Cardiovascular outcomes in women with advanced breast cancer exposed to chemotherapy

PURPOSE: To quantify incidence of cardiovascular outcomes in patients with advanced breast cancer receiving cardiotoxic and non-cardiotoxic chemotherapy. METHODS: This study identified all women at a Midwestern health system with initial diagnosis of American Joint Commission on Cancer Stage III/IV breast cancer (1995-2003) and random sample of 50 women initially diagnosed with Stage I/II who progressed to Stage III/IV. The rate of new cardiovascular outcomes (heart failure, dysrhythmia, and ischemia events) for cardiotoxic (anthracycline or trastuzumab) and non-cardiotoxic agents was calculated. RESULTS: Of 315 patients, 90.5% (n = 285) received systemic cancer therapy; 67.7% (n = 193) received cardiotoxic drugs. Older patients were less likely to receive cardiotoxic agents (86.4%, ≤59 years vs. 31.9%, 70+ years). Adjusting for age, race, stage, surgery/radiation, estrogen receptor/progesterone receptor status, and diagnosis year, rate of new cardiac events was higher in patients exposed to cardiotoxic drugs compared with those exposed to non-cardiotoxic drugs (adjusted hazard ratio = 2.5, 95%CI = 0.9-7.2). Patients with cardiac event history (relative risk = 3.2, 95%CI = 2.0-5.1) and those with heart failure history (relative risk = 5.9, 95%CI = 2.4-14.6) were more likely to receive non-cardiotoxic treatment. Heart failure events occurred steadily over time; after 3 years of follow-up, 16% exposed to cardiotoxic drugs experienced an event, and 8% of those exposed to non-cardiotoxic drugs experienced an event. CONCLUSIONS: Patients with cardiac comorbidity are less likely to receive cardiotoxic agents. Use of cardiotoxic agents is common; treatment is related to patient and tumor characteristics and is associated with substantial risk of cardiotoxicity that persists during patients' remaining lifespan.