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

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 ). In order to verify the role of organochlorines in increasing the level of estrogen receptors in breast tumors, the association between estrogen receptor levels and p,p′-DDE concentrations in breast adipose tissues of 18 patients enrolled in our previous case-control study ( 4 ) was tested by use of the Spearman rank correlation coefficient (twosided). Since p,p′-DDE is a stable DDT metabolite that accumulates in the body, its level probably reflects exposure to DDT over several decades. The Spearman rank correlation coefficient was adjusted on tumor size and patient age, because both may modulate tumor hormonal status and accumulation of p,p′-DDE. Correlation between estrogen receptor concentrations in breast tumors and concentrations of p,p′-DDE (i.e., dichlorophenyl dichloroethylene) in breast adipose tissues of 18 cancer patients As shown in Fig. 1 , estrogen receptor concentrations in breast tumor (mean = 23 fmol/mg of cytosol proteins) were associated with p,p′-DDE concentrations (mean = 1400 mg/kg lipids). The crude correlation coefficient was .55 ( P <.02) and was not significantly modified ( r = .52; P <.05) after adjustment for patient age (mean = 54 years) and tumor size (mean = 2.7 cm). The exclusion of two extreme values (one for DDE and one for estrogen receptor level) did not significantly modify the association. This finding suggests that the increase in estrogen receptor level in breast tumors observed during the past two decades could be explained in part by organochlorine exposure. If this hypothesis is confirmed, further limitations on production and usage of these chemicals will need to be implemented worldwide. Furthermore, because the maximum level of human exposure for organochlorines occurred during the late 1970s and given the relatively long latency of breast cancer (10-20 years), we should expect a decrease in breast cancer incidence in the forthcoming years in North America.