Breast cancer incidence rates after radiation exposure in eight large cohorts are described and compared. The nature of the exposures varies appreciably, ranging from a single or a small number of high-dose-rate exposures (Japanese atomic bomb survivors, U.S. acute post-partum mastitis patients, Swedish benign breast disease patients, and U.S. infants with thymic enlargement) to highly fractionated high-dose-rate exposures (two U.S. tuberculosis cohorts) and protracted low-dose-rate exposure (two Swedish skin hemangioma cohorts). There were 1,502 breast cancers among 77,527 women (about 35,000 of whom were exposed) with 1.8 million woman-years of follow-up. The excess risk depends linearly on dose with a downturn at high doses. No simple unified summary model adequately describes the excess risks in all groups. Excess risks for the thymus, tuberculosis, and atomic bomb survivor cohorts have similar temporal patterns, depending on attained age for relative risk models and on both attained age and age at exposure for excess rate models. Excess rates were similar in these cohorts, whereas, related in part to the low breast cancer background rates for Japanese women, the excess relative risk per unit dose in the bomb survivors was four times that in the tuberculosis or thymus cohorts. Excess rates were higher for the mastitis and benign breast disease cohorts. The hemangioma cohorts showed lower excess risks suggesting ameliorating dose-rate effects for protracted low-dose-rate exposures. For comparable ages at exposure (approximately 0.5 years), the excess risk in the hemangioma cohorts was about one-seventh that in the thymus cohort, whose members received acute high-dose-rate exposures. The results support the linearity of the radiation dose response for breast cancer, highlight the importance of age and age at exposure on the risks, and suggest a similarity in risks for acute and fractionated high-dose-rate exposures with much smaller effects from low-dose-rate protracted exposures. There is also a suggestion that women with some benign breast conditions may be at elevated risk of radiation-associated breast cancer.

A case-control study to identify risk factors for epithelial ovarian cancer was undertaken among women in the age group 45-74 years who had been admitted to seven hospitals in Connecticut between July, 1977, and March, 1979. Characteristics that were found to increase the risk of epithelial ovarian cancer included being white, never having been pregnant, having a late age at menopause, having a family history of cancer of the ovary or endometrium, and having a long estimated number of years of ovulation. Prior use of post-menopausal estrogens did not alter the risk for epithelial ovarian cancer, but there was some indication that oral contraceptives protect against ovarian cancer. Women with ovarian cancer were somewhat more likely to have had a history of an underactive thyroid and were somewhat less likely to have had a history of an overactive thyroid than controls, although these trends were not statistically significant.

It is well established that exposure to ionizing radiation during or after puberty increases a woman's risk for breast cancer, but it is less clear whether exposure to ionizing radiation very early in life is also carcinogenic. We studied the incidence of breast cancer prospectively in a cohort of 1201 women who received x-ray treatment in infancy for an enlarged thymus gland and in their 2469 nonirradiated sisters. After an average of 36 years of follow-up, there were 22 breast cancers in the irradiated group and 12 among their sisters, yielding an adjusted rate ratio of 3.6 (95 percent confidence interval, 1.8 to 7.3). The estimated mean absorbed dose of radiation to the breast was 0.69 Gy. The first breast cancer was diagnosed 28 years after irradiation. The dose-response relation was linear (P less than 0.0001), with a relative risk of 3.48 for 1 Gy of radiation (95 percent confidence interval, 2.1 to 6.2) and an additive excess risk of 5.7 per 10(4) person-years per gray (95 percent confidence interval, 2.9 to 9.5). We conclude that exposure of the female breast to ionizing radiation in infancy increases the risk of breast cancer later in life.

Acute postpartum mastitis (APM) is an inflammatory-infectious condition of the breast, occurring commonly at childbirth or during lactation. A series of 601 women who received x-ray therapy for APM during the 1940's or 1950's have been followed up by mail questionnaire, with medical verification of pertinent conditions, to ascertain their incidences of breast cancer. Control subjects consisted of a series with APM who did not receive irradiation, plus the female siblings of both the APM groups, for a total of 1,239 controls. The groups have been followed up to 45 years; the average was 29 years. The relative risk (RR) for breast cancer, adjusted for age and interval since irradiation (or an equivalent entry definition for controls), was 3.2 for the irradiated breasts; the 90% confidence interval (CI) was 2.3-4.3. For a linear multiplicative model, the risk increased by 0.4% per rad (90% Cl of 0.2-0.7). The dose-response curve appeared to be essentially linear, except for a diminution of risk at high doses (greater than or equal to 700 rad). The fact that there were no treated breasts with doses between 0 and 60 rad, however, means that it was not possible to evaluate the curvature with the maximum contrast between low and high doses. The dose fractionation analyses showed that neither the number of dose fractions, the number of days between fractions, nor the dose per fraction had any apparent effect on breast cancer risk when the variables were analyzed separately. Similarly, when the fractionation variables were considered jointly in a Cox regression analysis, none was significant once total breast dose was controlled for. Analyses of age at irradiation did not show appreciable differences between age groups, although the numbers were too small to be clear-cut (only 64 women greater than 34 yr old at irradiation). Other studies have shown diminished risk associated with an older age at irradiation. The lack of diminished risk in this study may occur because during pregnancy and lactation the breasts are under increased proliferative stimulation by hormones, by comparison with the normal condition of breasts at older ages. An analysis of the temporal relationship of radiation to breast cancer showed that the RR did not vary systematically with interval since irradiation, but the absolute risk increased over time. This finding agrees with other studies that have also suggested a better fit for the multiplicative model.

A cohort of 2,657 infants in Rochester, New York, who were given x-ray treatment for a purported enlarged thymus gland, along with 4,833 siblings, have been followed by mail surveys through about 1986, which represents an average of 37 years of follow-up, to determine their incidence of thyroid cancer. Estimated thyroid doses ranged from 0.03 to > 10 Gy, with 62% receiving > 0.5 Gy. There were 37 pathologically diagnosed thyroid cancers in the irradiated group and five in the sibling controls. The dose-response relation was essentially linear, with no evidence of an additional dose-squared component. The estimated relative risk at 1 Gy was 10 (90% confidence interval 5-23). Thyroid cancer rates were elevated even at low doses; i.e., a dose-response analysis over the range of 0-0.3 Gy showed a significant positive slope. The risk ratio was declining over time but was still highly elevated to at least 45 years after irradiation. An examination of potential risk factors showed that older age at first childbirth was significantly associated with thyroid cancer risk. An evaluation of interactions between possible risk factors and radiation suggested that Jewish subjects and women with older ages at menarche or at first childbirth were at greater risk for radiogenic thyroid cancer.