Contralateral Breast Cancer After Radiotherapy and Hormone Therapy in Two Cohorts of Us Breast Cancer Survivors

Authors

Lene H S Veiga
Gretchen L Gierach
Susan A Smith
Rebecca M Howell
Matthew M Mille
Monjoy Saha
Rochelle E Curtis
Cody Ramin
Clara Bodelon
Heather Spencer Feigelson
Erin J Aiello Bowles
Diana S M Buist
Sheila Weinmann
Jacqueline B Vo
Choonsik Lee
Amy Berrington de Gonzalez

Language

English

Publication Date

1-1-2026

Journal

British Journal of Cancer

DOI

10.1038/s41416-025-03240-w

PMID

41238801

PMCID

PMC12819377

PubMedCentral® Posted Date

11-14-2025

PubMedCentral® Full Text Version

Post-print

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.

Keywords

Humans, Female, Breast Neoplasms, Middle Aged, Adult, Aged, Cancer Survivors, Aged, 80 and over, Retrospective Studies, United States, SEER Program, Neoplasms, Second Primary, Young Adult, Cohort Studies, Neoplasms, Radiation-Induced

Published Open-Access

yes

Recommended Citation

Veiga, Lene H S; Gierach, Gretchen L; Smith, Susan A; et al., "Contralateral Breast Cancer After Radiotherapy and Hormone Therapy in Two Cohorts of Us Breast Cancer Survivors" (2026). Faculty, Staff and Student Publications. 5862.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5862