Abstract
BackgroundAdvancements 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.MethodsWe 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.ResultsOver 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.ConclusionsThis 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.
Highlights
There were approximately 2.1 million new cases of incident female breast cancer in 2018 globally, accounting for 25% of cancer cases in women [1]
It seems likely that risk factors associated with coronary artery disease (CAD) in the general population will be associated with CAD in cancer survivors, but empirical evidence is needed, in those treated with chemotherapy or radiotherapy
There are currently no studies quantifying the performance of CAD PRS for risk prediction in breast cancer survivors and, whether polygenic risk scores interact with oncotherapy for breast cancer
Summary
There were approximately 2.1 million new cases of incident female breast cancer in 2018 globally, accounting for 25% of cancer cases in women [1]. While the consensus for the clinical utility of CAD PRS is still unclear [14,15,16,17], CAD PRS is potentially poised to add accuracy to clinical risk predictions, define populations who would most benefit from statin prescriptions, and estimate lifetime risk trajectories [18]. There are currently no studies quantifying the performance of CAD PRS for risk prediction in breast cancer survivors and, whether polygenic risk scores interact with oncotherapy for breast cancer. The aim of this study was to evaluate the association of a published coronary artery disease polygenic risk score [10] and incident CAD outcomes in a cohort of women with breast cancer. 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
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