Local recurrence or cardiovascular disease: pay now or later.

© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: [email protected]. Radiation therapy is an essential component of the local management of breast cancer. The overview from the Early Breast Cancer Trialists’ Collaborative Group ( 1 ) indicates that adjuvant radiation therapy after breast-conserving surgery results in statistically significant reductions in the 5-year risk of local recurrence (26% versus 7%), the 15-year breast cancer mortality risk (5.4% reduction), and overall mortality (5.3% reduction). The benefits of radiation therapy are similar for those patients treated after mastec tomy, with reductions in local recurrence, breast cancer mortality, and overall mortality. Although the overview clearly shows the benefit of radiation, it also has confirmed the toxicities. Patients who were treated with radiation had increased risk of contralateral breast cancer, lung cancer, and mortality from cardiac disease (rate ratio = 1.27 , P <.001 ). The increase in non – breast cancer mortality among irradiated patients, particularly the increase in deaths from heart disease, diminished the benefit of radiation on overall survival endpoints. Individual randomized trials and epidemiologic studies have also demonstrated the cardiac toxicity of adjuvant breast radiotherapy ( 2 – 8 ). In a meta-analysis of eight randomized trials, Cuzick et al. ( 6 ) found a 62% increase in cardiac deaths among women who were treated with radiation therapy. However, all the individual studies in the meta-analysis were initiated before 1975 and used radiotherapy techniques that would now be considered suboptimal. Our own study ( 7 ), based on the Surveillance, Epidemiology, and End Results database, indicated that the risk of cardiac death due to radiotherapy has declined since the 1970s, but not enough time has elapsed to get fi rm estimates of the risk for women treated in the 1990s or 2000s, because cardiac toxicity is a late consequence of therapy that does not emerge until at least a decade after completing radiotherapy. The report by Hooning et al. ( 9 ) in this issue of the Journal provides important new information on the cardiac toxicity of radiation therapy. The study focused on a cohort of 4414 women who were at least 10-year survivors of breast cancer and were identifi ed through the Late Effects Breast Cancer Cohort in The Netherlands. The follow-up in this study was remarkably complete, with information available for 96% of all 10-year survivors. In addition, the median follow-up of almost 18 years was impressively long. Given the late emergence of radiation toxicity, the length of follow-up is critically important. The study has some other unique features: it evaluates morbidity as well as mortality, compares toxicity by radiation fi elds, and evaluates the impact of other cardiac risk factors. Several interesting fi ndings emerge from these analyses. First, this study is consistent with a growing body of literature showing that the risk of myocardial infarction due to radiation therapy has declined over time and provides additional good news for our patients ( 7 , 10 ). Thus, although patients who were diagnosed between 1970 and 1979 with radiation to the left chest wall or to right or left internal mammary fi elds had an increased risk of myocardial infarction, overall, the patients who were diagnosed Local Recurrence or Cardiovascular Disease: Pay Now or Later