Long-term Safety of Radiotherapy and Breast Cancer Laterality in Older Survivors

Background: Although adjuvant radiotherapy (RT) following surgery for breast cancer improves overall survival, controversy exists about its long-term adverse impact on cardiovascular health in older survivors. Aim: To determine whether incident cardiovascular disease (CVD) is associated with RT and whether tumor laterality modifies this association. Methods: Women aged 65+ years diagnosed with stage I and II breast cancer between 1990 and 1994 were identified from three health plans. Women were followed through CVD outcomes, health plan disenrollment, death, or study end (December 31, 2004). The main independent variable was RT use. Adjusted HRs and 95% CIs were estimated using Cox proportional hazards models with time-dependent tamoxifen and RT use status. We adjusted for age, race, stage, estrogen receptor/progesterone receptor, hypertension, and diabetes. Results: In the full cohort (N = 806), RT was not associated with greater risk of CVD (maximum follow-up was 14 years). However, within the RT-exposed group (N = 340), women treated for left-side breast cancer had a significant increased risk of CVD outcomes (HR = 1.53, 95% CI: 1.06-2.21) compared with women with right-sided tumors. Conclusion: Laterality is critical to understanding the effect of RT on CVD. Studies of more contemporary cohorts of women treated with RT should incorporate this variable to determine whether the risk persists with refinements in the dosing and delivery of RT. Impact: As some irradiation to the heart is unavoidable even with refined modern RT techniques, continued effort is required to minimize such exposures, especially in older women with left-sided tumors. Cancer Epidemiol Biomarkers Prev; 20(10); 2120-6. (C)2011 AACR.