DESCRIPTION (Applicant's Description) Few studies have investigated the long-term consequences of childhood irradiation of the female breast. Radiation exposure of the immature breast may act as a tumor initiator, increasing the susceptibility of the exposed cells to the tumor-promoting effects of a variety of subsequent exposures, including hormones, dietary factors, chemicals, or viruses. Epidemiologic studies of populations of women who were exposed to ionizing radiation (including postpartum mastitis patients, atomic bomb survivors, and patients treated for ankylosing spondylitis) have shown that breast tissue is susceptible to radiogenic cancer; however, the majority of the women in these studies were adults. It is now hypothesized that women exposed to ionizing radiation as infants or children are at even greater risk of developing breast cancer than women who were first exposed at older ages. A study of female tuberculosis patients who received multiple fluoroscopic examinations of the lungs reported that the greatest absolute excess risk of breast cancer occurred among women who were first exposed between 15 and 19 years of age, while no increased risk of breast cancer was observed among women who were over 30 years of age at the time of first exposure. Similarly, the atomic bomb survivor studies report that girls under 9 years of age at exposure were at greater risk than those who were 10-19 and that these girls were, in turn, at greater risk than those women who were 20-29 years of age at the time of the bombing. In this application, we propose to determine the feasibility of conducting a retrospective follow-up study to evaluate the hypothesis that irradiation of the immature breast tissue of prepubertal girls increases their risk of subsequent breast cancer. We have available to us the population of approximately 600 girls who received prophylactic irradiation for an "enlarged" thymus gland and who were diagnosed in infancy and early childhood at the Massachusetts Eye and Ear Infirmary from 1924 to 1946. The current age range of this population is 49 to 71, the years of peak breast cancer incidence. Only one other cohort of similar patients has been followed. These women, whose mean age was just 36, had an increased risk of breast cancer that was 3.6 times (95 percent CI 1.8-7.3) that of their non-irradiated sisters. With the reassembly and follow-up of the Massachusetts Eye and Ear population, we would have the opportunity to investigate the role that timing of exposure plays in determining the susceptibility of breast tissue to malignant transformation.