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Chemotherapy and Cardiotoxicity in Older Breast Cancer Patients: A Population-Based Study

From the Department of Medicine and the Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, and Departments of Epidemiology and Biostatistics, Mailman School of Public Health, Columbia University; and New York Presbyterian Hospital, New York, NY

Address reprint requests to Dawn Hershman, MD, MS, Herbert Irving Comprehensive Cancer Center, 161 Ft Washington, Rm 1068, New York, NY 10032; e-mail: dlh23{at}columbia.edu

PURPOSE: Adjuvant chemotherapy, especially with anthracyclines, is known to cause acute and chronic cardiotoxicity in breast cancer patients. We studied the cardiac effects of chemotherapy in a population-based sample of breast cancer patients aged 65 years with long-term follow-up.

PATIENTS AND METHODS: In the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we analyzed treatments and outcomes among women 65 years of age who were diagnosed with stage I to III breast cancer from January 1, 1992 to December 31, 1999. Propensity scores were used to control for baseline heart disease (HD) and other known predictors of chemotherapy, and Cox proportional hazards models were used to estimate the risk of cardiomyopathy (CM), congestive heart failure (CHF), and HD after chemotherapy.

RESULTS: Of 31,748 women with stage I to III breast cancer, 5,575 (18%) received chemotherapy. Chemotherapy was associated with younger age, fewer comorbidities, hormone receptor negativity, multiple primary tumors, and advanced disease. Patients who received chemotherapy were less likely than other patients to have pre-existing HD (45% v 55%, respectively; P < .001). The hazard ratios for CM, CHF, and HD for patients treated with doxorubicin (DOX) compared with patients who received no chemotherapy were 2.48 (95% CI, 2.10 to 2.93), 1.38 (95% CI, 1.25 to 1.52), and 1.35 (95% CI, 1.26 to 1.44), respectively. The relative risk of cardiotoxicity among patients who received DOX compared with untreated patients remained elevated 5 years after diagnosis.

CONCLUSION: When baseline HD was taken into account, chemotherapy, especially with anthracyclines, was associated with a substantially increased risk of CM. As the number of long-term survivors grows, identifying and minimizing the late effects of treatment will become increasingly important.

Supported by an American Society of Clinical Oncology Career Development Award (D.L.H.), K07 Award No. CA95597 from the National Cancer Institute (D.L.H.), K05 Award No. CA89155 from the National Cancer Institute (A.I.N.), and Grant No. RSGT-01-024-04-CPHPS from the American Cancer Society (A.I.N.).

This study used the linked Surveillance, Epidemiology, and End Results-Medicare database. The interpretation and reporting of these data are the sole responsibility of the authors.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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