Associations between adjuvant radiotherapy and different causes of death in a German breast cancer cohort

BACKGROUND: Studies of cohorts of breast cancer (BC) patients diagnosed before 1990 showed radiotherapy (RT) to be associated with increased cardiovascular (CVD) and lung cancer mortality many years after diagnosis. In the late 1990s, improvements in RT planning techniques reduced radiation doses to normal tissues. Recent studies did not consistently report higher RT-related mortality for CVD and second cancers. Aim of the study was to analyze specific causes of death after 3D-conformal RT in a recent BC cohort.

METHODS: Stage I-III BC patients diagnosed 2001-2005 and enrolled in the population based MARIEplus study were followed-up for 11.9 years (median). Associations between adjuvant RT and cause-specific mortality were analyzed by using competing risks models, yielding subdistribution hazard ratios (SHR) for RT directly related to cumulative incidences. Models were adjusted for differences in baseline characteristics applying inverse-probability-of-treatment-weighting (IPTW).

RESULTS: Of the 2951 patients, 2439 (83.0%) received RT. No significant association of RT with lung cancer mortality (SHRIPTW 0.88, 0.35-2.12), other cancer mortality (SHRIPTW 1.04, 95% CI 0.62-1.73) or cardiac mortality was observed (SHRIPTW 1.57, 0.75-3.29). Mortality from lung and other diseases were significantly lower in irradiated women (SHRIPTW 0.39, 95% CI 0.17-0.90 and SHRIPTW 0.58, 95% CI 0.34-0.97, respectively).

CONCLUSION: In line with recent studies, 3D-conformal RT did not significantly increase mortality from non-BC causes in the German MARIEplus cohort. Since long-term data are still sparse and event rates low in BC-cohorts, who received modern RT, investigation of possible late RT effects on mortality beyond 14 years of follow-up is warranted.