Assessment of cardiovascular disease-associated mortality risk among early-stage breast cancer patients

Aim: Cardiovascular disease (CVD) is the most common non-cancer cause of death in breast cancer (BC) survivors, yet the age-specific point at which CVD deaths overtake BC deaths, and its early indicators, remain unknown. This study aimed to establish this time point and identify factors associated with cardiovascular-specific mortality (CSM) in early-stage BC. Methods: We analyzed 255,731 women diagnosed with stage I–III BC (2010–2020) from the Surveillance, Epidemiology, and End Results (SEER) 17 registries. CSM was compared with the general United States (US) female population using standardized mortality ratio (SMR) via Centers for Disease Control and Prevention’s Wide-ranging Online Data for Epidemiologic Research (CDC WONDER). Competing-risk methods estimated cumulative incidence, and Fine-Gray regression identified factors associated with CSM after adjustment for measured covariates. Results: Upon age standardization, the overall risk of CSM was modestly higher among BC patients than in the general female population [SMR = 1.16, 95% confidence intervals (CI): 1.13–1.19, P < 0.001], with marked heterogeneity by age; the relative excess was greatest in women aged < 50 (SMR = 2.894) and attenuated in older strata (50–59, SMR = 1.138; 60–69, SMR = 1.208; 70–85, SMR = 1.128). Cumulative CSM reached 2.53% at 84 months (7 years). Within the oldest cohort (70–85 years), cumulative CSM crossed above BC-specific mortality later, at approximately 8 years (97 months; 95% CI 91–101) [sub-distribution hazard ratio (SHR) = 19.37; 70–85 vs. 18–49], followed by unmarried status (1.59), Black race (1.37), advanced tumor (T4, 1.60) and nodal stage (N3, 1.34). Chemotherapy and radiotherapy were associated with lower CSM (SHR = 0.59 and 0.64); given SEER’s lack of treatment data, these likely reflect selection bias and residual confounding rather than protection. Conclusions: This is one of the first studies to identify an approximate mortality crossover point between CSM and BC-specific mortality at about 8 years (97 months) in women aged 70–85, providing a clinically relevant, exploratory time point for increased cardiovascular monitoring in this high-risk population.