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CHF in Older Women After Adjuvant Anthracycline-Based Chemotherapy for Breast Cancer

Adjuvant therapy that includes anthracyclines raises risk for adverse cardiac events.

Oncologists have known that cardiotoxicity can occur during anthracycline-based therapy ever since such therapy became an important component of cancer treatment nearly 3 decades ago. Particularly within the last 15 years, most patients who receive chemotherapy for early-stage breast cancer also receive an anthracycline (in the U.S., usually doxorubicin) as a component of the adjuvant chemotherapy regimen. In a past study, researchers reported asymptomatic cardiotoxicity (defined as a drop in left-ventricular ejection fraction of >10% to an LVEF of 55%) in 17% of patients who received 240 mg/m² of doxorubicin (cumulative dose; N Engl J Med 2005; 353:1673). In other studies, rates of clinical congestive heart failure (CHF) as high as 50% have been reported, depending on the cumulative anthracycline dose and the presence of other risk factors. As adjuvant chemotherapy has become more common overall (especially among older patients, whether or not they receive endocrine therapy), the pool of patients at risk for cardiotoxic reactions to anthracyclines has become larger. Older patients with comorbid conditions, such as hypertension, diabetes, and other cardiac problems, are at especially high risk. Previously, a group of investigators used the SEER (Surveillance, Epidemiology, and End Results) database to evaluate risk for cardiotoxicity in older women (age, 65) who received anthracycline-based chemotherapy therapy: The hazard ratio for cardiotoxicity was 2.48, and this heightened risk persisted for at least 5 years after therapy ended (J Clin Oncol 2005; 23:8597).

A new analysis of the SEER database adds to these concerns. More than 43,000 women (age range, 66–80) with no histories of CHF who were diagnosed with stage I to III breast cancer from 1992 through 2002 were evaluated. About 20% of women received adjuvant therapy; of those, half received anthracyclines. For 14,680 younger women (age range, 66–70), diagnoses of CHF within 10 years of therapy were made in 38.4%, 32.5%, and 29.0% of the anthracycline, nonanthracycline, and no-therapy groups, respectively. For 28,658 older women (age range, 71–80), no difference was noted in the rate of CHF among treatment groups, although the cumulative CHF incidence was higher in this age group as a whole (>50%) than in their younger counterparts.

After adjustment for therapy type, other independent predictors of CHF risk were identified. For each 10-year increment in age, risk for CHF doubled. Overall, CHF risk was 49% higher in black patients than in other patients. The number of women who had received trastuzumab was quite small, but higher risk for developing CHF was noted in trastuzumab recipients. Underlying coronary artery disease, diabetes, emphysema, hypertension, and peripheral vascular disease were all predictors of higher risk for subsequent CHF, whereas left-sided radiation therapy was not.

Comment: This study not only adds to the prior reports of high risk for CHF in older patients who receive anthracyclines but also raises the question of whether race influences the likelihood of this adverse event. As previous investigators have, these authors point out that black patients are more likely to receive anthracycline-based therapy because they more commonly have more-advanced disease at diagnosis and breast tumors that are hormone-receptor–negative. Additionally, the prevalence of and mortality related to CHF is greater in black patients than in white patients; this tendency might be exacerbated by the use of anthracycline-based chemotherapy in this population. The authors acknowledge the limitations of their observational study: lack of detail about cumulative doses of chemotherapy, doses of radiation therapy, and outcomes of treatments associated with development of CHF. Nevertheless, clinicians should be sensitive to adverse cardiac events that can occur in older women, and perhaps older black women in particular, who receive adjuvant anthracycline-based chemotherapy.

— William J. Gradishar, MD

Published in Journal Watch Oncology and Hematology October 30, 2007

Citation(s):

Pinder MC et al. Congestive heart failure in older women treated with adjuvant anthracycline chemotherapy for breast cancer. J Clin Oncol 2007 Sep 1; 25:3808.

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