Hormonal aspects in the causation of human breast cancer: epidemiological hypotheses reviewed, with special reference to nutritional status and first pregnancy.

Epidemiology of breast cancer has identified early age at menarche, late first pregnancy, low parity and late menopause as risk factors, but in addition genetic factors, height, weight and living in western countries play a significant role. The international variation in incidence is almost exclusively due to non-genetic factors. Hypotheses in prevention-oriented research are reviewed: 1. obesity-related oestrogen production as a stimulus of the tumour in postmenopausal women; 2. nutritional status and energy expenditure during puberty and adolescence, developed for fertility and fecundity and extended later to breast cancer; 3. reproductive life during early adulthood, age at first pregnancy and its specific effects on breast tissues. The message of preventability of breast cancer is that mammary epithelial differentiation should come early. Our insight concerning events in puberty and early adulthood can be consolidated in one concept on the risk of extended proliferation of breast epithelium during early adulthood in the absence of full differentiation induced by pregnancy. The combined effects of Western-type nutrition, lack of exercise and Western-type women's emancipation sets the stage for breast cancer already at a young age. Since it is unlikely that emancipated women in affluent societies will return to the original life-style of getting pregnant as soon as it is biologically possible, a novel daring way of protection has to be considered. Could a "Breast Differentiation Pill" be developed to offer protection?