Polygenic risk of coronary artery disease for long-term survivors of breast cancer

Aim Cardiovascular disease is a leading cause of death for long-term breast cancer survivors. We evaluated whether a polygenic risk score for coronary artery disease (CAD-PRS) was associated with the risk of incident CAD for survivors of unilateral or contralateral breast cancer. Methods The study included 1,307 women with breast cancer first diagnosed at age <55 years who participated in the WECARE Follow-up Study. The CAD-PRS was based on a PRS developed and validated in a separate population. We modelled the association between incident CAD and the CAD-PRS, adjusting for age, CAD risk factors, first (and second) breast cancer treatment, study recruitment phase, and genetic population stratification. We also explored whether the risk of CAD depended on interactions between the CAD-PRS and cardiotoxic cancer treatment. Results There were 65 incident CAD diagnoses reported at a median of 16 years after breast cancer diagnosis. Participants with CAD-PRS≥median had a 2.48-times increased risk of CAD (95%CI = 1.44-4.29) relative to participants with CAD-PRS<median. Anthracycline-based chemotherapy was associated with increased CAD risk (HR = 2.04, 95%CI = 1.04-3.98), and the association was not modified by the CAD-PRS. The association between incident CAD and left-sided RT was increased for those with CAD-PRS≥median (HR = 2.90, 95% CI = 1.26-6.68), but not for those with CAD-PRS<median (HR = 0.96, 95% CI 0.32-2.88). There was evidence of super-additive interaction between the CAD-PRS and left-sided RT (relative excess risk due to interaction = 2.06, 95% CI 0.05-4.06). Conclusions A genome-wide CAD-PRS was associated with non-fatal CAD risk for long-term breast cancer survivors, providing potential utility for personalized cardiovascular care, particularly after RT.