PROJECT SUMMARY
Nearly 20% of the 3 million breast cancer survivors in the U.S. have cardiovascular disease (CVD). The
National Cancer Institute, NHLBI, and professional oncology and cardiology societies have all endorsed the
importance of reducing CVD burden in breast cancer survivors through earlier recognition and intervention.
Although women diagnosed with stages I to III breast cancer have an excellent prognosis with 5-year relative
survival >90%, specific adjuvant therapies have been reported to lead to cardiovascular (CV) events that impair
health-related quality of life and/or lead to premature CVD death. CV events including acute myocardial
infarction, stroke, and venous thromboembolism have been reported to be associated with adjuvant
chemotherapy, biological agents, radiation therapy, and/or hormonal therapies. These treatment-related CV
events pose a significant public health problem because they will affect the increasing number of breast cancer
survivors’ health-related quality of life over a long-life expectancy. Currently, no standard risk model exists to
predict the risk of CV events associated with multiple adjuvant breast cancer therapies in the presence
of established CV risk factors (such as hypertension, hyperlipidemia, smoking) to inform practice
guidelines and promote shared clinical decision-making. Such models can inform women before treatment
about the potential risks of CVD from alternative treatment strategies while maintaining the best chances for
cancer cure. These models can also help to identify women at highest risk of CVD after therapy who would
potentially benefit from earlier and more intensive CV monitoring via routine imaging and/or use of preventive
medications to mitigate risk of CV events. To address this gap, our study will create risk prediction models by
analyzing a large, demographically heterogeneous cohort of adult women (N=40,500) with newly diagnosed
stages I to III invasive breast cancer in real-world health care settings. We will study women diagnosed from
2008-2020 and followed up to 15 years using the comprehensive electronic records of one of the largest health
plans in the U.S., Kaiser Permanente. In Aim 1, we will assess incident CV events (acute myocardial infarction,
stroke, heart failure) following adjuvant breast cancer therapies, adjusting for tumor characteristics and CVD risk
factors such as age, race/ethnicity, pre-existing CVD, CVD medications (statins, anti-hypertensives, anti-
diabetics), hypertension, diabetes, BMI, and smoking. We will then estimate whether the risk of CV events is
greater in the breast cancer cohort versus an age, race- matched cancer-free cohort. In Aim 2, we will create
and validate risk prediction models for early (<1 year) and late (up to 15 years) CV events. Our project will be
the first to estimate the association of multiple established CVD risk factors with the risk of breast cancer adjuvant
treatment-related CV events in a real-world, ethnically and socioeconomically diverse community-based cohort.
Our risk prediction models will provide new information to guide evidence-based clinical decision-making
concerning adjuvant therapy use for breast cancer and concurrent and post-treatment cardio-oncology care.