Response to progestin-based therapy in endometrial intraepithelial neoplasia: An exploratory biomarker study

Seay, Kieran, Hare, Maia, Cao, Jin, Katcher, Arielle, Akerman, Meredith, Beyaz, Semir, Goldberg, Gary L, Frimer, Marina (August 2026) Response to progestin-based therapy in endometrial intraepithelial neoplasia: An exploratory biomarker study. Gynecologic Oncology Reports, 66. p. 102134. ISSN 2352-5789

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Abstract

OBJECTIVE: With the incidence of endometrial intraepithelial neoplasia (EIN) rising among premenopausal women, fertility-sparing management with progestin-based therapy is increasingly utilized, yet a substantial proportion of patients fail to respond. This study explored associations between baseline tissue biomarker expression and response to progestin-based therapy in premenopausal women with EIN. METHODS: This was a single-institution retrospective cohort study of premenopausal women with EIN undergoing conservative management between March 2015 and December 2023. Immunohistochemical expression of progesterone receptor A (PR-A), progesterone receptor B (PR-B), and glucagon-like peptide-1 receptor (GLP-1R) was evaluated in pre-treatment and post-treatment endometrial biopsy specimens. Treatment response was dichotomized as complete response (CR) or progesterone resistance (PGR), defined as failure to achieve CR within 12 months of initiating progestin-based therapy. Associations between biomarker expression and treatment response were explored using descriptive and regression analyses. RESULTS: Endometrial biopsies were analyzed from 28 premenopausal patients prior to the initiation of progestin-based therapy. Baseline PR-A expression was significantly lower among non-responders in both glandular and stromal compartments. A pre-treatment PR-A:PR-B ratio ≤ 1 was associated with progesterone resistance in glandular tissue, whereas pre-treatment GLP-1R expression was not significantly associated with treatment response. Post-treatment glandular GLP-1R expression differed between groups, with a higher proportion of high expression observed among non-responders (54.6% vs. 6.7%, p = 0.021). CONCLUSION: In this exploratory cohort, baseline progesterone receptor expression patterns were associated with response to progestin-based therapy. These findings warrant validation in larger, prospective studies.

Item Type:	Paper
Subjects:	diseases & disorders > cancer diseases & disorders diseases & disorders > cancer > cancer types > endometrial cancer diseases & disorders > cancer > cancer types
CSHL Authors:	Beyaz, Semir
Communities:	CSHL labs > Beyaz lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	August 2026
Date Deposited:	23 Jun 2026 18:11
Last Modified:	23 Jun 2026 18:11
PMCID:	PMC13276136
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/42228

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