In an analysis from the prospective cohort Pathways Heart Study reported in the Journal of Clinical Oncology, Heather Greenlee, ND, PhD, and colleagues found that breast cancer survivors were at increased risk of cardiovascular disease and mortality compared with women without breast cancer, with risks differing according to treatments received.
Heather Greenlee, ND, PhD
Study Details
In the study, 13,642 women with a diagnosis of invasive breast cancer between 2005 and 2013 were matched 1:5 on birth year and race/ethnicity with 68,202 control women without breast cancer from the Kaiser Permanente Northern California membership. Cancer treatment, cardiovascular disease outcomes, and covariate data were obtained from electronic health records.
Key Findings
Average follow-up was 7 years (range = 1–14 years). On multivariate analysis, patients with breast cancer who received anthracyclines without trastuzumab (hazard ratio [HR] = 1.84, 95% confidence interval [CI] =1.21–2.80) or trastuzumab without anthracyclines (HR = 2.53, 95% CI = 1.33–4.81) had increased risk of heart failure/cardiomyopathy vs controls, with highest risk observed in cases who received both anthracyclines and trastuzumab (HR = 3.68, 95% CI = 1.79–7.59). Increased risk of heart failure/cardiomyopathy was also observed in women who received any radiation therapy (HR = 1.38, 95% CI = 1.13–1.69) and aromatase inhibitors (HR = 1.31, 95% CI = 1.07–1.60).
Significantly increased risks of cardiovascular disease events according to treatments received included increased risk of:
- Stroke with aromatase inhibitor use (HR = 1.29, 95% CI = 1.07–1.55)
- Arrhythmia with aromatase inhibitor use (HR = 1.26, 95% CI = 1.06–1.51), anthracyclines without trastuzumab (HR = 1.54, 95% CI = 1.08–2.20), and anthracyclines with trastuzumab (HR = 2.57, 95% CI = 1.30–5.07)
- Cardiac arrest for left-sided radiation (HR = 1.91, 95% CI = 1.08–3.40), any radiation (HR = 1.59, 95% CI = 1.02–2.46), and aromatase inhibitor use (HR = 1.58, 95% CI = 1.04-2.42)
- Venous thromboembolic disease for left-sided radiation (HR = 1.61, 95% CI = 1.09–2.37) and any radiation (HR = 1.41, 95% CI = 1.07–1.86).
Significantly increased risk of cardiovascular disease–related death was associated with anthracyclines without trastuzumab (HR = 2.91, 95% CI = 1.96–4.33); trastuzumab without anthracyclines (HR = 2.00, 95% CI = 1.07–3.74); cyclophosphamide, fluoropyrimidine, and/or taxane treatment (HR = 2.87, 95% CI = 1.82–4.51); left-sided radiation (HR = 1.52, 95% CI = 1.16–1.98); any radiation (HR = 1.49, 95% CI = 1.21–1.79); aromatase inhibitor use (HR = 1.43, 95% CI = 1.18–1.73); and tamoxifen use (HR = 1.80, 95% CI = 1.15–2.82).
Significantly increased risk of all-cause mortality was associated with anthracyclines without trastuzumab (HR = 2.09, 95% CI = 1.78–2.45); trastuzumab without anthracyclines (HR = 1.77, 95% CI =1.32–2.36); cyclophosphamide, fluoropyrimidine, and/or taxane treatment (HR = 2.09, 95% CI = 1.70–2.57); any radiation (HR = 1.14, 95% CI = 1.04–1.25); and aromatase inhibitor use (HR = 1.29, 95% CI = 1.17–1.41).
The investigators concluded, “Women with breast cancer had increased incidence of cardiovascular disease events, cardiovascular disease–related mortality, and all-cause mortality compared with women without breast cancer, and risks varied according to the history of cancer treatment received. Studies are needed to determine how women who received breast cancer treatment should be cared for to improve cardiovascular outcomes.”
Dr. Greenlee, of Fred Hutchinson Cancer Research Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by grants from the National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.
