Prognostic Biomarker of Fertility-Preserving Hormonal Therapy Based on Multigene Panel Testing for Endometrial Cancer

Area of Science:

• Oncology
• Genetics
• Reproductive Medicine

Background:

• Fertility-preserving treatments are crucial for women with early-stage endometrial cancer or hyperplasia.
• Medroxyprogesterone acetate (MPA) is a common hormonal therapy, but predicting treatment response can be challenging.
• Identifying biomarkers can optimize patient selection and treatment strategies.

Purpose of the Study:

• To identify prognostic biomarkers for predicting treatment outcomes in patients receiving fertility-preserving high-dose medroxyprogesterone acetate (MPA) therapy.
• To correlate specific gene mutations with treatment response, duration to tumor disappearance, and recurrence-free survival.
• To explore the utility of comprehensive multigene panel testing in this patient population.

Main Methods:

• Genomic DNA was extracted from formalin-fixed paraffin-embedded samples of 38 patients (20 atypical endometrial hyperplasia, 18 stage IA G1 endometrial cancer).
• PleSSision-Rapid multigene panel testing was performed to analyze actionable gene mutations.
• Treatment outcomes including complete response (CR), stable disease (SD), progressive disease (PD), duration to tumor disappearance, and recurrence-free survival (RFS) were assessed.

Main Results:

• 82% of patients achieved complete response (CR) to MPA therapy.
• The most frequent mutations were PTEN (68.4%), CTNNB1 (55.2%), and PIK3CA (33.3%).
• PTEN mutations correlated with a longer duration to tumor disappearance (p=0.011), while PIK3CA mutations in atypical endometrial hyperplasia (AEH) were linked to shorter RFS (p=0.048).

Conclusions:

• Genetic alterations, particularly PTEN and PIK3CA mutations, are significantly associated with treatment outcomes in patients receiving MPA therapy.
• These mutations show potential as prognostic biomarkers for predicting response and recurrence.
• Multigene panel testing can aid in personalizing fertility-preserving treatment strategies for endometrial conditions.