Timing of Menarche and First Birth in Relation to Risk of Breast Cancer in A-Bomb Survivors

Background: The length of the interval between age at menarche and age at first birth is positively associated with breast cancer risk. We examined the risk of breast cancer in atomic bomb survivors to investigate whether women exposed to radiation between menarche and first birth had a higher risk of radiogenic breast cancer than women exposed at the same age but outside this interval. Methods: Women (n = 30,113) were classified into three reproductive status at the time of the bombings (ATB) categories (premenarche, between menarche and first birth, or after first birth). Poisson regression was used to test the primary hypothesis. Results: When the background rate of breast cancer was taken to depend on city, age ATB, and attained age only, the radiation-related excess relative risk (ERR) varied significantly among the three categories (P = 0.049). However, after controlling for significant heterogeneity in the baseline risk of breast cancer between reproductive status ATB groups (P < 0.001), no significant heterogeneity (P = 0.88) was observed in the ERR, with an ERR per Gy of 1.36 [95% confidence interval (CI), 0.54-2.75] for women exposed between menarche and first birth ATB, and 1.07 (95% CI, 0.22-3.62) and 1.53 (95% CI, 0.63-2.90) for those exposed premenarche or after first birth, respectively. Conclusions: The radiation-associated risk of breast cancer does not vary significantly by reproductive status ATB. Impact: It is possible that radiation exerts similar carcinogenic effects on the breast regardless of its stage of differentiation, or that the differences in radiosensitivity are too small to be detected in this cohort. Cancer Epidemiol Biomarkers Prev; 19(7); 1746-54. (C) 2010 AACR.