Excess risk of female breast cancer is among the most comprehensively documented late effects of exposure to substantial doses of ionizing radiation, based on studies of medically irradiated populations and the survivors of the atomic bombings of Hiroshima and Nagasaki, Japan. Relatively little is known about the joint effects of radiation dose with other breast cancer risk factors.

A case-control interview study of 201 living breast cancer cases and 580 matched controls, from a defined cohort of Japanese A-bomb survivors, was conducted to identify epidemiological variables strongly related to risk and to investigate their interactive relationship with radiation dose. A non-standard design was used, in which radiation dose was one of the matching variables; information about radiation dose effects was provided by a concurrent incidence study of the entire cohort.

Age at first full-term pregnancy, number of births, and total months of lactation were identified as strong, and partially independent, risk factors. Each of these variables interacted with radiation dose in a non-additive, and roughly multiplicative, relationship.

The above variables appeared to increase or decrease the excess breast cancer risk associated with radiation exposure in about the same ratios as they affected risk in nonexposed women. This finding is consistent with an initiation-promotion model in which promotion by factors related to reproductive history depends very little on how the cells were initiated.