Risk of cardiac death after adjuvant radiotherapy for breast cancer

J Natl Cancer Inst. 2005 Mar 16;97(6):419-24. doi: 10.1093/jnci/dji067.

Abstract

Background: Women with breast cancer who are treated with adjuvant radiation have a decreased risk of local recurrence but an increased risk of mortality from ischemic heart disease. Patients with left-sided breast tumors receive a higher dose of radiation to the heart than patients with right-sided tumors. Because radiation techniques have improved over time, we investigated whether the risk of death from ischemic heart disease after adjuvant breast radiotherapy decreased over time.

Methods: We used the 12-registry 1973-2000 dataset from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. Women (n = 27,283) treated with adjuvant radiation for breast cancer diagnosed in 1973-1989 were included in the study. Ischemic heart disease mortality was calculated at 15 years and compared for women diagnosed during 1973-1979, 1980-1984, and 1985-1989. Cox proportional hazards models were used to calculate the hazard of death from ischemic heart disease for women diagnosed 1973-1988 and censored at 12 years. All statistical tests were two-sided.

Results: There were no differences in age, race/ethnicity, disease stage, or follow-up time between the 13 998 women with left-sided and 13 285 with right-sided cancer. For women diagnosed in 1973-1979, there was a statistically significant difference in 15-year mortality from ischemic heart disease between patients with left-sided (13.1%, 95% confidence interval [CI] = 11.6 to 14.6) and those with right-sided (10.2%, 95% CI = 8.9 to 11.5) breast cancer (P = .02); no such difference was found for women diagnosed in 1980-1984 (9.4%, [95% CI = 8.1 to 10.6] versus 8.7% [95% CI = 7.4 to 10.0], respectively, P = .64) or 1985-1989 (5.8% [95% CI = 4.8 to 6.8] versus 5.2% [95% CI = 4.4 to 5.9], respectively, P = .98). In the Cox model, the hazard ratio [HR] for ischemic heart disease mortality for women with left-sided versus women with right-sided disease was 1.50 (95% CI = 1.19 to 1.87) in 1979. With each succeeding year after 1979, the hazard of death from ischemic heart disease for women with left-sided versus those with right-sided disease declined by 6% (HR = 0.94, 95% CI = 0.91 to 0.98).

Conclusions: Risk of death from ischemic heart disease associated with radiation for breast cancer has substantially decreased over time.

Publication types

  • Meta-Analysis
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / radiotherapy*
  • Confounding Factors, Epidemiologic
  • Death, Sudden, Cardiac / epidemiology*
  • Death, Sudden, Cardiac / etiology
  • Female
  • Humans
  • Myocardial Ischemia / etiology*
  • Myocardial Ischemia / mortality*
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / prevention & control*
  • Odds Ratio
  • Proportional Hazards Models
  • Radiotherapy, Adjuvant / adverse effects
  • Randomized Controlled Trials as Topic
  • Registries
  • Risk Assessment
  • SEER Program
  • Survival Analysis
  • Survival Rate
  • Time Factors
  • United States / epidemiology