Affiliations of authors: A. K. Mohan, M. Hauptmann, M. S. Linet, E. Ron, J. H. Lubin, D. M. Freedman, M. M. Doody, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD; B. H. Alexander, Division of Environmental and Occupational Health, University of Minnesota, Minneapolis; J. D. Boice Jr., International Epidemiology Institute, Rockville, MD, and Department of Medicine, Vanderbilt University Medical Center, Nashville, TN; G. M. Matanoski, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
Correspondence to present address: Aparna K. Mohan, M.D., Ph.D., Office of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, Suite 200S, Bethesda, MD 20852 (e-mail: mohan{at}cber.fda.gov).
Reprint requests to: Dr. Michael Hauptmann, National Cancer Institute, Biostatistics Branch, 6120 Executive Blvd., Bethesda, MD 208927244 (e-mail: hauptmann{at}nih.gov).
ABSTRACT
We evaluated breast cancer mortality through 1997 among 69 525 female radiologic technologists who were certified in the United States from 1926 through 1982 and who responded to our questionnaire. Risk of breast cancer mortality was examined according to work history and practices and was adjusted for known risk factors. Breast cancer mortality risk was highest among women who were first employed as radiologic technologists prior to 1940 (relative risk [RR] = 2.92, 95% confidence interval [CI] = 1.22 to 7.00) compared with risk of those first employed in 1960 or later and declined with more recent calendar year of first employment (P for trend = .002). Breast cancer mortality risk increased with increasing number of years of employment as a technologist prior to 1950 (P for trend = .018). However, risk was not associated with the total number of years a woman worked as a technologist. Technologists who first performed fluoroscopy (RR = 1.69, 95% CI = 1.02 to 3.11) and multifilm procedures (RR = 1.87, 95% CI = 1.04 to 3.34) before 1950 had statistically significantly elevated risks compared with technologists who first performed these procedures in 1960 or later. The high risks of breast cancer mortality for women exposed to occupational radiation prior to 1950 and the subsequent decline in risk are consistent with the dramatic reduction in recommended radiation exposure limits over time.
Technologists were eligible for this study if they were certified by the American Registry of Radiologic Technologists (ARRT) for at least 2 years from 1926 through 1982 (15,16). Of the 106 884 female technologists who met the eligibility requirements, approximately 17 000 who were inactive registrants as of 1982 were traced using state and national databases (16). Current addresses were available for active registrants through annual recertifications with the ARRT. Deaths were identified through linkage with Social Security mortality files or the National Death Index; causes of death were obtained from death certificates or from the National Death Index Plus and were coded according to the International Classification of Diseases (17). A self-administered questionnaire was sent to the 99 234 female technologists who were known to be living and for whom a current address was available to ascertain their lifetime work histories, reproductive and family cancer histories, and other lifestyle factors (16). There were 69 525 respondents to the questionnaire. General characteristics and mortality rates were similar among respondents and nonrespondents (16). This study was approved by the Institutional Review Boards of the National Cancer Institute and the University of Minnesota.
Person-years of follow-up were compiled from the date of questionnaire completion to the date of death, last known vital status, or January 1, 1998, whichever occurred first. A total of 860 022 person-years were accumulated. Poisson regression (18) was used to estimate the relative risk (RR) of breast cancer mortality in relation to work history while adjusting for other covariates in the regression model. Analyses were stratified by attained age (a time-dependent variable representing age at each calendar year during the followup period) in 5-year age groups, calendar year of follow-up in 5-year categories, and race. Risks were calculated for the total number of years each subject worked as a radiologic technologist and the number of years each subject worked in the following calendar periodsbefore 1950, 1950 through 1959, 1960 through 1969, and 1970 and laterto reflect potential secular changes in recommended exposure limits (19,20). All statistical tests were two-sided, and P values for tests of trend were calculated based on the estimated slope of the corresponding continuous variable (18).
Among the women included in this study, 75% were born between 1940 and 1959, 76% were first certified by ARRT between 1960 and 1979, and 91% were less than 30 years old at certification. The average age at questionnaire completion was 38 years and the average length of follow-up was 12 years. Breast cancer risk was higher (RR = 1.28, 95% confidence interval [CI] = 0.86 to 1.89) among women who were 45 years old or older at menopause than it was among women who were younger than 45 years at menopause, and higher among those who reported having any relative with breast cancer than among those without such a family history (RR = 1.31, 95% CI = 1.00 to 1.72). The risk of breast cancer increased with a woman's increasing age when she gave birth to her first child (RR = 1.28, 95% CI = 0.92 to 1.78 for first births at ages 25 to 29 years and RR = 1.40, 95% CI = 0.92 to 2.14 for first births at age 30 years old or older, compared with women whose first births were at ages younger than 25 years) but was not associated with her age at menarche, the number of live births she had, or the number of mammograms she had received.
The risk of dying from breast cancer was statistically significantly higher for technologists who were first employed prior to 1940 (RR = 2.92, 95% CI = 1.22 to 7.00; P = .016) and for those who were first employed between 1940 and 1949 (RR = 2.44, 95% CI = 1.26 to 4.75; P = .008) compared with those first employed in 1960 or later (Table 1). Risk of death from breast cancer increased statistically significantly (P for trend = .002) with decreasing calendar year period that technologists first worked (Table 1
). The duration of employment as a radiologic technologist was not associated with breast cancer mortality in all time periods combined. Nevertheless, breast cancer mortality increased with an increasing number of years worked prior to 1950 (P for trend = .018) (Table 1
). The lower breast cancer mortality risk associated with working in more recent calendar periods may have been due to the effects of adjuvant therapy. However, we could not control for adjuvant therapy effects, because we did not collect data on the use of this form of treatment for breast cancer.
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This cohort of radiologic technologists is one of the few radiation worker cohorts that contain a substantial number of women (2123) for whom individual information on lifetime work history and cancer risk factors is available. A previous study among 5400 female Chinese medical x-ray workers who were exposed to occupational radiation between 1950 and 1985 found a 50% increase in breast cancer risk compared with hospital workers who were not exposed to radiation; those exposed before 1960 had a 70% increased risk (21). Estimated occupational radiation exposures are likely to have been higher among the Chinese medical radiation workers than among American medical radiation workers during the same time periods (13). Risk for breast cancer incidence was elevated, though it was not statistically significantly higher, among 3404 female Danish medical radiation workers employed from 1954 to 1982 compared with risk among Danish women in the general population (22). However, risk was not higher among 101 164 women (35% of whom were medical workers) in the Canadian national radiation worker registry who were monitored from 1951 through 1983 than it was among Canadian women in the general population (23).
Our study included a long follow-up period, a wide range of work practices, and sufficiently large numbers of technologists, which enabled us to make internal comparisons and thus minimize potential biases due to the healthy worker effect. It is difficult, however, to disentangle the effects of other variables (e.g., year of birth, attained age, and the calendar year of follow-up) that might also affect risk estimates. We performed a similar analysis using breast cancer mortality rates from the U.S. general population to estimate the background risks and found that, although the patterns of risk were similar to those we report here, the risk estimates themselves were somewhat smaller. Our findingthat breast cancer mortality was highest among technologists who first worked in the earliest calendar periodsprobably reflects changing exposures to radiation over time. Recommended exposure limits for medical radiation workers decreased from 70 rem/year before 1934 to 30 rem/year in 1934, 15 rem/year in 1949, and 5 rem/year in 1958 (24). This cohort, with its large number of women, estimated wide range of radiation doses received, and the extensive information available on risk factors, is uniquely suited to address the risks of breast and other cancers that are associated with long-term, low-dose radiation exposure.
NOTES
Supported in part by Public Health Service contracts NO1CP51016, NO2CP81121, and NO2CP81005 from the National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services.
We are grateful to Jerry Reid (American Registry of Radiologic Technologists) for continued support of this research project; Diane Kampa (University of Minnesota) for coordination of data collection; Kathy Chimes (Westat) for data management and vital status updates; and Roy Van Dusen, Joseph Barker, and Jeremy Bendler (Information Management Services, Inc.) for biomedical computing.
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Manuscript received December 17, 2001; revised March 26, 2002; accepted April 10, 2002.
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