bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II trial of single-agent ganetespib (STA-9090), a heat shock protein 90 (Hsp90) inhibitor in heavily pretreated patients with metastatic castration-resistant prostate cancer (mCRPC) post docetaxel-based chemotherapy: Results of a Prostate Cancer Clinical Trials Consortium (PCCTC) study.
Authors: Heath Elisabeth I. , Stein Mark N. , Vaishampayan Ulka N. , Antonarakis Emmanuel S. , Liu Glenn , Sheng Shijie , Farrow Katherine , Smith Daryn W. , Heilbrun Lance K. 
Published: March 2020

5085 Background: Hsp90 is a molecular chaperone required for the proper folding and activation of numerous client proteins and is critical to cell survival and proliferation. Ganetespib (G), a synthetic small molecule that binds to the ATP pocket in the N-terminus of Hsp90 causes the degradation of cellular proteins and ultimately death of cancer cells dependent on these proteins. G displays potent anticancer activity in prostate cancer cells. Methods: Eligible patients were ≥ 18 yrs old with ECOG performance status ≤ 2. Adequate hepatic, renal, and bone marrow function was required. Patients were treated with G 200 mg/m2 intravenously once weekly for 3 consecutive weeks followed by 1 off-week. The primary objective was to evaluate the 6-month progression-free survival (PFS). Secondary endpoints included overall safety and tolerability of G and overall survival. Exploratory markers including maspin, cytokeratins 8 and 18, and HDAC1 were obtained pre, during, and post G treatment. We sought ≥ 4 patients with ≥ 6 months PFS (a success) in Stage 1 of a 2-stage near-optimal Simon design. Results: 18 patients were enrolled at 4 institutions. The patients’ median age was 68 (range 51-82), 13 were Caucasian, 4 were African American, and 1 was Asian. Median PSA was 210.7 ng/mL (range 25.9 – 3,489 ng/mL). One patient never started therapy. Among the 17 treated patients, the median number of cycles was 2 (range 1-5). The most frequent Grade 3 toxicities were diarrhea (3 patients), fatigue (3), and dehydration (3). Prior therapy included abiraterone (8), sipuleucel-T (4), and other targeted therapy (4). With < 4 successes in Stage 1, the trial was terminated early. Median PFS was 1.9 months (90% CI: 1.7 – 2.7 months); median OS was 10.2 months (90% CI: 2.3 – 18.3 months). Exploratory markers have been evaluated and will be presented. Conclusions: Our study represents the first clinical trial of G in treating mCRPC patients. As a single agent therapy, G did not prolong PFS. Combination therapy is a consideration to improve therapeutic efficacy. Clinical trial information: NCT01270880.
Phase II randomized study of the EGFR, HER2, HER3 signaling inhibitor AZD8931 in combination with anastrozole (A) in women with endocrine therapy (ET) naive advanced breast cancer (MINT).
Authors: Johnston Stephen R. D. , Basik Mark , Hegg Roberto , Lausoontornsiri Wirote , Grzeda Lukasz , Clemons Mark , Dreosti Lydia Mary , Ghiorghiu Serban , Mann Helen , Landers Donal , Stuart Mary , Cristofanilli Massimo 
Published: March 2020

531 Background: Preclinical data suggest a key role for EGFR inhibition in delaying acquired resistance to ET in ER+ breast cancer (BC). Retrospective analyses of 2 Phase II studies suggested adding gefitinib to ET delayed PFS in ET naive (ETN) BC. This randomized, double-blind, placebo-controlled multi-center study (NCT01151215) was conducted to prospectively test the hypothesis that adding AZD8931, an inhibitor of EGFR, HER2 and HER3 signaling, to A would be beneficial in delaying endocrine resistance in an advanced ETN BC population. Methods: Post-menopausal women with ER+ and/or PR+, ETN, HER2-negative, advanced BC were randomized (1:1:1) to receive A (1 mg od) plus AZD8931 20 or 40 mg bd or placebo (P). The primary endpoint was PFS (ITT population). Data presented are from an interim analysis (data cutoff 31 Aug 2012; 39% pts had a progression event). Results: Between Jun 2010 and Jun 2012, 359 pts (median age 61 years) were randomized to A combined with AZD8931 20 mg (n=118), 40 mg (n=120) or P (n=121). At the interim analysis, median PFS in the AZD8931 20 mg, 40 mg and P arms was 10.9, 13.8 and 14.0 months, respectively; PFS HR (95% CI) for AZD8931 20 mg:P was 1.37 (0.91–2.06, P=0.135) and for AZD8931 40 mg:P was 1.16 (0.77–1.75, P=0.485). Deaths were reported for 20 (17%), 16 (13%) and 12 pts (10%) in the AZD8931 20 mg, 40 mg and P arms, respectively. Grade ≥3 AEs were reported for 22 (19%), 44 (37%) and 18 (15%) pts in the AZD8931 20 mg, 40 mg, and P arms, respectively, the most frequent being rash (0% vs 8% vs 2%), acneiform dermatitis (0% vs 7% vs 0%) and hypertension (3% vs 3% vs 2%). Serious AEs were reported for 12%, 14% and 9% pts in the AZD8931 20 mg, 40 mg and P arms, respectively, and discontinuation (of AZD8931 or P) due to an AE in 5%, 8% and 2% pts, respectively. Conclusions: Co-blockade of EGFR, HER2, HER3 in combination with aromatase inhibition does not appear to delay endocrine resistance to ETN BC. Based on the low probability of demonstrating superior efficacy with addition of AZD8931 to A and the overall risk/benefit, the study was closed at the recommendation of the IDMC and pts discontinued AZD8931. Clinical trial information: NCT01151215.
Single nucleotide polymorphisms to predict for neoadjuvant chemotherapy in breast cancer according to estrogen receptor (ER) status.
Authors: Pannier Diane , Dumont Aurelie , Tresch Emmanuelle , Chen Jinying , Ducoulombier Agnes , Revillion Francoise , Bonneterre Jacques , Peyrat Jean-Philippe 
Published: March 2020

544 Background: Neoadjuvant chemotherapy (NCT) using anthracyclines and taxanes is a standard treatment for locally advanced breast cancer and pathologic complete response (pCR) is a major prognostic factor for survival. Gene polymorphisms have been identified as modulators of chemotherapy response. Our study investigated constitutional variants of genes associated with a change in the response to neoadjuvant chemotherapy using taxanes and/or anthracyclines in patients with breast adenocarcinoma. Methods: From November 2007 to January 2012, 118 women with breast adenocarcinoma histologically proven, with no Her2 surexpression, receiving or having received a neoadjuvant chemotherapy with taxanes and/or anthracyclines were included in the study. NCT associated 3 FEC100 then 3 Docetaxel every 21 days. Genotyping of 46 SNPs was performed on germline DNA using real time PCR. pCR was correlated to clinical characteristics and genotypes using univariate logistic regression. Results: 21.2% had a pCR according to Sataloff classification. pCR is increased in SBRIII (p=0.009), estrogen receptor negative (p=0.005) and triple negative (p=0.006) tumors. 7 SNP are significantly associated with pCR in ER+ breast tumors (pCR=13.5%). Among these SNP, pCR is increased for patients carrying almost one G allele for SLCO1B3-rs11045585 (pCR=28.6%; p=0.032), for homozygotes GG for SHTM1-rs1979277 (pCR=24.3%, p=0.006) and for homozygotes CC for CYP1B1-rs1056836 (pCR=25.7%; p=0.003). Moreover, 4 SNPs are significantly associated with pCR in ER- breast tumors: ERCC1-rs11615 (carriers of almost one C allele: pCR=50%; p=0.030), CD24-rs52812045 (Homozygotes CC pCR=56.3%, p=0.033), CYP2B6-rs2279343(carriers of one or two G allele: pCR=52.6%; p=0.046) and GSTP1-rs1695 (carriers of one or two G allele: pCR=48%; p=0.050). Conclusions: Besides ER status, polymorphisms could be useful markers to predict response to anthracyclines/taxanes NCT in breast cancer. Furthermore, this work is the first describing ERCC1-rs11615, SLCO1B3-rs11045585 and SHTM1-rs1979277 as new potential genetic markers for NCT in breast cancer. (The first 3 authors contributed equally to this work.)
Clinical significance of ERβ mRNA expression in ERα-negative and triple-negative breast cancers.
Authors: Kim Young Choi , Kim Hadong , Kim Tae-Hoon 
Published: March 2020

545 Background: Previously at the 2012 ASCO meeting, we reported significant ERβ mRNA expression in ERα-negative (ERα-) and triple negative breast cancers (TNBC). In this study, we analyzed its clinical outcome and correlation with other clinical parameters. Methods: A total of 141 cases consisted of 69 ERα- BC including 41 TNBC and 72 ERα+ BC were obtained from patients aged 29 to 97 years old between 2003 and 2010. Treatments included surgery, hormone, chemo- or radiotherapy, or any combinations. The follow-up period ranged from 1 to 132 months. ERβ mRNA was analyzed from formalin-fixed tumor tissues by RT-PCR. ERα, PR, Her-2, Ki-67, AIB-1, NFk/p65, p-c-jun, Ki-67, TIF-2, SRC-1, CK5/6 and p53 were tested by immunohistochemistry. The correlation was deemed significant if p value less than 0.05 from Chi-square. Overall survival (SVR) was defined from the date of diagnosis to last follow-up or death attributed to BC and was analyzed by the Kaplan-Meier curves and Wilcoxon rank sum. Results: Single or combination of ERβ isoform(s) was highly expressed in both ERα- and TNBC and ERβ2 was the most frequent (48.8%) and ERβ5, the least (30.2%). In contrast, ERβ5 was the most frequent in ERα+BC. Presence of all or any ERβ isoform was associated with significantly higher SVR in all cases, and in TNBC (ERβ total, Wilcoxon p = 0.0177, ERβ2, p= 0.0329), and also with negative LN (p< 0.0001). ERβ2 and ERβ5 were expressed in 63.2% and 30 %, respectively, in 20 patients died in 1 to 60 months. Over expression of AIB-1, NF-kB/p65 and TIF-2 was associated with ERβ1 and ERβ2 (p<0.05). Ki-67 + cells were mostly ERβ + BC than ERα+. ERα mRNA expression was up-regulated, and ERβ,down- regulated, with the ERα: ERβ+ ratio of 3-1000:1. There was no association between ERβ expression and the stage, age, tumor size, and postmenopausal status. Conclusions: Specific ERβ isoform appears to be a significant discriminating factor for SVR and negative node. ERβ2 is the predominant isoform in ERα- but ERβ5 in ERα+BC, suggesting a distinct role of ERβ isoform in ERα- and ERα+BC. ERβ isoform may be a selective therapeutic target in this cohort. ERβ+/ Ki-67+cells appear to be a sub-population of BC arising from basal-myoepithelial cells in this cohort.
Post-surgical highly sensitive C-reactive protein (hsCRP) and prognosis in early stage in breast cancer (BC).
Authors: Tibau Martorell Ariadna , Goodwin Pamela Jean , Ennis Marguerite 
Published: March 2020

550 Background: Obesity, commonly associated with inflammation, is associated with poor prognosis in BC. Previous research suggests CRP, an obesity-associated marker of systemic inflammation, may mediate the adverse prognostic effects of obesity and be associated with fatigue. We examined the association of hsCRP with obesity-related factors, fatigue and distant disease-free and overall survival (DDFS, OS) in an early BC cohort. Methods: 501 non-diabetic women with T1-3, N0-1, M0 BC diagnosed 1989-96 provided fasting blood (mean 7.7 ± 4.3 weeks after surgery, prior to systemic therapy, stored at -80°C) which was analyzed for hsCRP (Roche Elecsys immunochemistry). 359 women also completed the EORTC QLQ-C30 (mean 8 ± 3.9 weeks post-surgery). Women were followed prospectively to 2007. Data were analyzed using Spearman's rank correlation coefficients (r) and Cox models. Results: Mean age was 50.5 ± 9.7 years; 282/159/24/36 subjects had T1/T2/T3/TX cancers; 350 were N0; 306 had ER+ and 278 PgR+ cancers (HER2 was not performed); 76/208/142 cancers were grade 1/2/3; adjuvant treatment involved radiation (369 subjects), chemotherapy (196), tamoxifen (107). Median hsCRP was 0.9 mg/L (25th/75th percentiles: 0.4/2.4 mg/L). hsCRP was correlated (all p < 0.0001) with age (r = 0.25), Body Mass Index (BMI, r = 0.6), insulin (r = 0.44), Homeostasis Model Assessment (r = 0.45) and leptin (r = 0.54), but not with EORTC fatigue (r = 0.02), T or N stage, grade or ER/PgR status (any + vs. both -). Median follow-up was 12 years. hsCRP was not associated with DDFS or OS in univariate analyses (Q4 vs. Q1 HR 1.03, 95% CI 0.69-1.52, p = 0.9 and HR 1.27, 95% CI 0.86-1.86, p = 0.24 respectively) or multivariate analyses adjusting for age, T, N, grade, ER/PgR status, treatment (HR 1.02, 95% CI 0.66-1.59, p = 0.93 and HR 1.17, 95% CI 0.76-1.81, p = 0.48 respectively). Conclusions: hsCRP (measured post-op, prior to systemic therapy) was associated with age, BMI and obesity associated physiologic factors; it was not associated with fatigue, DDFS or OS. Funded by The Breast Cancer Research Foundation (New York), The Canadian Cancer Society Research Institute (formerly The Canadian Breast Cancer Research Initiative).
Phase II trial of volasertib (BI 6727) versus chemotherapy (CT) in platinum-resistant/refractory ovarian cancer (OC).
Authors: Pujade-Lauraine Eric , Weber Beatrice E. , Ray-Coquard Isabelle , Vergote Ignace , Selle Frédéric , Del Campo Jose Maria , Sufliarsky Jozef , Tschöpe Inga , Garin Chesa Pilar , Nazabadioko Serge , Pilz Korinna , Joly Florence 
Published: March 2020

5504 Background: Volasertib (V) is a potent and selective cell cycle kinase inhibitor that induces mitotic arrest and apoptosis by targeting Polo-like kinases. This study investigated V vs CT as 3rd- or 4th-line therapy in patients (pts) with platinum-refractory or resistant OC. Methods: Pts were randomized to V 300 mg IV Q3W or investigator’s choice single-agent CT (pegylated liposomal doxorubicin, topotecan, paclitaxel, gemcitabine) until progression or intolerance. Primary endpoint was 24-wk disease control rate (DCR; % of pts with complete/partial response [PR] or stable disease [SD]). Secondary endpoints included safety, progression-free survival (PFS), best overall response (RECIST 1.1) and explorative biomarkers. Results: 109 pts received V (n=54) or CT (n = 55) for a median (range) of 95 (22–716) and 114 (7–351) days, respectively. Demographic data were balanced between the treatment arms. Overall, median age was 62.0 yr; ECOG PS 0–1: 103 pts; 2 prior CTs: 51 pts; ≥3 prior CTs: 57 pts; platinum-resistant: 78 pts; platinum-refractory: 31 pts; measurable disease: 89 pts. 24-wk DCR (95% CI) for V vs CT was 31% (18–43) vs 43% (30–57), and median PFS was 13.1 vs 20.6 wks (HR = 1.01; 95% CI: 0.66–1.53). Six V pts vs 0 CT pts are ongoing for PFS 1 yr after randomization. Best overall response in pts with measurable disease (V/CT) was: PR, 7/8 pts; SD, 24/24 pts. Adverse events (AEs) led to discontinuation in 20 pts (V, n = 5; CT, n = 15); no V pts and 8 CT pts discontinued due to treatment-related AEs (including neuropathy in 3 CT pts). Most frequent all grade AEs (% of pts) regardless of relatedness were neutropenia (61%), anemia (54%), thrombocytopenia (46%), nausea (37%) and asthenia (33%) with V, and asthenia/nausea (47% each), abdominal pain (38%), anemia (36%) and neutropenia/vomiting (31% each) with CT. There were 3 fatal AEs per arm. Conclusions: Single-agent V showed antitumor activity in OC in a range similar to CT. AEs with V were mainly hematologic and manageable, with fewer non-hematologic AEs than CT. Exploration of potential predictive biomarkers for V activity is ongoing. Clinical trial information: NCT01121406.
Final results of 4-monthly screening in the UK Familial Ovarian Cancer Screening Study (UKFOCSS Phase 2).
Authors: Rosenthal Adam N , Fraser Lindsay , Philpott Susan , Manchanda Ranjit , Badman Philip , Hadwin Richard , Evans D. Gareth , Eccles Diana , Skates Steven James , Mackay James , Menon Usha , Jacobs Ian 
Published: March 2020

5507^ Background: Annual transvaginal ultrasound (TVS) and serum CA125 screening for women at high-risk of Ovarian/Fallopian tube cancer (OC/FTC) in Phase 1 of UKFOCSS lacked sensitivity for early stage disease but downstaged disease volume and may have improved optimal debulking rates. More frequent screening might provide greater benefits. Here we report the final results of 4-monthly screening in one of the largest such trials worldwide. Methods: Between 14/06/2007 and 29/03/2012, 4,531 women at an estimated ≥10% lifetime risk of OC/FTC were recruited and screened by 42 UK centres for 14,263 women screen years. Screening comprised 4-monthly CA125 tests analysed by a risk of ovarian cancer algorithm, adjusted for menopausal status. TVS was annual in those with normal algorithm results, but was triggered sooner if results were non-normal. Women with suspicious scan and/or algorithm results were referred for consideration of surgical intervention. Participants were followed prospectively by centres, questionnaire and national cancer registries. Data was censored 365 days after final screen, withdrawal or death. Clinical trial information: 32794457.
Impact of body mass index (BMI) on the prognosis of women with high-risk early breast cancer (BC) receiving adjuvant chemotherapy (CT).
Authors: Gennari Alessandra , Nanni Oriana , Scarpi Emanuela , Cecconetto Lorenzo , Sarti Samanta , Amadori Dino 
Published: March 2020

552 Background: Obesity has been shown to impact the prognosis of early BC; this effect was not consistently observed across the different biological subtypes, and is less clear when aggressive tumor phenotypes are considered. The aim of this study was to evaluate the influence of BMI (kg/m2) on the prognosis of women with high risk early BC enrolled into a phase III clinical trial of adjuvant CT. Methods: The relationship between BMI and Disease Free (DFS) or Overall Survival (OS) was assessed in 1066 early BC patients with rapidly proliferating tumors (Thymidine Labeling Index > 3% or G3 or Ki67 > 20%), randomized to receive adjuvant CT with or without anthracyclines (Epirubicin → CMF vs CMF → Epirubicin vs CMF). BMI was defined as follows: normal < 25 kg/m2, overweight 25-30 kg/m2, obese >30 kg/m2. DFS and OS were calculated by Kaplan-Meier estimation; multivariate Cox analysis was performed according to menopausal status, type of CT, hormonal, HER-2 and nodal status. Results: Information on BMI at baseline, was available on 959 women. Of these, 430/959 (44.8%) were normal, 331 (34.5%) were overweight and 198 (20.7%) were obese. Median age was 52 years (range 26 to 70); 48% was node positive, 62% was ER positive and 33% was HER-2 positive. At a median follow-up of 69 mos (range 1-119), 5-year DFS was 80% (95% CI 78-83) and 5-year OS was 94% (95% CI 90–94). 5-year DFS was 81% (95% CI 77-85), 82% (95% CI 77-86) and 76% (95% CI 70-83), in normal, overweight and obese women, respectively (p 0.6). 5-year OS was 92% (95% CI 89-95), 94% (95% CI 91-96) and 89% (95% CI 84-93), respectively (p 0.4). By multivariate analysis only ER, HER-2 and nodal status were significantly associated with differences in DFS and/or OS. Conclusions: BMI at baseline was not associated with the prognosis of early BC patients with rapidly proliferating tumors, receiving adjuvant CT. These results confirm those achieved in triple negative BC and suggest that neither dietary restriction or medical interventions aimed at reducing BMI and/or underlying insulin resistance nor specific anticancer strategies seem to be appropriate in this subgroup.
A phase II trial of lenvatinib in patients with advanced or recurrent endometrial cancer: Angiopoietin-2 as a predictive marker for clinical outcomes.
Authors: Vergote Ignace , Teneriello Michael , Powell Matthew A. , Miller David S. , Garcia Agustin A. , Mikheeva Olga N. , Pinter Tamas , Bidzinski Mariusz , Cebotaru Cristina Ligia , Fan Jean , Ren Min , Meneses Nicole , Funahashi Yasuhiro , Kadowaki Tadashi , O'Brien James P. , Penson Richard T. 
Published: March 2020

5520 Background: Lenvatinib is an oral receptor tyrosine kinase inhibitor targeting VEGFR1-3, FGFR1-4, RET, KIT, and PDGFRβ. The importance of angiogenesis in endometrial cancer (EC) highlights the need to understand clinical mechanisms of escape (eg, angiopoietin-2 [Ang-2]) from antiangiogenic therapy. Methods: Patients (pts) had metastatic/unresectable EC after 1 or 2 prior platinum-based treatments (Tx), ≤2 prior chemotherapies, and ECOG PS ≤2. Pts received lenvatinib 24 mg once daily until disease progression or development of unmanageable toxicities. Primary endpoint was objective response rate (ORR: complete + partial response [CR+PR]) by RECIST 1.1. Archival tumor tissue and baseline (BL) and post-Tx plasma samples were collected for molecular analyses (reported elsewhere). Results: 133 pts were treated (median age: 62 y) and evaluated for safety, efficacy, and molecular correlative analysis. Dose reduction (31%) or Tx discontinuation (31%) occurred for toxicity. Median Tx duration was 112 days. The most common adverse events were hypertension 55% (Gr 3/4: 33%), fatigue 42% (Gr 3: 12.8%), diarrhea 35% (Gr 3: 5.3%), decreased appetite 35% (Gr 3: 2.3%), and nausea 32% (Gr 3: 3%); 1 pt had Gr 5 asthenia. Bowel obstruction, fistula formation, and perforation occurred in 3.8%, 2.3%, and 1.5%, respectively. Confirmed CR+PRs were observed in 19 pts (14.3%) by independent review (IRR) and 29 pts (21.8%) by investigator assessment (Inv). mPFS was 5.4 mos and mOS was 10.6 mos. Among 50 serum factors tested, only BL plasma Ang-2 correlated with maximal tumor shrinkage, R = 0.36 (Spearman), p < 0.001; ORR; PFS; and OS. The 24 pts with low BL Ang-2 plasma levels (cut-off value <2082 pg/mL) were compared with the 98 pts with high BL Ang-2 (>2082 pg/mL) and improved ORR (61% vs 18%), mPFS (9.5 vs 3.7 mos), and mOS (23 vs 8.9 mos) were observed. Conclusions: Lenvatinib in this population was tolerable and resulted in a 14.3% (IRR) and 21.8% (Inv) ORR and mOS of 10.6 mos.Low BL Ang-2 level appears to predict clinical benefit in a subset of pts with advanced EC who may achieve high response rates and prolonged overall survival. Further assessment is warranted. Clinical trial information: NCT01111461.
PTEN loss as a context-dependent determinant of patient outcomes in obese and non-obese endometrioid endometrial cancer patients.
Authors: Ju Zhenlin , Westin Shannon Neville , Broaddus Russell , Li Jie , Pal Navdeep , Lu Karen H. , Coleman Robert L. , Klempner Samuel , Cantley Lewis , Mills Gordon B. , Myers Andrea P. 
Published: March 2020

5521 Background: Aberrations in the PI3K pathway, the central relay pathway of insulin signals, occur in the majority of endometrioid endometrial cancers. We explored the prognostic utility of PIK3CA, PIK3R1, and PTEN mutations, as well as PTEN protein loss, in the context of patient weight. Methods: Patients (pts) treated for endometrial cancer at a single institution between 2000 and 2009 were identified. Tumor DNA was extracted and exome sequencing performed using a 454 platform with confirmation of hot spot mutations by Sequenom. PTEN protein expression was determined by immunohistochemistry and reverse phase protein array (RPPA). RPPA for 135 relevant proteins was performed using a GeneTAC arrayer to create spot arrays. Slides were scanned, analyzed, and quantitated using Microvigene software. Results: One hundred eighty seven endometrioid endometrial cancer specimens were included. Median age was 61 yrs and median body mass index (BMI) was 33.5 kg/m2. The majority of pts had early stage (I/II) disease (74%) and grade 2 tumors (66%). There were no statistically significant associations between progression free survival (PFS) and PIK3CA, PIK3R1, PTEN mutation or loss. However, when stratified by BMI, PTEN loss was associated with a significantly improved PFS (p< 0.006) in obese (BMI > 30 kg/m2) pts. In contrast, PTEN loss was associated with a worse PFS (p<0.06) in non-obese (BMI < 30 kg/m2) pts. Further, PTEN loss in obese and non-obese pts resulted in distinct protein changes by RPPA, with canonical PI3K pathway activation observed only in the non-obese PTEN loss cohort. PTEN loss in obese pts was associated with decreased expression of CATENIN and phosphorylated FOXO3A. Conclusions: These data suggest the impact of PTEN loss on tumor biology and clinical outcomes must be interpreted in the context of BMI and provide potential explanation for prior discrepant findings on effect of PTEN status on prognosis in endometrial cancer. These data describe a clinically important interaction between metabolic state and tumor genetics that could potentially unveil the biologic underpinning of obesity-related cancers and may be relevant to ongoing clinical trials with PI3K pathway inhibitors.