Thanks to advances in breast cancer treatments, there are more than 3.8 million survivors of female breast cancer. Women with invasive breast cancer have a 5-year survival rate of 90%. Although there are decreased rates of breast cancer-specific mortality, there has been an increase in cardiovascular and cerebrovascular disease-specific mortality in women with a history of breast cancer. Unfortunately, cardiovascular disease (CVD) is currently the number one cause of death in the US among women. Therefore, it’s a major health concern, especially among breast cancer survivors. Factors behind the increased risk of CVD in this population are poorly understood but some evidence points to the way breast cancer is treated. Several breast cancer therapies are known to be cardiotoxic; however, very few studies have examined CVD risk among women with and without a history of breast cancer. Population-based research could aid in quantifying the risk of CVD burden among the two groups. The objective of the Pathways Heart Study, co-led by Dr. Heather Greenlee from Fred Hutch Division of Public Health Sciences and Dr. Marilyn Kwan from Kaiser Permanente Northern California Division of Research, is to quantify the risk of CVD incidence and death among women with breast cancer relative to women without breast cancer over a follow-up of up to 14 years overall and according to the cancer treatment they received. “In addition to monitoring for disease, we need to identify ways to prevent the increased cardiovascular risk from the outset and identify the populations at highest risk. This risk can potentially be reduced with new and less cardiotoxic drugs, drugs to block the cardiovascular toxicities, and possibly lifestyle modifications,” explained Dr. Greenlee. The study is published in the Journal of Clinical Oncology.
The Pathways Heart Study is a prospective cohort study located within the Kaiser Permanente Northern California (KPNC) integrated health system. The overall goal of the Pathways Heart Study is to evaluate CVD and cardiometabolic risk factors in women with breast cancer. Covariate data (sociodemographic and other factors) were collected from electronic health records. Data on breast cancer therapies such as chemotherapy, radiation therapy and endocrine therapy were obtained from KPNC Cancer Registry. Chemotherapy exposure variables included anthracyclines including the frequently prescribed doxorubicin (Adriamycin ®) and trastuzumab (Herceptin ®); two drugs known to be cardiotoxic. In the analysis, four chemotherapy exposure groups were created: (1) anthracyclines without trastuzumab, (2) anthracyclines with trastuzumab, (3) trastuzumab without anthracyclines, and (4) neither anthracyclines nor trastuzumab. The primary CVD outcomes in this study included ischemic heart disease, heart failure, cardiomyopathy, and stroke. Secondary CVD outcomes included arrhythmia, cardiac arrest, carotid disease, myocarditis/pericarditis, transient ischemic attack, valvular disease, and venous thromboembolism (VTE). There was a total of 13,642 breast cancer cases and 68,202 matched case controls. Cox proportional hazards models were utilized to examine the primary and secondary CVD outcomes among breast cancer cases and matched controls without breast cancer.
During a follow-up time of 7 years, women with breast cancer had a higher incidence of mortality from heart failure, cardiomyopathy, stroke, arrythmia, cardiac arrest, and VTE. Women with a history of anthracycline use had higher incidence of heart failure and cardiomyopathy. Anthracycline is dose-dependent and can yield irreversible damage. Women with anthracycline exposure had the highest risk of arrhythmia and there was a 3-fold risk for VTE in all chemotherapy groups. Dr. Greenlee and colleagues also reported a higher risk of CVD-related and all-cause mortality with all groups, except in the anthracycline and trastuzumab group.
The Pathways Heart Study included a large sample of breast cancer cases and analyzed a racially and ethnically diverse patient population. “Using 14 years of data from the KPNC electronic health record, we showed that multiple forms of breast cancer treatments, including specific forms of chemotherapy, radiation therapy, and endocrine therapies, increase risk of multiple forms of cardiovascular disease”, said Dr. Greenlee. Overall, this study reported that women with breast cancer had a higher risk of developing CVD compared to women without breast cancer. CVD risks were different among chemotherapy groups. With compassion Dr. Greenlee noted, “We don’t want these findings to dissuade women from seeking treatment for their breast cancer. Rather, we want this to be a call to action for oncology, cardiology and primary care teams to establish robust clinical pathways to monitor and effectively treat cardiovascular disease.” Dr. Greenlee concluded by saying, “[u]ltimately, our findings support the need to raise awareness that this population of women is at increased risk of cardiovascular disease, and robust, comprehensive clinical pathways need to routinely monitor and manage any future cardiovascular disease.”
Cancer Consortium members Heather Greenlee and Richard Cheng from the UW/Fred Hutch CardioOncology program, contributed to this work.
Greenlee H, Iribarren C, Rana JS, Cheng R, Nguyen-Huynh M, Rillamas-Sun E, Shi Z, Laurent CA, Lee VS, Roh JM, Santiago-Torres M, Shen H, Hershman DL, Kushi LH, Neugebauer R, Kwan ML. Risk of Cardiovascular Disease in Women With and Without Breast Cancer: The Pathways Heart Study. Journal of Clinical Oncology. 2022 May 20;40(15):1647-58.