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

TLDR

Adjuvant chemotherapy, especially anthracyclines, causes acute and chronic cardiotoxicity in breast cancer patients, and as long‑term survivors increase, mitigating these late effects becomes increasingly important. The study examined the cardiac effects of chemotherapy in older breast cancer patients (≥65 years) using a population‑based SEER‑Medicare cohort with long‑term follow‑up. The authors used SEER‑Medicare data, applied propensity‑score matching to adjust for baseline heart disease and other predictors, and fitted Cox proportional‑hazard models to estimate risks of cardiomyopathy, congestive heart failure, and heart disease in this population. Chemotherapy, particularly anthracycline doxorubicin, was associated with higher risks of cardiomyopathy (HR 2.48), congestive heart failure (HR 1.38), and heart disease (HR 1.35), with risks remaining elevated five years post‑diagnosis; patients receiving chemotherapy were younger, had fewer comorbidities, hormone‑receptor negative tumors, multiple primaries, advanced disease, and were less likely to have pre‑existing heart disease.

Abstract

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 > or = 65 years with long-term follow-up.In the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we analyzed treatments and outcomes among women > or = 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.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.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.