Contralateral breast cancer after radiotherapy and hormone therapy in two US cohorts of breast cancer survivors

Radiotherapy increases contralateral breast cancer risk, while hormonal therapy reduces it; their combined effects are unclear. Analysis of data from two US retrospective cohort studies of 5-year breast cancer survivors (stage I-III, ages 20-84) evaluated these combined effects. The Kaiser Permanente cohort (KP; n=9053) included 353 contralateral breast cancer cases (73% ER+); the SEER cohort (n=244,834) included 10,470 cases (72% ER+). Among women with ER+ first breast cancer, radiotherapy increased the risk of ER+ contralateral breast cancer in non-users of hormone therapy (KP RR 2.2; 95% CI 1.20 to 4.14; SEER 1.12; 1.04 to 1.21), but not in users of hormone therapy (KP 0.88; 0.61 to 1.26; SEER 1.03; 0.94 to 1,12). In KP, higher radiation dose increased risk of ER+ contralateral breast cancer among non-users of hormone therapy (ERR/Gy 1.39; 95% CI 0.33 to 3.66) but not among users (- 0.13; -0.36 to 0,23). Radiotherapy also increased risk of ER- contralateral breast cancer (KP RR 1.85; 95% CI 0.95 to 3.59; SEER 1.12; 1.01-1.23), especially in younger exposed women (age <40 versus 40+ years SEER RR 1.31; 1.02-1.69). The authors conclude that radiotherapy increased contralateral breast cancer risk, but hormone therapy appeared to mitigate this risk for ER+ cases.