Genomic risk prediction of coronary artery disease in women with breast cancer: a prospective cohort study

Abstract

Background Advancements in cancer therapeutics have resulted in increases in cancer-related survival; however, there is a growing clinical dilemma. The current balancing of survival benefits and future cardiotoxic harms of oncotherapies has resulted in an increased burden of cardiovascular disease in breast cancer survivors. Risk stratification may help address this clinical dilemma. This study is the first to assess the association between a coronary artery disease-specific polygenic risk score and incident coronary artery events in female breast cancer survivors. Methods We utilized the Studies in Epidemiology and Research in Cancer Heredity prospective cohort involving 12,413 women with breast cancer with genotype information and without a baseline history of cardiovascular disease. Cause-specific hazard ratios for association of the polygenic risk score and incident coronary artery disease (CAD) were obtained using left-truncated Cox regression adjusting for age, genotype array, conventional risk factors such as smoking and body mass index, as well as other sociodemographic, lifestyle, and medical variables. Results Over a median follow-up of 10.3 years (IQR: 16.8) years, 750 incident fatal or non-fatal coronary artery events were recorded. A 1 standard deviation higher polygenic risk score was associated with an adjusted hazard ratio of 1.33 (95% CI 1.20, 1.47) for incident CAD. Conclusions This study provides evidence that a coronary artery disease-specific polygenic risk score can risk-stratify breast cancer survivors independently of other established cardiovascular risk factors.

Pharmacogenomics for Prediction of Cardiovascular Toxicity: Landscape of Emerging Data in Breast Cancer Therapies

“…Genetic risk, however, most commonly constitutes of a combination of intermediate-and low-risk variants rather than a few high-risk genetic alterations [75], and risk prediction scores based on genome-wide association studies have been suggested to provide valuable information at the individual level [76]. A polygenic risk score including 1,745,180 variants was associated with higher risk of coronary artery disease in women with breast cancer, without baseline risk factors, even after adjustment for sociodemographic and medical confounders, including type of oncological treatment (HR 1.33; 95% CI 1.20-1.47) [77]. Among the 12,413 women included in this analysis, 38% had received adjuvant chemotherapy and 71% had received adjuvant radiotherapy.…”