Cardiovascular Risk of Adjuvant Endocrine Therapy Plus Ovarian Suppression in Premenopausal Women with Breast Cancer: A Meta-Analysis of Randomized Controlled Trials

Introduction Adjuvant endocrine therapy with aromatase inhibitors (AIs) or selective estrogen receptor modulators (SERMs), combined with ovarian suppression (OS), improves survival in premenopausal women with hormone receptor–positive breast cancer. However, profound estrogen deprivation may adversely affect cardiovascular health. In postmenopausal women, AIs are associated with a higher risk of cardiovascular events compared with SERMs. In contrast, cardiovascular outcomes in premenopausal trials have been reported primarily as adverse events and remain underpowered for definitive safety assessment. Whether adjuvant AI plus OS confers excess cardiovascular risk compared with SERM-based therapy in premenopausal women remains uncertain. Purpose To compare cardiovascular outcomes associated with AIs plus OS versus SERMs with or without OS in premenopausal women with hormone receptor–positive breast cancer. Methods We conducted a systematic search of PubMed, Embase, and the Cochrane Library to identify studies comparing AIs plus OS versus SERMs with or without OS in premenopausal women with hormone receptor positive breast cancer. Outcomes were arrhythmia, cardiac ischemia or myocardial infarction, stroke, hypertension, and thrombosis. Pooled risk ratios (RRs) with corresponding 95% confidence intervals (CIs) were calculated using random-effects models. Statistical heterogeneity was assessed using the I² statistic. A two-sided P-value < 0.05 was considered statistically significant. Results We included four randomized controlled trials, with a total of 7,534 premenopausal women with hormone receptor positive breast cancer, of whom 3,958 (53%) received AIs in addition to OS. Among studies reporting median age, the median was 45 years, and the median follow-up duration ranged from 47 to 68 months. Compared with SERMs with or without OS, treatment with AIs plus OS was associated with a significantly increased risk of cardiac ischemia or myocardial infarction (RR, 2.32; 95% CI, 1.13–4.76; I² = 0%; P = 0.02). No significant differences were observed between groups for arrhythmia (RR, 0.87; 95% CI, 0.51–1.49; I² = 0%; P = 0.62), hypertension (RR, 1.05; 95% CI, 0.95–1.16; I² = 5%; P = 0.37), stroke (RR, 0.60; 95% CI, 0.35–1.03; I² = 0%; P = 0.06), or thrombosis (RR, 0.31; 95% CI, 0.09–1.06; I² = 16%; P = 0.06). Conclusions In premenopausal women with hormone receptor–positive breast cancer, AIs combined with OS were associated with an increased risk of cardiac ischemia or myocardial infarction compared with SERM-based therapy, without differences in other cardiovascular outcomes. These findings underscore the importance of cardiovascular risk assessment in this population.