"The hypothesis that diminished function of the pineal gland may promote the development of breast cancer in human beings is suggested by the relation between breast cancer and prolonged œstrogen excess, and by the observation that the pineal secretion, melatonin, inhibits ovarian œstrogen production, pituitary gonadotrophin production, and sexual development and maturation. The hypothesis is supported by the following points. (1) Pineal calcification is commonest in countries with high rates of breast cancer and lowest in areas with a low incidence; the incidences of pineal calcification and of breast cancer are moderate among the black population in the United States. (2) Chlorpromazine raises serum-melatonin; there are reports that psychiatric patients taking chlorpromazine have a lower incidence of breast cancer. (3) Although information is lacking on breast cancer, the pineal and melatonin may influence tumour induction and growth in experimental animals. (4) The demonstration of a melatonin receptor in human ovary suggests a direct influence of this hormone on the ovarian function, and possibly œstrogen production. (5) Impaired pineal secretion is believed to be an important factor triggering puberty (early menarche is a risk factor for breast cancer)."