PubMed abstract / permitted excerpt

IMPORTANCE: Although modern radiotherapy (RT) techniques have reduced cardiac exposure, concerns regarding RT-induced heart disease persist. Identifying which patients are most vulnerable to cardiac toxic effects is crucial for personalized survivorship care. OBJECTIVE: To evaluate whether the association between tumor laterality and ischemic heart disease (IHD) risk varies by cumulative baseline cardiovascular risk burden. DESIGN, SETTING, AND PARTICIPANTS: This retrospective nationwide cohort study used data on 23 305 women in the Korean National Health Insurance Service database who underwent postoperative RT for breast cancer without prior IHD from January 1, 2002, to December 31, 2018. The median follow-up was 4.3 years (IQR, 2.5-6.5 years); data analysis was completed in March 2023. EXPOSURES: Treatment laterality (left-sided vs right-sided RT) and baseline cardiovascular risk burden (defined as a count of 6 factors: age ≥55 years, obesity, smoking, hypertension, diabetes, and dyslipidemia). MAIN OUTCOMES AND MEASURES: The cumulative incidence of IHD was estimated using competing-risk analysis. Subdistribution hazard ratios (sHRs) were calculated using Fine-Gray models. RESULTS: Of 23 305 patients (mean [SD] age, 51.7 [9.2] years), 11 723 (50.3%) received left-sided RT and 11 582 (49.7%) received right-sided RT. Left-sided RT was associated with a statistically significant increase in IHD risk (sHR, 1.11; 95% CI, 1.01-1.22; P = .04). No statistically significant difference in IHD risk between left- and right-sided RT was observed among patients with 0 to 2 cardiovascular risk factors, whereas left-sided RT was associated with significantly higher IHD risk among patients with 3 risk factors (adjusted sHR, 1.37; 95% CI, 1.10-1.71; Gray test P = .004). CONCLUSIONS AND RELEVANCE: In this cohort study of 23 305 women with breast cancer, excess cardiac risk associated with left-sided RT was concentrated among patients with 3 cardiovascular risk factors. These findings suggest that among patients with low baseline risk profiles, the difference in IHD risk between left- and right-sided treatment may be small, whereas those with high cardiovascular burden warrant prioritized access to advanced heart-sparing modalities and aggressive risk factor management.