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Background The Cancer Genome Atlas identified four molecular subgroups of endometrial cancer with survival differences based on whole genome, transcriptomic, and proteomic characterization. Clinically accessible algorithms that reproduce this data are needed. Our aim was to determine if targeted sequencing alone allowed for molecular classification of endometrial cancer. Methods Using a custom-designed 156 gene panel, we analyzed 47 endometrial cancers and matching non-tumor tissue. Variants were annotated for pathogenicity and medical records were reviewed for the clinicopathologic variables. Using molecular characteristics, tumors were classified into four subgroups. Group 1 included patients with > 570 unfiltered somatic variants, > 9 cytosine to adenine nucleotide substitutions per sample, and MSH2, MSH6, MLH1, PMS2. Group 3 included patients with TP53 mutations without mutation in mismatch repair genes. Remaining patients were classified as group 4. Analyses were performed using SAS 9.4 (SAS Institute Inc., Cary, North Carolina, USA). Results Endometrioid endometrial cancers had more candidate variants of potential pathogenic interest (median 6 IQR 4.13 vs. 2 IQR 2.3; p PTEN (82% vs. 15%, p PIK3CA (74% vs. 23%, p TP53 (18% vs. 77%, p POLE mutations, most commonly P286R and V411L. Of the grade 3 endometrioid carcinomas, those with POLE mutations were less likely to have risk factors necessitating adjuvant treatment than those with low tumor mutational burden. Targeted sequencing was unable to assign samples to microsatellite unstable, copy number low, and copy number high subgroups. Conclusions Targeted sequencing can predict the presence of POLE mutations based on the tumor mutational burden. However, targeted sequencing alone is inadequate to classify endometrial cancers into molecular subgroups identified by The Cancer Genome Atlas.

Objective Endometrial cancer survivors are the least physically active of all cancer survivor groups and exhibit up to 70% obesity. While studies suggest lifestyle interventions result in improved health outcomes, recruitment and availability of these programs are limited. The purpose was to evaluate the acceptability and validity of the Fitbit Alta™ physical activity monitor (Fitbit) for socioculturally diverse endometrial cancer survivors. Methods Thirty endometrial cancer survivors were given wrist-worn Fitbits to wear for 30 days. Participants then returned the Fitbits, completed the Godin Leisure-Time Exercise Questionnaire (GLTEQ), Technology Acceptance Questionnaire, and answered qualitative prompts. Correlations between daily Fitbit step counts, demographic factors, body mass index (BMI), and GLTEQ Index, were analyzed using Stata 13.0. Concordance Correlation Coefficient using U statistics was used to examine convergent validity. Results Twenty-five participants completed the study. Mean age was 62 ± 9 years. Mean BMI was 32 ± 9 kg·m −2 . Self-identified race/ethnicity was 36% Hispanic, 36% non-Hispanic white, 16% non-Hispanic black and 12% Asian. Participants wore the Fitbits a median of 93% of possible days. Median daily Fitbit step count was 5325 (IQR: 3761–8753). Mean Technology Acceptance score was 2.8 ± 0.5 out of 4.0. Younger ( p p = 0.99) between step count and GLTEQ Index. Most free responses reflected positive experiences. Conclusions The Fitbits were well accepted in this sample. Self-reported physical activity was not associated with steps recorded. The physical activity data indicate an insufficiently active population.

// Eirwen M. Miller 2 , Nicole E. Patterson 1 , Jenna Marcus Zechmeister 2 , Michal Bejerano-Sagie 1 , Maria Delio 1 , Kunjan Patel 1 , Nivedita Ravi 1 , Wilber Quispe-Tintaya 1 , Alexander Maslov 1 , Nichelle Simmons 1 , Maria Castaldi 1 , Jan Vijg 1 , Rouzan G. Karabakhtsian 3 , John M. Greally 1 , Dennis Y.S. Kuo 2 and Cristina Montagna 1 1 Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA 2 Department of Obstetrics & Gynecology and Women’s Health, Division of Gynecologic Oncology, Montefiore Medical Center, Bronx, NY 10461, USA 3 Department of Pathology, Montefiore Medical Center, Bronx, NY 10461, USA Correspondence to: Cristina Montagna, email: cristina.montagna@einstein.yu.edu Keywords: target sequencing; next generation sequencing; endometrial carcinoma; tumor recurrence Received: July 29, 2017 Accepted: September 08, 2017 Published: October 26, 2017 ABSTRACT Next generation sequencing (NGS) technologies have revolutionized our approach to genomic research. The use of whole genome sequencing (WGS), whole exome sequencing (WES), transcriptome profiling, and targeted DNA sequencing has exponentially improved our understanding of the human genome and the genetic complexities underlying malignancy. Yet, WGS and WES clinical applications remain limited due to high costs and the large volume of data generated. When utilized to address biological questions in basic science studies, targeted sequencing panels have proven extremely valuable due to reduced costs and higher sequencing depth. However, the routine application of targeted sequencing to the clinical setting is limited to a few cancer subtypes. Some highly aggressive tumor types, like type 2 endometrial cancer (EC), could greatly benefit from routine genomic analysis using targeted sequencing. To explore the potential utility of a mid size panel (~150 genes) in the clinical setting, we developed and validated a custom panel against WGS, WES, and another commercially available targeted panel. Our results indicate that a mid size custom designed panel is as efficient as WGS and WES in mapping variants of biological and clinical relevance, rendering higher coverage, at a lower cost, with fewer variants of uncertain significance. Because of the much higher sequencing depth that could be achieved, our results demonstrate that targeted sequencing outperformed WGS and WES in the mapping of pathogenic variants in a breast cancer case, as well as a case of mixed serous and high-grade endometrioid EC, the most aggressive EC subtype.

Obesity confers an overall increased risk for development of endometrial cancer. However there are conflicting reports regarding the effect of obesity on patients' overall and disease specific survival. The purpose of this study was to evaluate the effect of obesity on survival in women with endometrial cancer.After IRB approval, records of women with diagnosis and treatment of endometrial cancer from 1999 to 2016 were abstracted for histopathological, treatment and demographic data. Death was confirmed by query of the Social Security Death Index. Kaplan Meier survival curves and Cox regression modeling was performed with Stata version 14.0.Of 1732 evaluable patients, there were significant differences in age at diagnosis, histology (endometrioid versus non-endometrioid), stage, race, grade, hypertension, hyperlipidemia, diabetes, and treatment between normal weight, overweight, obese, and morbidly obese patients (p 0.01). There was a linear association of younger age at diagnosis with increasing obesity (p 0.01) RObesity is associated with younger age at diagnosis and earlier stage disease. Obesity is associated with improved disease specific survival for stage 3 and 4 non-endometrioid endometrial cancers.

Objective: The objective of this study is to assess the outcome of port-a-cath (PAC) maintenance every three months in patients with gynecologic malignancies with the goal of standardizing a safe and appropriate interval that would maintain patency and minimize side effects. Methods: We performed a retrospective medical record review and evaluation of all patients with a Bard? PAC who were noted to have no evidence of disease (NED) during the years 2003 to 2010. The interval between accessions and any complications related to the presence of the PAC were recorded. Relevant complications included skin infections, bacteremia, thrombosis, and occlusions. Statistical analysis was done using the Fisher’s exact test. Results: A total of 201 patients had PAC placed and 43 patients underwent PAC accessions to maintain patency. The total number of accessions was 150 with a median number per patient of 2.0 (range 1 - 10). The mean time between flushes was 112 days (SD = 57). When comparing women in maintenance who had flushes within 90 days versus those who had flushes over 90 days apart, there was no difference in infection or occlusion rates between these groups (p = 0.515). In the Conclusion: Infections and occlusions are rare in women with gynecologic malignancies undergoing maintenance of their PAC. Longer intervals between PAC flushes do not appear to affect the outcome in our patients. Our ongoing data and follow-up confirm that extending the interval of PAC accession to every 3 months, rather than monthly, is safe, effective and convenient in the patient population with gynecologic malignancies.

Objectives: Dysbiosis is thought to promote endothelial dysfunction and chronic inflammation, resulting in many chronic human diseases including cancer. This pilot study sought to characterize the cervicovaginal, endometrial and anorectal micro- and mycobiota of post-menopausal women with endometrioid endometrial adenocarcinoma (EAC), uterine serous carcinoma (USC), and controls without cancer. Methods: Post-menopausal patients undergoing hysterectomy for endometrial cancer or non-cancerous disease were enrolled after informed consent. Women were excluded if they reported history of prior cancer, recent urinary or gynecologic infection, antibiotic or probiotic use. Microbial swabs were obtained from the cervicovaginal, the anorectal, and the endometrial cavity after removal of the uterus. DNA was extracted and PCR amplified using barcoded 16SV4 (bacterial) and ITS1 (fungal) primers. Next generation libraries were prepared and sequenced on an Illumina MiSeq 2x300. Sequence reads were processed using our internally developed bioinformatics pipeline and publically available software. Results: Next-generation sequencing of bacterial and fungal DNA revealed substantial differences of cervicovaginal, endometrial and anorectal microbiota in patients with USC (n= 8) compared to those with EAC (n= 13) or benign disease (n= 6). Uterine fungal reads were much higher in patients with USC than EAC (average of 3237 reads versus 938 reads respectively, p = 0.05 Wilcox test). Candida species were reduced, but not eliminated in cervicovaginal samples, and there was a dominance of Malassezia restrica in USC and EAC. A non-significant predominance of Porphyromonas species was noted in USC specimens compared to EAC specimens (p = 0.063). Conclusions: Alpha-diversity of 16S bacterial rRNA and fungal species of the cervicovaginal microbiome was significantly associated with endometrial cancer in our study. USC had a fundamentally different microbiome from control samples and demonstrated a predominance of Porphyromonas species. Further sampling and analysis is needed to confirm these results and to identify rare pathogens. Characterization of microbiota in women with endometrial cancer may help identify risk factors for gynecologic malignancy, and drive investigation regarding preventative and therapeutic intervention. Citation Format: Gregory M. Gressel, Marina Frimer, Christine P. Zolnik, Mykhaylo Usyk, Devin T. Miller, Eirwen M. Miller, D. Y.S. Kuo, Robert D. Burk. Characterization of the cervicovaginal, endometrial and anorectal microbiota and mycobiota of post-menopausal women with endometrioid and serous endometrial cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5143.