Molecular subtyping in endometrial cancer: A promising strategy to guide fertility preservation Journal Article
| Authors: | Dagher, C.; Manning-Geist, B.; Ellenson, L. H.; Weigelt, B.; Rios-Doria, E.; Barry, D.; Abu-Rustum, N. R.; Leitao, M. M. Jr; Mueller, J. J. |
| Article Title: | Molecular subtyping in endometrial cancer: A promising strategy to guide fertility preservation |
| Abstract: | Objectives: To investigate the association of molecular subtype with progesterone response in patients with endometrial cancer (EC) or atypical endometrial hyperplasia (AEH). Methods: 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. Results: 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). Conclusion: 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. © 2023 Elsevier Inc. |
| Keywords: | adult; clinical article; controlled study; human tissue; treatment outcome; treatment response; retrospective studies; unclassified drug; gene mutation; genetics; cancer recurrence; drug withdrawal; paclitaxel; adjuvant therapy; comparative study; cancer staging; follow up; endometrial cancer; endometrial neoplasms; endometrium cancer; disease association; carboplatin; multiple cycle treatment; cohort analysis; genetic association; pathology; retrospective study; cryopreservation; microsatellite instability; premenopause; molecular biology; mismatch repair protein; protein msh6; endometrium tumor; mismatch repair protein pms2; megestrol acetate; oocyte retrieval; fertility preservation; levonorgestrel; copy number variation; progesterone; infertility therapy; endometrial hyperplasia; endometrium hyperplasia; molecular subtype; atypical endometrial hyperplasia; time to treatment; fertility sparing; humans; human; female; article; pembrolizumab; polymerase epsilon; dna mismatch repair protein msh2 |
| Journal Title: | Gynecologic Oncology |
| Volume: | 179 |
| ISSN: | 0090-8258 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2023-12-01 |
| Start Page: | 180 |
| End Page: | 187 |
| Language: | English |
| DOI: | 10.1016/j.ygyno.2023.11.006 |
| PUBMED: | 37992549 |
| PROVIDER: | scopus |
| PMCID: | PMC10843754 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Jennifer J. Mueller -- Source: Scopus |
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641Weigelt -
186Mueller -
109Ellenson -
35Rios-Doria -
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Dagher
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