age of the patient, marital status, parity, age at first delivery, occupation, history of lactation and hormonal intake, family history of breast and any other cancer, histological type, tumor grade and clinical stage. Hormone receptors (Estrogen and Progesterone) and HER2 over expression contents of the primary tumors were evaluated immunohistochemically. The offered treatment options included surgery, chemotherapy, radiotherapy, hormonal and biological targeted therapy. The rate of recurrence was evaluated after a follow-up period of three years. Results: Only 3.5% of the patients were under the age of 30 years while 39.1% were aged 50 years and over. About 84% were married, 11.3% were nulliparous, 24.9% had their first delivery before the age of 20 years and 56.9% were housewives. History of lactation was reported in 60.4%, whereas history of breast cancer was registered in 17.4%. The most common histological type of breast carcinoma was the infiltrative ductal (86.5%), well differentiated carcinomas were diagnosed in only 5.2%. The rates of positive ER, PR and HER2 tumor contents were 68.3%, 65.7% and 29.6% respectively. Overall 8.3%, 4.3%, 39.6% and 7.8% of the patients were diagnosed at stages I, II, III and IV respectively. Surgery was the primary treatment modality prescribed to the vast majority (96.1%) of the patients; 88.2% of those underwent modified radical mastectomy and only 3.6% had breast conservative surgery. Whereas 91.7% received chemotherapy, radiotherapy, hormonal and biological therapy were applied on 65.7%, 63.5% and 27.4% respectively. Recurrence of breast carcinoma three years following treatment was displayed among 9.7%; displaying significant direct association with the clinical stages of the disease (p&lt;.05). Conclusions: Breast cancer is still diagnosed at relatively advanced stages at the time of first presentation in Iraq; requesting radical mastectomy. Early detection represents the principal approach to control breast cancer in the near future. Regular long-term follow up through multidisciplinary tumor boards is mandatory to monitor response to therapy and recurrence.

Abstract P1-10-26: Gene expression levels of DTX3, CACNA1G, IL11, ETV4 and TSPAN7 selected by LASSO penalty regression could predict pCR after neoadjuvant chemotherapy in breast cancer tumors

Abstract Introduction: While pCR has been amply associated with improved treatment outcome in patients treated with NAC and surgery, there are only few studies that explore the molecular determinants of pCR. Given the discrete percentage of patients who achieve pCR after NAC, it is of upmost need to identify biomarkers that can discern between responder and non-responder patients before NAC and therefore determine the best therapeutic approach in advance. Our aim is to find the best combination of variables to predict pCR in our cohort. Patients: To evaluate if there is a gene expression profile that could predict pathological complete response (pCR) to NAC, we selected a cohort of 69 patients treated with neoadjuvant chemotherapy consisting of anthracyclines + taxanes; HER2+ patients were further treated with trastuzumab. The median age was 48 years, and 71% of patients were premenopausal. The median of mammographic tumor size was 3,7. Most patients (89%) had invasive ductal carcinoma, and the histological grade was mainly 2 (55,7% Grade 1+2; 44,3% Grade 3). ER and PR positivity were seen in 63% and 53% of cases respectively. HER2 overexpression was seen in 20% of tumors. Methods: Gene expression was evaluated in 770 genes involved in 13 canonical cancer pathways as screened with the nCounter® PanCancer Pathways panel in FFPE pre-treatment tumor biopsies and analyzed with the nSolverTM software. The collected clinical and pathologic variables were age, mammographic tumor size, nodal status, tumor grade, HR status, HER2-overexpression, Ki67 percentage, IHQ subtype and PAM50 subtype. Finally, LASSO regression was used to predict pCR based on normalized gene expression levels and clinical and pathological data. Results: Out of the 69 enrolled patients, 27 achieved pCR (39%) and 42 did not (determined by Miller and Payne criteria). High-quality RNA was isolated from each patient for doing Nanostring nCounter experiment. Based on the gene expression levels of the PanCancer Pathways panel, Lasso regression identified a subset of genes as predictive of pCR. Therefore, the combination of expression levels of DTX3, CACNA1G, IL11, ETV4 and TSPAN7 genes, predicted pCR with an average 70% of Area Under the Curve ROC (AUC) on the test set in a cross-validation scheme. DTX3 is a member of Notch pathway, IL11 from JAK-STAT pathway, CACNA1G from MAPK pathway, ETV4 and TSPAN7 from Transcriptional misregulation pathway. DTX3, CACNA1G and TSPAN7 are down-regulated and IL11 and ETV4 are up-regulated in patients who achieved pCR. Regarding the clinical and pathological data, the best model for predict pCR obtained an 60% of AUC and the selected variables were age, mammographic tumor size, nodal status, tumor grade and Ki67 percentage. Conclusions: In our cohort, the combination of gene expression levels of DTX3, CACNA1G, IL11, ETV4 and TSPAN7 can predict tumor response to NAC even better than any clinical or pathological variable. Although validation in a separate cohort is necessary, our results indicate that this combination could constitute a predictive gene signature to discriminate resistant patients to NAC before the treatment in breast cancer tumors. Citation Format: Maria Rosario Chica-Parrado, Julio Montes-Torres, Cynthia Robles-Podadera, Martina Alvarez, Jose Jerez, Luis Vicioso, Lidia Pérez-Villa, Begoña Jimenez, Nuria Ribelles, Ana Godoy, Isabel Barragán-Mallofret, Emilio Alba. Gene expression levels of DTX3, CACNA1G, IL11, ETV4 and TSPAN7 selected by LASSO penalty regression could predict pCR after neoadjuvant chemotherapy in breast cancer tumors [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-10-26.

Correlation between Cancer Breast Subtypes and Age at Presentation in Egyptian Patients; Single Institution Experience

Background: Breast cancer is defined according to molecular subtypes. Each molecular subtype defines different disease behavior and requires different treatment. The different molecular subtypes have different risk factors and different distribution across age classes. Aim of the study: To detect the incidence of cancer breast subtypes by age among Egyptian patients treated at the Clinical Oncology Department, Faculty of Medicine, Ain Shams University, in the period between April 2016 and December 2018. Patients and Methods: Inclusion criteria: Cases with proven pathological diagnosis and underwent IHC studies for the molecular subtype while exclusion criteria were: Bilateral cases, cases with unknown molecular subtype or age at presentation, cases with multiple primaries, cases with in situ cancer, male breast cancer cases, and cases diagnosed during pregnancy. Age classes were computed in four groups: from 20 - 35, >35 - 50, >50 - 65 and those older than 65 years of age. Immunohistochemical studies were done; ER, PR and HER2 were recorded for each case, Molecular subtypes were defined as follows: HR+/HER2-, HR+/HER2+, HER2 overexpressed (HER2 positive, HR-) and Triple Negative Breast Cancer; TNBC (HER2 negative, ER negative and PR negative). Results: one thousand and two cases were included in the study. The median age was 51 years and the mean age was 51.64 ± 11.74, with range from 24 to 85 years. The total number of ER positive patients was 706 patients (70.5%), the total number of PR positive patients was 667 (66.6%), and the total number of Her2 positive patients was 286 patients (28.5%). While there were no statistically significant differences in the incidence of ER and PR positivity among all age classes, Her2 over expression decreased with age and the difference was statistically significant (P-value: 0.012). Her2 overexpression subtype incidence decreased by age and it was highest in the younger age group 17.6% compared to 8.2% in the older age group and the difference was statistically significant. Similarly, HR+/HER2- tumors incidence were higher in patients older than 65 (57.4%) and lower in the younger age group (40.5%) (P-value: 0.031). Triple negative tumors incidence ranged from 14.9% for those younger than 35 to 17.2% for those older than 65 years. Conclusion: This study shows that there are significant differences in the age distribution by molecular subtype and the incidence of Her2 overexpression subtype decreases by age. The study also shows that the nature of the breast cancer in the group of Egyptian patients studied is more of the favorable hormonal positive subtype.

Estrogen and progesterone receptor status in meningioma and its correlation with mib-1 labeling index

Introduction: Meningiomas are mostly benign tumour and major prognostic factor for recurrence is mostly dependent on the histopathological category, proliferation indices, grading and estrogen (ER) and progesterone (PR) receptor status. The present study was undertaken to find ER, PR receptor in excised specimen of meningioma and its correlation with Ki67 labelling index. Materials and Methods: 75 cases of meningioma collected over period of 2 years was subjected to Haematoxylin and Eosin staining for routine histopathological investigation and immunohistochemical staining against PR, ER and Ki-67 by means of mouse monoclonal antibodies. Ki-67 labelling index was determined and Histological grade, PR, ER receptor status was evaluated. Results: The Mean Ki-67 LI was significantly higher in PR-negative versus PR-positive meningioma, Grade II versus Grade I and males versus females. Whereas the PR positivity was significantly higher in Grade I versus Grade II and females versus males. A strong converse relationship was established between PR expression and Ki-67 LI. Conclusions: As per the results it has been revealed that immnodetection of ki-67 LI and PR expressions in meningiomas are the important indicators for assessing prognosis and recurrence rate in meningioms. Keywords: Meningiomas, Histopathology, Ki67, Progesterone, Estrogen, Haematoxylin, Eosin

Expression of Estrogen, Progesterone Receptors, and Human Epidermal Growth Factor Receptor 2 in Women With Breast Cancer

Abstract Introduction Globally, breast cancer is a leading cause of female cancer-related mortality and most predominant in the premenopausal stage. Expression of hormone receptors and human epidermal growth factor receptor 2, HER2/neu, appears to be different in the premenopausal group. However, there are limited data on hormone receptor expressions among women in Uganda. Therefore, the objective of this study was to determine the expression of estrogen, progesterone receptors, and human epidermal growth factor receptor 2 in women with breast cancer. Methods This was a retrospective descriptive cross-sectional laboratory-based study conducted in the Department of Pathology, Makerere University. Paraffin-embedded tissue blocks were retrieved from the archive and stained with H&amp;E for histological confirmation and establishment of histological grade and type. Immunohistochemistry staining using a mouse-derived monoclonal antibody for hormonal receptors and HER2/neu expression was also done. Data were analyzed using STATA version 13. Results A total of 103 patients’ tissue blocks were analyzed. The mean ± SD age of the cases was 49 ± 15 years. The majority, 55/103 (53.4%), had intermediate cancer grade and 39/103 (37.9%) had triple-negative breast cancer. The majority, 55/103 (53.4%), were positive for ER hormone expression, 48/103 (46.6%) showed positive PR hormone expression, and only 19/103 (18.5%) were HER2/neu positive. Age of the cases showed statistical significance with hormonal receptor expressions and triple-negative breast cancer (P &lt; .05), with high-grade cancers being more common among premenopausal women. Conclusion The study found that the mean age of breast cancer was 49 years, invasive carcinoma of no special type (NST) was the commonest histological type, and the majority were of intermediate cancer grade. In total, 53.4% of patients were ER positive, 46.6% were PR positive, 18.5% were HER2/neu positive, and 37.9% were triple negative. Age was the only factor significantly associated with hormonal receptors and triple-negative breast cancers.

Male Breast Cancer—an Indian Multicenter Series of 106 Cases

Male breast cancer (MBC) accounts for < 1% of all breast cancers. The available data on male breast cancer is mainly retrospective institution-based studies. Due to the scarcity of the disease, randomized controlled trials have not been feasible. Conducting a multicenter study is the next best option to assess the effectiveness of the treatment which is currently followed as per the guidelines on female breast cancer (FBC). Under the aegis of Delhi Breast Oncology Group (DBOG), data of 106 MBC patients was collected from 11 leading hospitals of Delhi and analyzed from January 2010 to April 2017. The age of the patients ranged from 35 to 82 years with a median of 59 years. The commonest presentation was a lump in the breast (98%). There was a delay in presentation of 1–6 months in the majority (86%) of cases. of the total number of patients, 51% had Stage II, 25% Stage III, 18% Stage I, 4% Stage 0, and 2% Stage IV breast cancer at the time of presentation. Infiltrating ductal carcinoma was the commonest histopathological finding. IHC receptor studies revealed ER positivity in 81% and PR positivity in 76%. HER2 neu positivity was seen in 25% of cases. Modified radical mastectomy was the commonest (92%) surgical procedure. Of the total number of cases, 18% received neoadjuvant chemotherapy, 35% received adjuvant chemotherapy, 32% underwent radiotherapy, and 74% received hormonal therapy. The 5-year cumulative disease-free survival was 60.7%. MBC is rare and unique. There are differences from FBC with respect to time of presentation, aggressiveness, histopathology, IHC markers, and response to treatment with a poorer outcome. Multicentric prospective studies are recommended for future research.

Electric-field tuning of nonvolatile resistance change and magnetic properties of LaMnO3/PMN-PT(0 1 1) heterostructure

The electric-field control of resistance change (ΔR/R) and magnetic properties has been investigated in the LaMnO3(LMO)/0.71Pb(Mg1/3Nb2/3)O3-0.29PbTiO3 (PMN-PT)(0 1 1) heterostructure. When the unipolar electric field (E) increases beyond the coercive field of PMN-PT, the ΔR/R vs E curve transforms from a loop-like behavior to a butterfly-like one. The electric-field-induced non-linear strain effect in the PMN-PT substrate realizes the modulation between low and high resistance states at room temperature. Moreover, different freezing temperatures of the LMO film are observed as the PMN-PT substrate is in the fully negative (Pr-) and partially positive (Pr//) polarization states. The observation of less magnetization for Pr// state than that for Pr- state indicates that the in-plane tensile strain is beneficial to the Jahn-Teller distortion.

Hormone receptor expression of colorectal cancer diagnosed during the peri-partum period.

BackgroundColorectal carcinoma (CRC) during the peri-partum period is challenging to diagnose due to the overlapping symptoms of CRC and pregnancy. This is the first case series to investigate clinicopathologic, hormonal and molecular features of CRC diagnosed during the peri-partum period. We hypothesized that advanced presentations of CRC could possibly be mitigated by pregnancy-related hormonal factors.MethodsWe conducted a retrospective review of five women diagnosed with CRC during the peri-partum period and studied the clinical and molecular features of their cancer.ResultsAll patients presented with stage IV CRC at diagnosis; three had primary tumors in the rectum and two had primary tumors in the sigmoid colon. The liver was the most common metastatic site (three of five women). Immunohistochemistry stains were negative for estrogen receptors alpha (ERα) and beta (ERβ), and one tumor demonstrated low-level positivity for PR (1%). Formalin-fixed and paraffin-embedded (FFPE) biopsies from each case were tested with next-generation sequencing and found that all tumors were mismatch repair (MMR) proficient, and three harbored a KRAS mutation. Germline testing showed no predisposition to CRC; however, several somatic variants of undetermined significance (VUS) were identified.DiscussionCRC in the peri-partum period poses significant risk factors for presentations with advanced disease due to diagnostic challenges. While our study provides no evidence that pathogenesis of CRC during pregnancy is driven by elevated estrogen and/or progesterone levels during pregnancy, additional putative etiologic factors, including placental growth factors, the immunosuppressive state of pregnancy and other physiologic processes during pregnancy, warrant future study.

Role of p53 and Ki-67 in prognostication of carcinoma breast

Role of p53 and Ki-67 in prognostication of carcinoma breast - IJPO- Print ISSN No: - 2394-6784 Online ISSN No:- 2394-6792 Article DOI No:- 10.18231/j.ijpo.2019.051, Indian Journal of Pathology and Oncology-Indian J Pathol Oncol

Analysis of AKR1B10 levels among various groups of breast cancer patients.

e14548 Background: Aldo-keto reductase 1B10 (AKR1B10) is a protein that is primarily expressed in human colon and small intestine, but induced in hepatocellular carcinoma and non-small cell lung cancer. Our recent studies have revealed that AKR1B10 is overexpressed in primary, metastatic, and recurrent cancers of the breast. Methods: We recruited four cohorts of patients: Patients with breast cancer undergoing primary surgery from whom we procured breast cancer and matched normal adjacent tissue to evaluate AKR1B10 expression in primary tumors. The matched serum samples were collected before surgery and at various time points after the surgery (approximately 3 days, 7 days, and 1 month Patients with recurrent or advanced (metastatic) breast cancer. Serum samples were collected and serially monitored for up to 2years before and during metastatic therapy and correlated with RECIST measurements. Patients with locally advanced disease undergoing neoadjuvant chemotherapy. AKR1B10 serum levels were monitored during therapy and correlated with RECIST measurements. Healthy individuals with normal mammograms were recruited and submitted serum samples for AKR1B10 serum measurements. Results: AKR1B10 rapidly cleared the serum of early stage breast cancer patients with an estimated half-life of 24-30 hours. Serum AKR1B10 levels correlated strongly with tissue IHC staining and PR positivity but not with RECIST levels or Oncotype Dx scores. Neoadjuvant chemotherapy did not affect serum AKR1B10 levels. Individuals with normal mammograms displayed substantially lower levels of AKR1B10 than breast cancer patients. Patients with DCIS also displayed elevated serum AKR1B10 levels. Conclusions: AKR10 may serve as tumor marker to independently identify high risk patients whose tumors have intermediated risk Oncotype Dx scores and may also identify early breast cancers in patients with equivocal breast biopsies.

Clinical behavior of recurrent hormone receptor-positive breast cancer by adjuvant endocrine therapy: A Breast International Group (BIG) 1-98 sub-analyses.

538 Background: Endocrine therapy resistance is a major cause of distant recurrence (DR) in HR+ breast cancer. Currently, no data exists evaluating differences in clinical behavior after DR between patients (pts) treated in the adjuvant setting with different endocrine therapy regimens. The aim of this study was to analyze post-DR survival of pts treated on BIG 1-98. Methods: BIG 1-98 compared 5 years of adjuvant treatment between 4 arms: tamoxifen (T), letrozole (L), T followed by L (TL) and L followed by T (LT). After 8.1 years median follow-up (follow-up through 2010), 911 (T n = 302, L n = 285, TL n = 170, LT n = 154) of 8010 pts had DR as site of first recurrence. Univariate and multivariable Cox analyses were performed to determine features associated with post-DR survival. With 661 total observed deaths, statistical power was 0.8 to detect a hazard ratio (HaR) &gt; 1.24 at the 2-sided 0.05 level of significance. Results: Median follow up time after DR was 59 months (IQR: 29-88). Among all pts with DR, 38.1% were ≥ 65 years at study enrollment, 61.9% had tumor size &gt; 2 cm, 69.7% were node positive. Neo/adjuvant chemotherapy was administered to 35.6% of pts. There was no difference in post-DR survival by treatment arm (median survival: T 20.8, L 17.9, TL 17.3, LT 20.8 months; p = 0.21). In multivariable analysis, older pts (HaR 1.36; p = 0.0002), tumors &gt; 2cm (HaR 1.2; p = 0.04), ≥ 4 positive nodes (HaR 1.32; p = 0.05) and PR- tumors (HaR 1.28; p = 0.001) had significantly worse post-DR survival. Endocrine treatment arm, type of surgery, radiotherapy and neo/adjuvant chemotherapy were not associated with post-DR survival in the multivariate model. Conclusions: Treatment with adjuvant T, L or their sequence were not associated with differences in survival after DR. We observed significant differences in survival by primary tumor size, nodal and PR status, which suggest that traditional high-risk features remain prognostic in the metastatic setting. Clinical trial information: NCT00004205.

SUN-352 Estrogen, Progesterone, and Androgen Receptor Expressions Predict the Prognosis for Adrenocortical Carcinoma

Aim: Adrenocortical carcinoma (ACC) is a rare but mortal endocrine malignancy. While expression of sex steroid receptors is well-known to be associated with tumor prognosis and treatment response in a number of hormone sensitive cancers, sex steroid receptor expression in ACC is not revealed in this context. The aim of this study is to assess prognostic implications of sex steroid receptor expression in ACCs. Method: Paraffin-embedded blocks of 16 ACC cases (8 F, 8 M, mean age 47.9±13.9) and 22 benign adrenocortical adenoma (ACA) cases (14 F, 8 M, mean age 50.0±11.4) who were undergone surgery in our center between 1998-2017 were examined in this case-control study. Estrogen (ER, Leica), androgen (AR, CellMarque) and progesterone receptor (PR, Leica) expressions in both tumor and peritumoral adrenal tissue were semi-quantitatively scored by immunohistochemistry (IHC), by an endocrine pathology specialist. The relationship between the histopathological prognostic indicators, the clinical course of patients and intra-tumor and peritumoral sex steroid receptor expression status were examined. Results: ER and AR expressions of ACCs were significantly higher, while all ACAs were ER and AR negative (ER 25% vs 0%, p=0.014; AR 31% vs 0%, p=0.005). PR expression was similar between groups; although, higher rate of PR expression was observed in ACAs (75% vs 86%, p=0.38). While peri-tumoral adrenal tissue of ACC cases did not express none of the three sex steroid receptors, IHC staining of peripheral adrenal tissue of ACAs revealed positivity for ER, AR and PR (p values <0.005). ACC cases which were negative for ER, PR and/or AR had larger tumor size (r=-0.6, p=0.015). Tumor stage was more advanced in AR negative ACCs (r=-0.6, p=0.021). Progression free survival was shorter in ACC cases which were positive for PR (15 vs 57.5 months, p=0.07); while it was longer in cases peritumoral adrenal tissue was positive for either of three sex steroid receptors (r=0.81, p=0.008). Conclusions: For the first time in this study, expression of sex steroid receptors has been shown to be related with ACC prognosis and clinical/histopathological behaviour.

Metastatic breast cancer to colon: An unusual site of metastasis with a review of literature

Gastrointestinal (GI) metastasis is very rare in patients with breast cancer (BC). This study reports a case with colon carcinoma metastasis originated from breast cancer in Western Iran. A 37-yearold female was diagnosed with infiltrating ductal carcinoma. Immunohistochemistry (IHC) results showed positive estrogen receptor, progesterone receptor, HER2 scored 2 out of 3, Ki-67 in 30% of tumor cells and P53. The patient was re-admitted two times with urinary and GI symptoms, positive tumor markers and thick colon wall. Samples from the colon were collected to test for metastasis. The pathologist reported metastatic breast ductal carcinoma spread to the colon. The IHC showed CK7, CK20, GCDFP15, ER and PR positivity. In conclusion, this IHC panel can be considered as the differential and diagnostic markers for malignant GI lesion originated from breast cancer.&#x0D;

Breast cancer: correlation of receptor status with clinical presentation, stage of disease, histopathological grade and short term outcome

Background: Breast cancer is the commonest female cancer representing a quarter of all cancers worldwide. An important development in breast cancer management was the realization of role of hormone receptors in disease. Thus, the present study was carried out to evaluate the receptor status and its correlation with clinical presentation, stage, grade and short term outcome.Methods: All female patients with lump in breast confirmed as breast cancer were included and their receptor status was evaluated using immunohistochemistry.Results: A total of 147 patients with a mean age of 50.16±12.08 years were enrolled. Almost half of the patients (48.3%) of the patients were found to have locally advanced breast cancer. Of the 147 patients, 91.49% tumours were either Nottingham grade 2 or 3. Triple negative breast cancer (TNBC) was the commonest subtype seen in 43.54% patients. On correlating the results with receptor status, it was found that TNBC patients were younger than HER2neu positive and ER PR positive patients. Also, TNBC patients had a longer duration of lump and the lump was of larger size at presentation. On correlating receptor status with tumour biology it was seen that more than half (54.69%) of the patients who were triple negative had a grade 3 tumour and poorer disease free survival and overall survival.Conclusions: In conclusion it is seen that TNBC forms a majority of the cases in the central Indian population with more aggressive presentations and outcomes. Absence of any targeted therapies against them leads to a worse DFS and overall survival.

Abstract P1-09-10: Molecular and genetic characterisation of contralateral breast cancers in Northern Ireland: Opportunities for personalised surgery

Abstract Contralateral breast cancer (CBC) incidence is reported as 0.4-0.7% per year, equating to an approximate 10-15% 20 year risk after primary cancer diagnosis. Young age at primary diagnosis and a strong family history are consistently cited as significant risk factors for CBC development. Requests for contralateral prophylactic mastectomy (CPM) are rising, despite a lack of evidence that CPM significantly improves breast cancer specific survival. Therefore, a method to stratify CBC prognosis and risk at an individual level is required to allow us to personalise surgical decision-making for individual patients. This study aims to: 1. Explore prognostic factors following CBC diagnosis; 2. Investigate metastatic CBC prevalence by determining clonal relationships between primary and CBC tumours; 3. Assess the rate of germline predisposition gene mutations in a large cohort of Northern Irish CBC cases. A cohort of 403 CBC patients and 1:1 matched unilateral breast cancer controls (matched for age, year of diagnosis, nodal positivity and tumour morphology) were identified from the Northern Ireland Cancer Registry. Archival primary, CBC and normal lymph node tissue from these CBC patients were obtained for somatic and germline sequencing of a custom 94-gene panel, comprising genes most commonly mutated in breast cancer and all known predisposition genes. CBC patients had a significantly increased risk of breast cancer specific mortality when compared with 1:1 matched unilateral breast cancer controls (HR 6.45, CI 4.27-9.77). Within the CBC cohort, a shorter time interval between primary and CBC diagnosis is associated with increased breast cancer mortality, whereby women with &amp;lt;5 years between diagnoses have the poorest survival (p=0.001). In terms of receptor status, the PR status of ER positive primary and CBC tumours differed significantly (p&amp;lt;0.001). 89.1% of ER positive primary tumours were PR positive, whilst PR positivity was only 54.4% in ER positive CBCs. Indeed, 36.6% of patients with an ER+/PR+ primary BC developed an ER+/PR- CBC, after exposure to anti-oestrogen therapy. Targeted next generation sequencing of 42 cases to date has provided evidence of shared somatic mutations suggestive of metastatic clonality between primary and CBC in four cases (9.5%). Germline pathogenic predisposition gene mutations were identified in five (11.9%) patients and a further ten (23.8%) patients were noted to have germline predisposition variants of unknown significance. Breast cancer specific mortality risk was significantly higher in CBC patients compared with matched unilateral cancer controls, in excess of what would be expected from two primary cancer events. This finding suggests that there are as yet unquantified factors contributing to this excess hazard. Poorer outcome with shorter inter-tumour diagnostic intervals, in addition to evidence of primary-CBC clonality in some cases, suggests that metastatic CBC may play a role in excess risk. Additionally, the significant reduction in PR positivity of ER positive CBC tumours after ER+/PR+ primary tumours, could suggest that acquired hormonal resistance following primary anti-oestrogen therapy exposure may contribute to this additional mortality hazard. Citation Format: McIlmunn CG, Bannon FJ, Fitzpatrick D, Ervine A, Boyd C, Cameron I, Harita T, James J, Gonzalez de Castro D, Savage KI, McIntosh SA. Molecular and genetic characterisation of contralateral breast cancers in Northern Ireland: Opportunities for personalised surgery [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 P1-09-10.

Abstract OT1-13-01: MammaPrint, BluePrint, and full-genome data linked with clinical data to evaluate new gene expression profiles (FLEX)

Abstract BACKGROUND: Genomic signatures are revolutionizing the definition, identification, and treatment of breast cancer subtypes. The ability of genomic signatures to enable fine grained stratification of breast cancers to the granular disease level is still generally untested because of the difficulties in aggregating large clinical data sets. In order to stratify breast cancers into actionable subtypes both the full genome data and clinical data must be collected for patients at scale. DESIGN &amp; METHODS: FLEX is designed as a novel, large-scale, population based, prospective registry. All patients with stage I-III breast cancer who receive MammaPrint (MP) or BluePrint (BP) testing on a primary breast tumor are eligible. FLEX utilizes an adaptive design which enables additional study arms at low incremental effort and cost by allowing targeted substudies to be added. Patients who are enrolled in the initial study will also be eligible for inclusion in any additional study arm where they meet all criteria. Additional study arms and substudies may be investigator-initiated. SPECIFIC AIMS: Primary: Create a big-data registry of full genome expression data and clinical data to investigate new gene associations with prognostic and/or predictive value. Secondary: Generate hypotheses for targeted subset analyses and trials based on full genome data. To date the following substudies have been proposed: DR. JENNIFER A. CROZIER, BAPTIST MD ANDERSON CANCER CENTER (1) MP and BP in male breast cancer TYPE: SUBSTUDY; NO ADDITIONAL CONSENT (ICF) REQUIRED. ARMS: ALL (2) MP BP evaluation in breast cancer patients ≥70. TYPE: SUBSTUDY; NO ADDITIONAL ICF REQUIRED. ARMS: ALL (3) FG evaluation in ILC. TYPE: SUBSTUDY; NO ADDITIONAL ICF REQUIRED. ARMS: ALL (4,5) MP BP relation to PR positivity, Ki67. TYPE: SUBSTUDY; NO ADDITIONAL ICF REQUIRED. ARMS: ALL (6) MP BP in metaplastic breast cancer. TYPE: SUBSTUDY; NO ADDITIONAL ICF REQUIRED. ARMS: ALL DR. ADAM M. BRUFSKY, UNIVERSITY OF PITTSBURGH MEDICAL CENTER MAGEE WOMENS HOSPITAL (1) Response to standard chemotherapy regimens in clinically ER+/PR+/HER2+ (triple positive) patients according to BP molecular subtypes. (2) Expression signatures by response to bisphosphonates in ER+ patients receiving adjuvant therapy, or for osteoporosis after primary treatment. (3) Gene expression in breast cancer patients with obesity. TYPE: SUBSTUDY; DUAL ICF UTILIZED. ARMS: NEOADJUVANT AND ADJUVANT DR. IAN GRADY, NORTH VALLEY BREAST CLINIC Impact of genomic risk classification on travel time to receive breast cancer care. TYPE: SUBSTUDY; NO ADDITIONAL ICF REQUIRED. ARMS: ALL DR. THOMAS LOMIS, VALLEY BREAST CARE Complementary data collection for patients participating in the ODM-201 trial. FLEX provides gene expression for exploratory and signature discovery. TYPE: COMPLEMENTARY; DUAL ICF UTILIZED. ARM: NEOADJUVANT DR. PAT WHITWORTH, NASHVILLE BREAST CENTER Genomic reclassification of large tumors eligible to receive NCT therapy. TYPE: SUBSTUDY; NO ADDITIONAL ICF REQUIRED. ARM: NEOADJUVANT ELIGIBILITY, ACCRUAL FLEX will enroll a minimum of 10000 patients aged ≥18 with stage I-III breast cancer who sign ICF. Enrollment began April 2017 and 623 patients have been enrolled as of June 2018. Citation Format: Brufsky AM, Crozier JA, Grady I, Lomis T, Whitworth P, Rehmus E, Srkalovic G, Lee L, Blumencranz P, Baron P, Mavromatis B, Untch S, Blumencranz L, Yoder EB, Audeh W, FLEX Investigators Group. MammaPrint, BluePrint, and full-genome data linked with clinical data to evaluate new gene expression profiles (FLEX) [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 OT1-13-01.

Bcl-2 expression and prognostic significance in feline invasive mammary carcinomas: a retrospective observational study

BackgroundCats spontaneously develop invasive mammary carcinomas with high clinical aggressiveness, and are considered relevant animal models for human breast cancer. Bcl-2 is an anti-apoptotic pro-survival protein, whose expression is associated with a favorable outcome in human breast cancer. The aim of our study was to determine the frequency of Bcl-2 expression in feline invasive mammary carcinomas (FMCs), its relationship with other clinicopathologic variables, and its prognostic value. This retrospective study included 180 FMCs, diagnosed in female cats treated by surgery only, with a 2-year follow-up post-mastectomy. Bcl-2, ER, PR, Ki-67, HER2, and CK5/6 expression were determined by automated immunohistochemistry. A receiver-operating-characteristic curve was used to set the threshold for Bcl-2 positivity.ResultsThe cohort comprises 32% (57/180) luminal FMCs defined by ER and/or PR positivity, and 68% (123/180) triple-negative FMCs (negative for ER, PR, and HER2). Bcl-2 expression was considered as positive when at least 65% of tumor cells were immunohistochemically stained. Thirty-one out of 180 FMCs (17%) were Bcl-2-positive. There was no significant association between Bcl-2 expression, and the tumor size, nodal stage, histological grade, or ER, PR, Ki-67, HER2, and CK5/6 expression. By multivariate survival analysis (Cox proportional-hazards regression), Bcl-2 positivity in FMCs was associated with longer disease-free interval (p = 0.005, HR = 0.38), overall survival (p = 0.028, HR = 0.61), and cancer-specific survival (p = 0.019, HR = 0.54) independently of other powerful prognostic factors such as pathologic tumor size, pathologic nodal stage, and distant metastasis. The positive prognostic value of Bcl-2 was confirmed in both luminal FMCs, of which 9/57 (16%) were Bcl-2-positive, and in basal-like triple-negative (ER–, PR–, HER2–, CK5/6+) FMCs, of which 14/76 (18%) were Bcl-2-positive.ConclusionsCompared to human breast cancer, Bcl-2 positivity in feline invasive mammary carcinomas is also associated with better outcome, but is less common, and not associated with ER, PR, and HER2 expression. Cats with spontaneous Bcl-2-positive FMCs could be useful in preclinical trials evaluating anti-Bcl-2 strategies for chemoresistant luminal or triple-negative breast cancers.