Radiation-associated breast cancer and gonadal hormone exposure: a report from the Childhood Cancer Survivor Study

Background: The relationship between hormone exposure and breast cancer risk in women treated with chest radiotherapy for childhood cancer is uncertain. Methods: Participants included 1108 females from the Childhood Cancer Survivor Study who were diagnosed with childhood cancer 1970-1986, treated with chest radiotherapy, and survived to ages >= 20 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) from Cox models adjusted for chest radiation field, delivered dose, anthracycline exposure, and age at childhood cancer estimated risk. Results: Among 195 women diagnosed with breast cancer, 102 tumours were oestrogen-receptor positive (ER+). Breast cancer risk increased with >= 10 years of ovarian function after chest radiotherapy vs <10 years (HR = 2.89, CI 1.56-5.53) and for radiotherapy given within 1 year of menarche vs 41 year from menarche (HR = 1.80, CI 1.19-2.72). Risk decreased with decreasing age at menopause (P-trend = 0.014). Risk factors did not differ for ER+ breast cancer. Survivors with an age at menopause <20 years treated with hormone therapy had a lower breast cancer risk than premenopausal survivors (HR = 0.47, CI 0.23-0.94). Conclusions: Endogenous hormones are key contributors to breast cancer observed among childhood cancer survivors. Hormone therapy given for premature ovarian insufficiency does not fully replace the function that endogenous hormones have in breast cancer development.