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

To investigate the association of molecular subtype with progesterone response in patients with endometrial cancer (EC) or atypical endometrial hyperplasia (AEH). Premenopausal 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. Of 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). Molecular 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. • In endometrial cancer/atypical endometrial hyperplasia (AEH), molecular subtype may be associated with progesterone response. • Molecular classification may help guide selection for progestin-based treatments in patients with endometrial cancer/AEH. • Response to progestin varied among molecular subtypes of endometrial cancer. • Copy number-low tumors showed the highest response rate to progestin-based treatments. • Close follow-up is warranted for patients with complete response due to high risk of recurrence. [ABSTRACT FROM AUTHOR]

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