Breast cancer: critical data analysis concludes that estrogens are not the cause, however lifestyle changes can alter risk rapidly.

BACKGROUND: The theory that estrogens are causally associated with increased risk of breast cancer and the question of whether lifetime cumulative exposure is necessary are critically reviewed. METHODS: Systematic search was made of published epidemiological and clinical data relating to estrogen concentrations at different times and situations, and of breast cancer incidence with age and after lifestyle changes. RESULTS: Breast cancer incidence increases with age, although the rate of increase slows. Reproductive factors are known to affect risk, but data that do not fit the theory of estrogen causation include low estradiol levels and decline of estrogen excretion postmenopausally, rates in HRT-takers, absence of increased rate during or after pregnancy, and breast cancer in men. Breast cancer risk can be altered by external factors within a few years, as shown by studies in both Norway and England during World War II, by changing rates in migrant populations, and by the effect on rates of recent adiposity. CONCLUSIONS: It is probable that estrogens act as promoters rather than being directly causal. Even as promoters, lifetime exposure to estrogens is not necessary. The cause is most probably a lifestyle factor, changes in which can rapidly alter risk. This has important implications in the search for a causative factor.