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

## TL;DR

Radiotherapy increases the risk of a second breast cancer, but hormone therapy may reduce this risk in some patients.

## Contribution

The study reveals how radiotherapy and hormone therapy interact to influence contralateral breast cancer risk in survivors.

## Key findings

- Radiotherapy increases contralateral breast cancer risk, especially for ER+ cases in non-hormone therapy users.
- Hormone therapy appears to mitigate the increased risk of ER+ contralateral breast cancer caused by radiotherapy.
- Younger women exposed to radiotherapy face a higher risk of ER– contralateral breast cancer.

## Abstract

Radiotherapy increases contralateral breast cancer risk, while hormone therapy reduces it; their combined effects are unclear.

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.

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).

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.