Work

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

Year: 2025

Type: article

Abstract: BACKGROUND: Radiotherapy increases contralateral breast cancer risk, while hormone therapy reduces it; their combined effects are unclear. METHODS: Data from two US retrospective cohort studies of 5-year breast cancer survivors (stage I-III, ages 20-84), Kaiser Permanente (KP, 1990-2012) and SEER (1990-2013), were analysed. Contralateral breast radiation doses were estimated for the KP cohort. Multivariable Poisson regression estimated relative risks (RRs) and excess relative risks per Gray (ERR/Gy), stratified by hormone therapy use. RESULTS: KP cohort (n = 9053) included 353 contralateral breast cancer cases (73% ER+); 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:1.20-4.14; SEER RR = 1.12, 1.04-1.21), but not in users (KP RR = 0.88, 0.61-1.26; SEER RR = 1.03, 0.94-1.12). In KP, higher radiation dose increased risk of ER+ contralateral breast cancer among non-users (ERR/Gy=1.39, 95%CI:0.33,3.66), but not among users (ERR/Gy= -0.13, -0.36,0.23). Radiotherapy also increased risk of ER- contralateral breast cancer (KP RR = 1.85, 95%CI: 0.95-3.59; SEER RR = 1.12, 1.01-1.23), especially in younger exposed women (SEER RR = 1.31, 1.02-1.69 for age <40 vs 40+ years). Additionally, the risk increased linearly with radiation dose to the contralateral breast (ERR/Gy=0.87, 0.04,2.72). CONCLUSIONS: Radiotherapy increased contralateral breast cancer risk, but hormone therapy appeared to mitigate this risk for ER+ cases. These findings have important implications for individuals exposed to chest radiation.

Source: British Journal of Cancer

DOI: 10.1038/s41416-025-03240-w