Perspectives of breast cancer etiology: synergistic interaction between smoking and exogenous hormone use.

To explore breast cancer etiology, literature was searched using Medline. We explored the 1) plausibility of smoking in breast carcinogenesis; 2) physiological properties, susceptibility windows, and exposure timing of breast cells; 3) role of exogenous hormones in breast carcinogenesis; 4) biological mechanism of synergistic interactions between smoking and exogenous hormones in breast carcinogenesis; and 5) evidence from epidemiologic studies and the fitted secular trend between smoking rate, exogenous hormone use, and breast cancer incidence in past decades. We deduced that exogenous hormone use per se is not a significant cause and its association with breast cancer is distorted by chronic exposure to environmental carcinogens, especially smoking.