PROJECT SUMMARY / ABSTRACT Breast cancer survivors are at high risk of developing and dying from cardiovascular disease (CVD) following breast cancer diagnosis, but subpopulations at increased risk and targets for intervention have not been well- characterized. A growing body of literature links CVD with specific cardiotoxic cancer treatments. CVD risk among breast cancer survivors might vary by concomitant non-adherence to CVD medications and presence of CVD risk factors. However, most of the studies on CVD risk among breast cancer patient populations have had significant limitations, including poorly characterized CVD outcomes, lack of CVD medication adherence data and risk factors, and poorly matched cancer-free control groups. Well-designed studies are needed to identify subpopulations of breast cancer survivors at high risk for CVD events and modifiable targets for intervention while accounting for specific breast cancer treatments received, CVD medications, and CVD risk factors. We propose to conduct an ancillary study within an ongoing study of breast cancer survivors which will overcome limitations of prior studies. The proposed study will comprehensively examine clinical and behavioral predictors of CVD outcomes among breast cancer survivors, and will maximize unique patient and data resources available at Kaiser Permanente Northern California (KPNC). We will compare CVD events in the Pathways Study, a cohort of female KPNC members age ?21 years diagnosed with invasive breast cancer (n=4,453, R01CA105274) with CVD events in a new age, race/ethnicity, history of comorbidity, and length of KPNC membership matched cohort of healthy KPNC female members (n=22,265). Specific aims are: Aim 1) To examine the absolute risk and relative risk of incident CVD events (ischemic heart disease, stroke/transient ischemic attack, and cardiomyopathy/heart failure, and others) and new onset CVD risk factors (hypertension, diabetes, dyslipidemia) in women with breast cancer (Pathways) and a cancer-free comparison group (KPNC matched cohort); Aim 2) In women with a history of breast cancer (Pathways), to examine the relative risk of incident CVD events and new onset of CVD risk factors, by type of cardiotoxic breast cancer treatment received, including chemotherapy/biologic therapy (anthracyclines, trastuzamab), hormonal therapy (Tamoxifen, aromatase inhibitors), and radiation therapy, controlling for confounders related to baseline CVD medication adherence, clinical and behavioral risk factors, medical care and health care system factors, and socioeconomic status (SES); Aim 3) To assess adherence to CVD medications in women with a history of breast cancer (Pathways) using 14 years of follow-up data, and to examine the association of adherence with risk of CVD events controlling for cardiotoxic cancer treatment received, baseline CVD clinical and behavioral risk factors, medical care and health care system factors, and SES. Impact: Results from this study will have important implications for identifying breast cancer subgroups at high risk of CVD and identifying potential targets for intervention, such as medication adherence and control of CVD risk factors.