Could the Rising Levels of Estrogen Receptor in Breast Cancer Be Due to Estrogenic Pollutants?

Extract

The rising incidence of breast cancer during the last decades has been observed mainly among postmenopausal women and for estrogen-positive tumors. Moreover, it has been reported that, between 1973 and 1992, the median level of estrogen receptor in breast tumors increased steadily from 14 to 58 fmol/mg of protein ( 1 ). This increase was independent of tumor size, patient age, or changes in assay methods. Modifications in endogenous or exogenous hormonal factors may be involved in this rise, although their implication is still controversial.

Data ( 2 ) suggested that several environmental pollutants, in particular organochlorines such as DDT analogues and polychlorinated biphenyls (PCBs), exert estrogenic activity in both in vitro and in vivo models and, therefore, need to be considered as potential breast cancer risk factors.

Epidemiologic studies were conducted to assess the relationship between organochlorine exposure and breast cancer. Although three studies found a positive association, others obtained equivocal results [reviewed in ( 3 )]. In 1994, we reported that women with estrogen-positive tumors had a higher body burden of p,p′-DDE (dichlorodiphenyl dichloroethylene, the major DDT metabolite) than women with estrogen-negative tumors ( 4 ). It is interesting that organochlorines were later shown to increase the level of estrogen receptors in MCF-7 cells ( 5 ). Although the estrogenic potential of individual organochlorines is weak compared with that of estradiol, synergistic effects may result from combinations of compounds, as recently reported for the activation of the estrogen receptor in the yeast estrogen system ( 6 ).