Anthracycline Cardiotoxicity: One Size Does Not Fit All!
Authors: D. L. Hershman, A. I. Neugut
Journal: JNCI Journal of the National Cancer Institute (2008)

The oncology community has known for more than 30 years that anthracycline-containing chemotherapy improves disease-free and overall survival in patients with breast cancer ( 1 ). Despite this, physicians are often reluctant to use it in certain “high-risk” groups, such as the elderly, due to concerns over the risk of short- and longterm cardiotoxicity. Although the risk of cardiotoxicity is dose dependent ( 2 , 3 ), it has been hard to predict which patients are at greatest risk for developing complications from treatment. Randomized clinical trials are excellent for establishing the effi cacy of new therapies by comparing experimental and standard therapies. However, many patients do not qualify for the rigorous entry criteria of most trials, and, thus, the effectiveness of these treatments, or how they work in the “real world,” often needs further clarifi cation, usually with the use of observational studies. Furthermore, determination of the long-term effects of treatments can be more of a challenge. Long-term toxic effects in particular are often rare, necessitating the evaluation of large numbers of patients with observation and follow-up for years following completion of primary treatment. To evaluate this prospectively would be prohibitively expensive. Patients who are enrolled in clinical trials are often healthier than those treated in the community, so risk estimates are often hard to generalize. Therefore, observational studies, using sophisticated epidemiological methods, are usually used to characterize risk and predictors of late effects in the community. A novel and popular recent approach has been to use large administrative databases to evaluate the long-term complications of treatment. One database that has been of particular value has been the Surveillance, Epidemiology, and End Results (SEER)– Medicare linked database, which contains clinical, demographic, and medical claims data on patients aged 65 years and older diagnosed with cancer since the early 1990s. The SEER – Medicare database is invaluable for studying unanticipated treatment effects and long-term outcomes in a population-based sample of patients who, for various reasons, have been underrepresented in clinical trials ( 4 ). Given the constraints on eligibility for clinical trials and other barriers to trial participation, analysis of such databases is the only way to fi nd out how treatments work in the real world. Using the SEER–Medicare database, the risk of congestive heart failure following anthracyclines has been characterized for women with early-stage breast cancer ( 5 , 6 ), and for patients with non-Hodgkin lymphoma ( 7 ). For each of these analyses, those with prior heart disease were less likely than others to receive anthracyclines, and known cardiac risk factors were associated with increased risk of congestive heart failure. Only hypertension was found to actually potentiate the risk of anthracycline-induced congestive heart failure ( 7 ). Although these studies were strengthened by large numbers of subjects and up to 10 years of follow