Breast cancer: Evidence for xeno-oestrogen involvement in altering its incidence and risk

Abstract

This review specifically addresses whether environmental oestrogen xenobiotics increase breast cancer risk, and thus contribute to the gradual and persistent rise in breast cancer incidence since 1940. Xeno-oestrogens are a structurally diverse group of chemicals that includes organochlorine pesticides, herbicides, pollutants, industrial chemicals, and metabolites of potent carcinogens. They possess oestrogenic activity, and when compared to that of 17β-oestradiol, their oestrogenic potency ranges from weak (10-3) to extremely weak (10-6), using a variety of in-vivo and in-vitro endpoints. It is evident that the sequestering of xeno-oestrogens in mammalian adipose tissue and their gradual release may not be a property of all xeno-oestrogens. Long-term animal carcinogenicity studies of individual xeno-oestrogens [e.g., dichlorodiphenyl trichloroethane (DDT), dichlorodiphenyl dichloroethane (DDE), dieldrin, aldrin, polychlorinated biphenyls (PCBs), phthalates] are revealing. Only atrazine has been shown to have the mammary gland as a marginal target site for cancer. A number of xeno-oestrogens (DDT, DDE, PCBs) induce lymphomas and tumours in the liver and lung, and in various murine species. Human neoplasms induced by individual xeno-oestrogens largely reflect those induced in animal studies, with possible additional associations of pancreatic and haematologic cancers. Earlier small case-control studies lent credence to an association of xeno-oestrogens and breast cancer. Subsequent larger prospective case-control studies from the USA, Europe, and Mexico, however, do not support this relationship. It is concluded from the evidence presented that xeno-oestrogens do not play a significant role in human breast cancer aetiology, its subsequent development, or in the gradual rise in breast cancer incidence.