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site on endocrine disruption
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Fact SheetsBreast Cancer
Issue: Exposure to environmental chemicals is thought to play a causal role in the development of breast cancer and explain the alarming increase in the incidence of breast cancer.
Background: Although a number of genes such as BRCA1 and BRCA2 have been associated with breast cancer, they account for a small percentage of all of the cases of documented breast cancer. Therefore other factors such as gene environment interactions are thought to be involved in breast cancer initiation and promotion. Undiscovered breast cancer genes may also be important. Regardless, it has been proposed that exposures to environmental factors have a prominent role in the etiology of breast cancer.
Trends: The incidence rates of breast cancer have been shown to have increased since the 1940's. Increased rates during the 1980's were influenced by breast cancer screening programs. However a recent study suggests that the rates of breast cancer have leveled off since the early 1990s.
Consistency of the data: Data linking environmental exposures and breast cancer are equivocal. Several studies have reported an association between exposure to environmental contaminants that fall into the organochlorine class and include the DDT metabolite DDE. However other reports have failed to find a similar association. When all of the studies have been collected together and their data pooled for statistical re-analyses there was no association between organochlorine exposure and breast cancer. Reasons for failure to find an association between exposure to selected environmental contaminants and breast cancer are numerous and include but are not limited to the following: a) there is a long latency period between exposure and tumor formation; b) there are no definitive biomarkers for the onset or progression of breast cancer potentially resulting in misclassification of study subjects; and c) often exposure data are weak or absent. Additional difficulties in identifying biomarkers of breast cancer arise as most studies attempting to identify genes involved in breast cancer have focused on exposures during adulthood even though it has been suggested that exposures in utero or during the pubertal transition to estrogenic compounds may increase breast cancer risk perhaps via altered gene and/or protein expression in the fetus, neonate, or during the pubertal transition. Other factors that may contribute to failure to find an association, if one is indeed present is the influence of race and age. Some studies have shown a correlation between exposure and breast cancer diagnosis in one racial group but not in another. It may also be necessary to focus future studies on breast cancer estrogen-receptor status and menopausal status as the differences in hormonal status between pre- and post-menopausal women may preclude including them in the same analyses.
Experimental evidence: Numerous animal studies have been conducted to examine the effect of man-made chemicals on mammary tumor formation. These studies have demonstrated that environmental contaminants like DDE can promote tumor formation. However, rodent models of breast cancer have either used chemical inducers of tumor formation (DMBA or MNU) or transgenic mice bearing human breast cancer related genes linked with mouse viral promoters that are estrogen regulated. Unfortunately these models are highly artificial and thus limit translation of the findings from these studies to the human population.
Biological plausibility: Estrogen exposure is a well-documented risk factor for breast cancer. Hence it is reasoned that any additional estrogenic exposure increases a woman's risk for developing breast cancer. However, it must also be considered that the human exposure to environmental contaminants is very low. Moreover, the estrogenic activity of environmental contaminants is significantly lower than endogenous estrogen. Thus it is biologically plausible that estrogenic contaminants may exert tumor promoting activity in women the potential harm to health is complicated by the finding that consumption of foods containing dietary estrogens appears to reduce the risk of breast cancer. Thus it is possible that not all estrogens necessarily behave exactly the same way and therefore may have different biological consequences.
Conclusion: Taken together evidence of a trend, animal data and evidence of a biologically plausible mechanism suggests that there may be an association between exposure to environmental contaminants and breast cancer. However, there are many gaps in the knowledge set that need to be addressed in order to either substantiate or invalidate this association.
Key Papers on this issue:
