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J Am Heart Assoc. 2014 Feb 28;3(1):e000472. doi: 10.1161/JAHA.113.000472.

Risk prediction model for heart failure and cardiomyopathy after adjuvant trastuzumab therapy for breast cancer.

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Department of Internal Medicine, Section of General Internal Medicine, Yale School of Medicine, New Haven, CT.



Adjuvant trastuzumab improves survival for women with human epidermal growth factor receptor 2-positive breast cancer, but increases risk for heart failure (HF) and cardiomyopathy (CM). However, clinical trials may underestimate HF/CM risk because they enroll younger subjects with fewer cardiac risk factors. We sought to develop a clinical risk score that identifies older women with breast cancer who are at higher risk of HF or CM after trastuzumab.


Using the Surveillance, Epidemiology and End Results (SEER)-Medicare database, we identified women with breast cancer who received adjuvant trastuzumab. Using a split-sample design, we used a proportional hazards model to identify candidate predictors of HF/CM in a derivation cohort. A risk score was constructed using regression coefficients, and HF/CM rates were calculated in the validation cohort. The sample consisted of 1664 older women (mean age 73.6 years) with 3-year HF/CM rate of 19.1%. A risk score consisting of age, adjuvant chemotherapy, coronary artery disease, atrial fibrillation or flutter, diabetes mellitus, hypertension, and renal failure was able to classify HF/CM risk into low (0 to 3 points), medium (4 to 5 points), and high (≥6 points) risk strata with 3-year rates of 16.2%, 26.0%, and 39.5%, respectively.


A 7-factor risk score was able to stratify 3-year risk of HF/CM after trastuzumab between the lowest and highest risk groups by more than 2-fold in a Medicare population. These findings will inform future research aimed at further developing a clinical risk score for HF/CM for breast cancer patients of all ages.


breast cancer; cardiomyopathy; heart failure; trastuzumab

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