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.
The incidence of neoplastic disease was determined by a mail survey of 2,872 young adults given X-ray treatments in infancy and of their 5,005 nonirradiated siblings. Newly diagnosed benign and malignant neoplasms appeared more frequently in the irradiated subjects than in their siblings or the age- and sex-matched general population of upstate New York. Only thyroid neoplasms occurred in sufficient numbers to permit statistical analysis for the effects on incidence of sex, age, and dose, and of being in a high-risk group (sub-group C). Thyroid cancers developed earlier in life than did benign neoplasms, especially in boys; benign goiters occurred after smaller doses, predominantly in females. Females had a greater risk of developing thyroid cancer than males--2,3 times for females of all ages and 5 times for young adults. Except for young adult females, there was no definite age effect. The risk of cancer (but not of benign goiter) was proportional to the thyroid dose, with a linear risk coefficient of 2.5/year/million people exposed to 1 rad for the entire irradiated population and 4.0 for subgroup C. The high risk of thyroid cancer in subgroup C may be the result of the high percentage of Jews, who had a 3.4-fold greater risk than non-Jews. Young adult Jewish females had a 17-fold increased risk. An incidental observation was an apparent increased incidence of asthma and rare diseases with abnormal immunologic features in the irradiated population.
NOMENCLATURE RR relative risk O/E observed to expected ratio z rate/ lo6 PY-rad standard deviate on the normal distribution excess tumors/106 personslyrlrad PY person-years at riskAbstract-In this paper thyroid tumor data from the 1971 survey of the Rochester, New York thymus irradiated population are further analyzed to study radiobiological and host factors. The analyses were based on the approx. 2650 irradiated subjects and 4800 sibling controls who had 5 or more years of follow-up. Twenty-four thyroid cancers and 52 thyroid adenomas were found in the irradiated group, and 0 thyroid cancers and 6 adenomas among the controls. The overall risk estimates were 3.8 thyroid cancers/ lo6 PY-rad and 4.5 thyroid adenomas/106 PY-rad. The dose-response data (thyroid dose range of 5 to > 1000rad) for thyroid cancer indicate both a linear and a dose-squared component, but no dose-squared component is evident for thyroid adenomas. At lower total doses ( <400 rad) there was a suggestion that dose fractionation diminished the thyroid cancer response, but a similar fractionation effect was not found for thyroid adenomas. The temporal pattern of tumors suggested an extended plateau of excess tumor production, rather than a "wavelike" temporal pattern. There was no evidence for an inverse relationship between thyroid radiation dose and thyroid cancer latency. Female and Jewish subjects had a higher risk of radiation-induced thyroid cancer than did their respective counterparts. The additive and multiplicative models of radiation effects were compared with respect to sex differences; neither model provided a superior fit to the data. The tentative nature of the conclusions is stressed because of the relatively small number of thyroid cancers.
Breast cancer has been studied by mail survey up to 34 years in 571 of 606 women treated with x-rays for acute postpartum mastitis. The incidence of neoplasms was compared with that of three nonirradiated control groups--nonirradiated sisters of the treated women, women with acute postpartum mastitis not treated with X-rays, and their nonirradiated sisters. For the irradiated group, with mean dose of 247 rads to both breasts, the overall relative risk of breast cancer was 2.2 for years 10-34 post irradiation and 3.6 for years 20-34. The dose response for malignant and benign breast neoplasms was compatible with a linear fit. For comparable total doses, fractionation of exposure did not reduce carcinogenic action. Women over age 30 years at radiation treatment had as great an excess risk of breast cancer as did younger women. The overall excess risk of developing breast cancer was about 8-10 cases per million women per rad per year, an increase of about 0.5% per rad.
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