Background – With a few exceptions, the number of new breast cancer cases among women is increasing in almost all Western countries. Although late age at first child birth and genetics are shown to contribute to the increase in breast cancer, the sheer number of newly diagnosed cases cannot solely be explained by these factors. Do environmental influences, including exposure to mixtures of chemicals, also play a role?
Hypothesis – Considering that natural estrogens and man-made estrogens used as pharmaceuticals contribute to breast cancer, concerns arise about the potential role of industrial chemicals and pesticides with hormonal activity. Such chemicals include several that have been banned already, but can still be found in human tissues, such as polychlorinated biphenyls (PCBs) and DDT. A large number of chemicals currently used in consumer products also fall in this category (bisphenol A, UV-filter substances and many more). The studies carried out to date to examine whether certain environmental chemicals are implicated in breast cancer leave much uncertainty about a possible link. But to avoid wrongly dismissing a role for chemicals in breast cancer, the issue of simultaneous exposure to scores of chemicals must be addressed. However, the majority of published epidemiological studies have focused on single chemicals. Methods of dealing with mixture exposure in epidemiology are poorly developed.
Methods/Work performed – The involvement of weakly estrogenic chemicals in breast cancer is often dismissed on two counts: First, it is widely held that their potency is insufficient to contribute significantly to the effects of endogenous steroidal estrogens. Second, it is seen as unlikely that chemicals present at low levels can act together to produce joint effects. Both these ideas were tested experimentally by conducting multi-component mixture studies with combinations of estrogenic chemicals in cell-based assays.
Results and conclusions – Experiments with in vitro estrogenicity assays (yeast estrogen screen, E-Screen) have shown that the combined effects of multi-component mixtures of xenostrogens could be predicted well from information about their individual potency. When the individual chemicals were combined at concentrations below the sensitivity limits of these assays, significant mixture effects were observed. The effects of steroidal estrogens could be exacerbated by co-exposure to low levels of weakly active estrogenic chemicals. These results show that a potential role of such chemicals in breast cancer cannot be dismissed solely on the basis of their low potency. If exposure is to sufficient numbers of weak xenoestrogens, at low levels, significant modulations of the effects of steroidal estrogens may occur. The implications of these findings for epidemiology and risk assessments will be discussed.