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cardiotoxicity, breast cancer, chemotherapy, incidence, risk factors


Background: Anthracycline and trastuzumab are common breast cancer treatments. While improving survival, they elevate risk of congestive heart failure. The incidence of cardiotoxicity (CTx) with these therapies varies in the literature from 10% to 59%, higher than those reported in clinical trials (4%–10%) that excluded patients with preexisting cardiovascular comorbidities. Studies have failed to establish consensus on the risk factors for CTx associated with these therapies.

Purpose: We aim to determine the incidence and risk factors of CTx in breast cancer patients treated with anthracycline and/or trastuzumab at Aurora Health Care.

Methods: A retrospective review of patients with breast cancer who received anthracycline and/or trastuzumab from 2002 to 2011 yielded a total of 2,383 patients. Patients with a left ventricular ejection fraction (LVEF) recorded prior to treatment and at least one follow-up LVEF were included in analysis (n = 319, 13.4% of total cohort). Database queries and electronic medical records review (assisted by an in-house natural language processing tool) retrieved data on demographics, comorbidities, congestive heart failure symptoms, oncological treatments and LVEF. The study outcome was CTx, defined as a ≥ 10% decrease in LVEF to a level of < 55%. Chi-squared and Fisher’s exact tests were used for categorical variables to test differences in patient characteristics by CTx status (yes/no). Multivariate logistic regression analyses examined the association between risk factors and CTx.

Results: Average age of the patients was 54.9 ± 12.1 years; the cohort was comprised of 50.5% with obesity, 44.2% with smoking history and 47.3% with hypertension. A total of 79 patients developed CTx, an incidence of 24.8%. Multivariable analysis identified divorced/widowed marital status (odds ratio [OR]: 2.70, 95% confidence interval [CI]: 1.26–5.77), history of structural/electrophysiological (EP) cardiac disease (OR: 2.66, 95% CI: 1.24–5.70) and combined anthracycline-trastuzumab therapy (OR: 2.92, 95% CI: 1.48–5.77) as significant risk factors for CTx.

Conclusion: The incidence of CTx was greater in a community setting for which cardiac history and comorbidities are more diverse than in clinical trials. Consistent with prior literature, our study identified combined treatment with anthracycline and trastuzumab as a risk factor for CTx. Our study also suggests divorced/widowed marital status and prior structural/EP cardiac disease as additional risk factors for CTx. Further prospective studies are warranted for verification. We advocate for pre- and posttreatment cardiac monitoring of patients receiving these two therapies.