Abstract P1-12-01: Impact of Anti-Estrogen Therapy on Early Vascular Referrals, Tests and Medications in Premenopausal Women with Operable Breast Cancer
Authors: Ansari Ahmer , Levine Beverly , Douglas Emily , Ansley Katherine , Melin Susan , Park Carolyn , Richardson Karl , D’Agostino Ralph , Jordan Jennifer , Thomas Alexandra 
Published: March 2023

Introduction: Premenopausal women with high-risk hormone receptor-positive (HR+) breast cancer (BC) undergo abrupt menopause induction with anti-estrogen therapy (AE) and ovarian function suppression (OFS). This treatment improves recurrence-free survival but may increase cardiovascular (CV) risk associated with early hypoestrogenemia. as observed in women with non-cancerous reasons for premature menopause. We sought to identify patterns of CV actions including referrals, tests and medication by type of AE therapy in premenopausal women in early follow-up for operable BC as a possible surrogate for early CV disease.

Methods: Consecutive premenopausal women ≤ 50 years (mean age 42.6 years; sd 5.9) with Stage I-III HR+ or triple negative breast cancer (TNBC) diagnosed between 02/2013-06/2020 were identified by retrospective review. Mean follow-up was 4.9 years (sd 2.1 years.) Women were placed into 3 treatment groups based on initial AE approach: HR+ on OFS+AE (HR+OFS), HR+ not on OFS (HRnoOFS), and TNBC. Patient demographics, cancer treatment and CV risk factors as well as post-diagnosis adverse CV events (myocardial infarction, transient ischemic attack) and CV-related clinical actions (CV actions) including referrals, (cardiology, neurology (vascular)), tests (stress test, angiogram, ECHO, EKG, Carotid US) and medications (statin, ACEi, ARB, betablocker, calcium channel blocker, antiarrhythmic, and anti-platelet agents) were recorded. For each CV outcome (events, total actions, referrals, tests, medications) we created an “any” vs “none” dichotomous variable as well as a variable for number of CV outcome per year of follow-up. Categorical variables were compared among the 3 groups using chi-square and Fisher’s exact tests; continuous outcomes (including the “per year” variables) were compared among the 3 groups using ANOVA. For the ANOVAs we report the global null hypothesis p-value. A two-tailed alpha of 0.05 was used throughout.

Results: 80, 78, and 48 (total n=206) women were identified in the HR+OFS, HRnoOFS and TNBC groups respectively. Mean follow-up was longest in the HRnoOFS group (Table 1). Mean number of CV actions per year were highest in the HR+OFS group compared with HRnoOFS and TNBC (0.41 vs 0.22 and 0.35, respectively; p=0.008.) The HR+OFS group had significantly more referrals during follow-up, as well as more referrals per year than the other two groups. This group also had significantly more tests per year than the other two groups. CV medication initiation did not differ among the groups. The proportion with &gt;3 CV actions during follow-up was 62% higher in women in the HR+OFS group compared to other groups. Experiencing &gt;3 CV actions was associated with having diabetes, hypertension, and hyperlipidemia, being a current smoker, and receipt of left-sided radiation (Table 2).

Conclusions: In this early follow-up period, women on OFS+AE experienced more CV actions per year suggesting concern for CV sequela in this patient group. Future work should seek to further understand the impact of OFS+AE on the CV health of premenopausal women, try to identify who is at greatest risk and test strategies to mitigate cardiotoxicity.

Table 1. Patient Characteristics and CV outcomes by Breast Cancer Treatment Group.

Table 2. Patient Characteristics by number of CV Actions.

Citation Format: Ahmer Ansari, Beverly Levine, Emily Douglas, Katherine Ansley, Susan Melin, Carolyn Park, Karl Richardson, Ralph D’Agostino, Jennifer Jordan, Alexandra Thomas. Impact of Anti-Estrogen Therapy on Early Vascular Referrals, Tests and Medications in Premenopausal Women with Operable Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-12-01.