Risk of Heart Failure Among Breast Cancer Survivors

Abstract

Background: Cardiovascular disease (CVD) is prevalent among breast cancer survivors, leading to an increased risk of death in this patient population. Shared modifiable risk factors between CVD and cancer, such as obesity, physical inactivity, and diet, could offer a potential explanation for the increasing prevalence of CVD among cancer survivors. Another possible explanation is that frequently used breast cancer therapies, such as trastuzumab, are associated with cardiotoxicity, which could increase the risk of developing heart failure. Objective: The primary objective of this study was to assess if the age at breast cancer diagnosis was associated with the risk of heart failure across various age groups. Another objective of the study was to examine if the risk of heart failure among breast cancer survivors differed by chemotherapy use, specifically trastuzumab. Methods: A retrospective cohort analysis was conducted using 22,205 adult female breast cancer patients treated at the Northwestern Memorial Hospital. Patients were grouped into 50 years, 51-64 years, and 65 years for the age at breast cancer diagnosis. Kaplan-Meier curves for time to heart failure diagnoses were generated for the various age at diagnosis groups, and the Cox Proportional Hazards assumption was evaluated. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for important covariates concerning demographics, cancer characteristics, lab values, and comorbidities. Results: In assessing heart failure for all female breast cancer patients, older age at breast cancer diagnosis was associated with an increased risk of heart failure (HR 2.23, 95% CI 1.70-2.91 and HR 6.61, 95% CI 5.16-8.47 for 51-64 years and 65 years compared to 50 years, respectively). When adjusted for race, ethnicity, second cancer, smoking status, baseline cholesterol, baseline HDL, baseline glucose, coronary artery disease, and myocardial infarction, older age at breast cancer diagnosis remained associated with an increased risk of heart failure (HR 2.14, 95% CI 1.50-3.04 and HR 5.33, 95% CI 3.83-7.41 for 51-64 years and 65 years compared to 50 years, respectively). In assessing heart failure among female breast cancer patients treated with trastuzumab, age at breast cancer diagnosis was associated with an increased risk of heart failure only in the 65 years group (HR 1.90, 95% CI 0.84-4.29 and HR 3.29, 95% CI 1.43-7.58 for 51-64 years and 65 years compared to 50 years, respectively). When adjusted for race, ethnicity, and second cancer, age at breast cancer diagnosis was associated with an increased risk of heart failure in all age groups (HR 2.71, 95% CI 1.09-6.73 and HR 4.82, 95% CI 1.88-12.33 for 51-64 years and 65 years compared to 50 years, respectively) in female breast cancer patients treated with trastuzumab. Discussion: This analysis suggested a strong association between the age at breast cancer diagnosis and the risk of heart failure when examining all female breast cancer patients. Individuals diagnosed with breast cancer at an older age were at an increased risk of developing heart failure. However, this association varied when evaluating only female breast cancer patients treated with trastuzumab. This study provides important foundations to assessing the long-term impacts of breast cancer diagnosis and treatments, especially among younger adults compared to healthy peers. Thus, additional large-scale studies conducting a case-control analysis in this population and longitudinal studies in additional populations are required to fully elucidate the effect of age at breast cancer diagnosis on the risk of heart failure.

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