Ionizing Radiation

Ionizing radiation to the chest in moderate to high doses (e.g., 1 to 3 Gy) at a young age substantially increases breast cancer risk. Among survivors of the atomic bombing of Hiroshima and Nagasaki, breast cancer risk was strongly associated with estimated breast tissue dose of radiation. Further, the relative risk of breast cancer associated with each radiation dose depended heavily on age at the time of the bombing; risk was highest for women exposed before age 10 years.

Studies of radiation therapy have revealed a similar pattern of excess risk of breast cancer associated both with higher doses and with younger ages at exposure. In a study of women who received substantial radiation to the chest as a result of repeated fluoroscopic examinations for tuberculosis, the maximum excess risk was among women with first exposure between the ages of 10 and 14 years, whereas women first exposed at age 35 years or older had virtually no excess risk.

In a study of women exposed to radiation therapy to the chest as treatment for Hodgkin's disease, the excess risk of breast cancer was similarly dependent on dose and age at irradiation. In a study of radiation treatment of breast cancer and development of second breast cancers, risk of second cases was significantly elevated (above its already high level) among women who underwent radiation at ages younger than 45 years.

In these studies, attained age and age at time of exposure were correlated. However, radiation exposure at a young age was associated with excess relative risk of early-onset breast cancer, and within categories of current age, the excess relative risks associated with early age of exposure are apparent.

These findings support the notion of age-dependent susceptibility to breast carcinogenesis and the hypothesis that undifferentiated breast cells are more vulnerable to cancer initiation than differentiated cells.

The risk associated with low-dose radiation exposure to the chest has been difficult to quantify, because the expected excess of breast cancers is small relative to the background risk.

Thus, the risk of breast cancer associated with low-dose radiation as in mammography has been estimated by extrapolating the dose-response relationship from studies of women exposed to higher doses of radiation. In this way, fewer than 1% of all cases of breast cancer have been estimated to result from diagnostic radiography.

Walter C. Willett, Beverly Rockhill, Susan E. Hankinson, David J. Hunter and Graham A. Colditz

W. C. Willett: Harvard Medical School, Boston, Massachusetts; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts
B. Rockhill: Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts
S. E. Hankinson: Departments of Medicine and Epidemiology, Harvard Medical School and Harvard School of Public Health, Boston Massachusetts