(007) The Safety of Vaginal Estrogen Therapy for Genitourinary Syndrome of Menopause in Women with a History of Breast Cancer – A Claims Database Analysis
Authors: Agrawal P , Dumas K , Singh S , Kohn J , Kohn T , Clifton M 
Published: May 2023

Abstract

Introduction
Systemic treatment for breast cancer (BC) may result in genitourinary syndrome of menopause (GSM) in up to 70% of postmenopausal BC survivors. Though systemic estrogen therapy is usually avoided in these patients, vaginal estrogen therapy may be prescribed to treat GSM symptoms. However, few eligible patients with GSM and history of BC are prescribed vaginal estrogen due to concern for cancer recurrence.

Objective
Our objective was to assess the recurrence rates of BC by vaginal estrogen therapy status in women diagnosed with GSM with a history of BC using a large US claims database.

Methods
A US health research network (the TriNetX Diamond Network) of over 200 million patients was queried from 2009 to 2022. Females with a diagnosis of BC (C50, Z86.000) within the five years before an initial GSM diagnosis (ICD-10 N90.5, N95.2) were included. Patients who underwent mastectomy (1015054), radiation oncology treatment (1010843), and/or chemotherapy (1002) within three months prior to the diagnosis of GSM were excluded as they were considered to have active disease. Recurrence was defined as the need for mastectomy, radiation, or chemotherapy within three months to five years after initiating vaginal estrogen therapy for GSM. We excluded women diagnosed with cancers other than BC in the 5 years prior to or after their initial GSM diagnosis. The study cohort included those with ≥3 vaginal estrogen (GU500) prescriptions, while the control cohort only included women without vaginal estrogen prescriptions. Propensity-matching between the cohorts for age, ethnicity, race, family history of breast neoplasm (Z80.3), overweight and obesity (E66), hormone replacement therapy (Z79.890), and tobacco usage (Z72.0) was conducted. A sub-analysis by positive estrogen receptor (+ER) status (Z17.0), when available, was performed.

Results
Amongst females with GSM following a history of BC, 2,113 (5%) received ≥3 vaginal estrogen prescriptions, while 40,019 patients (95%) didn’t receive any vaginal estrogen prescriptions. Amongst those with a +ER status, 410 females (3.9%) received ≥3 vaginal estrogen prescriptions, while 10,182 (96.1%) didn’t receive any vaginal estrogen prescriptions. Compared to matched controls, females with ≥3 vaginal estrogen prescriptions (n=2,111) had similar risks of mastectomy procedures (relative risk (RR) 1.06 [95% CI 0.54, 2.06]), chemotherapy (RR 1.16 [0.98, 1.37]), and radiation treatment (RR 1.06 [0.54, 2.11]) within three months to five years following the first estrogen prescription (Table 1). Individuals with a +ER status and ≥3 vaginal estrogen prescriptions (n=409) had a similar risk of mastectomy procedures, chemotherapy, or radiation treatment (RR 1.07 [0.86, 1.33]) within three months to five years following the first prescription compared to matched controls (Table 1).

Conclusions
In this large claims-based analysis, we found similar risks of mastectomy, chemotherapy, and radiation treatment, which serve as proxies for recurrence, after the use of vaginal estrogen for GSM in women with a personal history of BC within the five years prior to their GSM diagnosis. These results suggest that vaginal estrogen therapy in women with GSM and history of BC is not associated with an increased risk of BC recurrence and may hence be safe.

Disclosure
No