Endometrial cancer risk management in patients with Lynch syndrome at a tertiary community cancer center.

Abstract

e22539 Background: Lynch syndrome (LS) is a genetic predisposition associated with germline alterations in the DNA mismatch repair pathway that increases the risk of endometrial cancer (EC) up to 10-fold among other cancer risks. Hysterectomy (H) is a definitive strategy for risk reduction offered after childbearing. Screening for EC with an endometrial biopsy (EMB) is a strategy for those who are not ready for surgery. However, the uptake and utility of EMB are unknown. We present data from a large retrospective cohort aiming to provide insight into these questions. Methods: We reviewed the EC risk management behaviors for 75 assigned females at birth with LS between 2006 and 2024 at a large tertiary community cancer center in Seattle, WA. Data collected include age, pathogenic variant (PV), personal and family history of cancer, gynecologic surgical history, EMB, and pathology findings at EMB and/or surgery. Results: Median age of the cohort at LS diagnosis was 44 years (21-87), and 42 and 33 patients were pre- and post-menopausal, respectively. Reasons for genetic testing included: diagnosis of LS-related cancer (n = 37), familial testing (n = 17), and family history of cancer (n = 21). 18 patients had a PV in MLH1, 21 in MSH2 , 21 in MSH6 , and 15 in PMS2 . Of the 75 patients, 44 (59%) had either H + bilateral salpingectomy (H-BS) or H + bilateral salpingo-oophorectomy (H-BSO) before (n = 14) or at LS diagnosis (n = 30); 19/44 had EC and all had H-BSO. Longitudinal follow-up information was available for the remaining 31 patients with a median follow-up time of 5.48 years (0.03, 18.62). 27/31 patients were older than 30 at some point during follow-up and were considered eligible for EMB. Nine patients underwent EMB (33%), including 2 patients who had the procedure immediately prior to surgery. One patient was found to have a precursor lesion on EMB and EC was found on subsequent H-BS. At the time of LS diagnosis, 45 patients had both a uterus and no diagnosis of EC. 25/45 patients (56%) underwent risk reducing surgery, 3 chose a H-BS and 22 H-BSO. No ovarian abnormalities were noted. There was trend favoring ovarian conservation in women aged < 45 (p = 0.1, Fisher’s exact test). No differences were observed based on the gene involved. Of the 19 patients that chose to forego surgery,15 were eligible for screening, but only 4 (27%) patients underwent EMB. Conclusions: H-BSO is the most common EC risk reduction strategy in patients with LS. Receipt of a BSO is common and similar across mismatch repair genes. Uptake of EMB is low and a substantial fraction of at-risk patients don’t receive any EC risk management strategies. Further research is needed to identify patient and provider-specific factors contributing to the observed variation in risk management.