Molecular subtyping in endometrial cancer: A promising strategy to guide fertility preservation

Abstract

ObjectivesTo investigate the association of molecular subtype with progesterone response in patients with endometrial cancer (EC) or atypical endometrial hyperplasia (AEH). MethodsPremenopausal patients aged ≤48 years with tumor-normal sequencing data who received progesterone for EC/AEH from 1/1/2010–6/30/2021 were identified. Tumors were classified as POLE-ultramutated, microsatellite instability-high (MSI-H), copy number-high (CN-H), or copy number-low (CN-L) molecular subtype. Best response to progesterone was compared by subtype. Appropriate statistical tests were performed. ResultsOf 20 patients, 7 (35%) had AEH and 13 (65%) had EC. Sixteen tumors (80%) were CN-L, 3 (15%) were MSI-H, and 1 (5%) was POLE-ultramutated. Median time on progesterone was 22 months (range, 3–115). Ten patients (50%) had complete response (CR); median time to CR was 9 months (range, 3–32). Four patients (20%) had stable disease (SD) and 6 (30%) had progressive disease (PD). For CN-L tumors, 10 patients (62%) had CR, 3 (19%) had SD, and 3 (19%) had PD. For MSI-H tumors, 1 patient (33%) had SD and 2 (66%) had PD. For POLE-ultramutated tumors, 1 patient had PD. Median follow-up was 48 months (range, 12–123). Four of 10 patients (40%) with CR recurred; median time from CR to recurrence was 16 months (range, 5–102). ConclusionMolecular subtype may be associated with progesterone response in patients with EC/AEH. CN-L tumors had the best response, and MSI-H tumors had the poorest. Recurrence after CR is common, and close surveillance is warranted. Larger studies investigating the role of molecular classification in medical management of EC/AEH are needed.