Occupation - Epidemiology and Nongenetic Causes of Breast Cancer

A review of 115 studies conducted between 1971 and 1994 found little support for an association between specific occupations and breast cancer risk. Limited evidencesuggested that cosmetologists, beauticians, and pharmaceutical manufacturing workers had a modestly elevated risk of breast cancer, but conclusions were not possible due to lack of adequate exposure data.

Although ionizing radiation is a recognized risk factor for breast cancer, none of the studies of radiation workers, including those of x-ray technicians and workers at uranium fuel plants and atomic energy plants, found an elevation of breast cancer risk among women in these occupations. The few studies carried out on specific occupational agents have not provided any evidence of association. In particular, although organic solvents may increase risk of various cancers in animals, women who worked in dry cleaning or shoe manufacturing, or who were exposed to trichloroethylene did not have an elevated risk of breast cancer.

Despite the large literature on occupation as a risk factor, most studies have simply examined associations between occupational title and breast cancer risk; specific information on exposure to potential carcinogens was collected in only a few studies.

Although some studies collected detailed information on lifetime occupational history, often broad occupational groupings representing only the most recent occupation were used in analyses. Furthermore, most studies have not controlled adequately for known breast cancer risk factors - reproductive factors, in particular - that are likely to confound any observed association with occupation. Employment outside the home, and in a specific occupation, is likely to be highly correlated with educational attainment and socioeconomic status, and thus with reproductive characteristics. In the few studies that have controlled for sociodemographic and reproductive risk, breast cancer risk was not found to vary across occupational groups.

In contrast, a consistent finding across studies that were unable to control for important confounding factors has been an increased breast cancer risk among more highly educated women, rather than a consistently observed association with any specific occupation. Thus, further analyses of occupational titles without consideration of known breast cancer risk factors or actual workplace exposures are unlikely to be informative.

Medical History
A variety of diseases and medications are known or suspected to cause or be associated with modifications of hormones or growth factors and thus may influence breast cancer risk. Type 2 diabetes mellitus has been suggested to increase risk of breast cancer. Hyperinsulinemia, as occurs in type 2 diabetes mellitus, may promote breast cancer, because insulin may be a growth factor for human breast cancer cells.

Furthermore, insulin levels are inversely related to levels of sex hormone-binding globulin, and thus are positively related to levels of available estrogens and androgens. Many studies have lacked information about the type and severity of diabetes, which makes the interpretation of the various findings difficult. In a case control investigation of subclinical diabetes, hyperinsulinemia with insulin resistance was a significant risk factor for breast cancer, independent of weight or body fat distribution.

Results of a case control study published in 1997 showed that a history of type 2 diabetes mellitus was associated with a 50% increase in postmenopausal breast cancer, again independent of weight. Further studies of the relationship between breast cancer and insulin resistance are warranted, because insulin resistance is modifiable through increases in physical activity, dietary changes, and maintenance of a lean body weight.

A relationship between thyroid disease and breast cancer has been suggested, but again, findings are inconsistent. Reports of a moderate increase in breast cancer risk after a diagnosis of thyroid cancer may reflect the effect of increased medical surveillance of thyroid cancer patients, as well as socioeconomic and reproductive risk factors that are shared by the two cancers. Most epidemiologic studies of prior diagnosis of thyroid disease have not found an association with breast cancer risk.

Strong evidence suggests that the use of nonsteroidal antiinflammatory drugs (NSAIDs), including aspirin, inhibits colon carcinogenesis in humans; this provides a rationale to investigate an inhibitory role of NSAIDs in breast carcinogenesis. Some epidemiologic studies have shown modest reductions in risk of breast cancer associated with NSAID use, whereas others have found none. Because most NSAID use is sporadic, it may be difficult to capture patterns of use on a questionnaire. Unanswered questions remain regarding the effect of regular NSAID use for long durations, the effect of different dosages, and the effects of different NSAIDs (in particular, aspirin versus nonaspirin).

A history of eclampsia, preeclampsia, or pregnancy-induced hypertension has been associated with a reduced risk of breast cancer in parous women in at least two case control studies. Explanations for these findings have focused on hormone-related factors: Women who develop preeclampsia have been found to have relatively low estrogen levels during pregnancy. However, nonspecific cellular immune responses may be involved as well.

An elevated risk of breast cancer associated with the use of antidepressants has been seen in at least one case control study, but this finding was based on a small number of participants. The literature on the effect of antidepressants on cancer in humans and in experimental animal models is conflicting, however. Future epidemiologic studies of this topic must control for possibly strong confounding factors, such as alcohol use, which may be associated with use of antidepressants. Furthermore, the indication for antidepressant use may itself be associated with increased cancer risk, and depression may possibly be an early symptom of occult cancer.

Cytotoxic drugs used in the treatment of cancer may exert their own carcinogenic effects. One category of cytotoxic drugs, alkylating agents, may lead to an increased risk of solid tumors, including breast cancer, although evidence for this hypothesis is weak.

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
D. J. Hunter: Departments of Epidemiology and Nutrition, Harvard School of Public Health, Boston, Massachussetts
G. A. Colditz: Department of Medicine, Harvard Medical School, Boston, Massachussetts


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