Risk Factors of Cardiotoxicity After Breast Cancer Radiation Therapy

Concern for cardiotoxicity after the treatment of breast cancer necessitates a better understanding of factors that may increase the risk of significant (grade ≥3) cardiac events. We investigated clinical factors, coronary artery calcium (CAC), and radiation therapy dose to cardiac structures as predictive post-radiation therapy cardiotoxicity risk factors.

We retrospectively analyzed a cohort of serial patients treated with neoadjuvant chemotherapy for stage I to III breast cancer from 2005 through 2014. We measured the incidence of cardiac events after treatment, adjusting for the competing risk of death.

We identified 174 patients with a median follow-up of 117 months and a median age of 47 years. The 10-year incidence of grade ≥3 cardiac events was 8.5% (95% CI, 4.7%-13.6%) with 13 events observed. 78.9% of the 166 patients with available imaging had no measurable CAC. Patients with nodal positivity (N = 75) were 3 times more likely to develop cardiac toxicity (HR=3.30) and were more likely to receive anthracyclines, hormonal therapy, and regional nodal irradiation during treatment (P < 0.05). After multivariable adjustment for age and smoking status, nodal positive disease remained associated with increased risk of significant cardiac events (P < .05).

In a cohort of patients with breast cancer with low CAC burden and overall low doses of radiation, we observed low rates of cardiotoxicity. However, our findings identify patients with nodal positive disease as a particularly high-risk group, suggesting that close follow-up and optimization of therapies for this subgroup is needed.