LONG-TERM CARDIAC MORBIDITY AND MORTALITY IN A RANDOMIZED TRIAL OF PREOPERATIVE AND POSTOPERATIVE RADIATION-THERAPY VERSUS SURGERY ALONE INPRIMARY BREAST-CANCER

Background and purpose: Some types of radiation therapy have been asso ciated with an increased risk of cardiac mortality and morbidity in pa tients with early-stage breast cancer. A relationship has been observe d between cardiac radiation dose-volume and the level of excess risk o f cardiac mortality. However, relatively few data are available on the morbidity from myocardial infarction associated with adjuvant radioth erapy. Patients and methods: From 1971 to 1976, a total of 960 patient s with operable breast cancer were randomly allocated to preoperative radiation therapy, postoperative radiation therapy or to surgery alone . A previous analysis of the cardiac dose-volumes with the treatment t echniques used in the trial indicated that the irradiated patients cou ld roughly be divided into three groups. Information on the number of myocardial infarctions was obtained through computerized record linkag e with a population-based registry of myocardial infarctions in Stockh olm County. Information on cause-specific mortality was obtained from the Swedish Cause-of-Death Registry. The median followup was 20 years (range 17-23 years). Results: A total of 58 patients developed an acut e myocardial infarction during the period of follow-up. The number of myocardial infarction cases was not significantly different between th e three treatment groups. When analyzed according to estimated cardiac radiation dose-volumes, patients in the highest dose-volume subgroup exhibited a hazard of myocardial infarction of 1.3 (95% CI 0.7-2.6) re lative to that of the surgical controls, whereas the corresponding rel ative hazard for the intermediate and low dose-volume subgroups was be low unity. Data on death due to cardiovascular disease showed that pat ients in the high dose-volume group exhibited a hazard of 2.0 (95% CI 1.0-3.9, P = 0.04) relative to that of the surgical controls. Concerni ng death due to ischemic heart disease, the relative hazard for the sa me subgroup was 2.5 (95% CI 1.1-5.7, P = 0.03). The difference between the groups was established after 4-5 years. The cumulative incidence curves continued to diverge up to about 10-12 years. No further diverg ence appeared after 12 years, but the number of events was low.Conclus ions: This analysis confirms and extends previous results from the tri al. Cardiac mortality was positively correlated with the cardiac dose- volume. Patients receiving high dose-volumes exhibited an increased mo rtality of ischemic heart disease, but not of myocardial infarction, w hich implies another mechanism, e.g. radiation-induced microvascular d amage to the heart. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.