Abstract
A possible role for the pineal and melatonin in malignant disease is suggested by the studies of hormone-dependent tumours presented here. The most dramatic observation of the effect of the pineal and melatonin in malignancy is that melatonin protects against, while pinealectomy enhances, 7,12-dimethylbenz[a]anthracene-induced mammary tumours in rats. Melatonin may protect against tumours through a suppressive effect on prolactin secretion or an action on oestrogen receptors. Melatonin can change the concentration of oestrogen receptors in hamsters, both juvenile and adults, and in a human breast cancer cell line. The long-term effect of melatonin in the ovariectomized adult hamster and in human reast cancer cells is to inhibit oestrogen-stimulated growth. A possible relationship between melatonin and oestrogen receptors was examined in women with breast cancer. An inverse correlation was observed between the oestrogen receptor concentration in each patient's tumour and her peak plasma melatonin level, suggesting that the more hormone dependent the breast cancer the more blunted the daily melatonin rhythm. Thus, the more robust the daily melatonin rhythm the greater the protective effect on hormone-dependent breast cancer. Unfortunately, this hypothesis is not easily tested as shown in a study of women at high risk for developing breast cancer. These women had daily melatonin profiles that did not differ from those of a normal population. Thus, the use of plasma melatonin as a screening tool for breast cancer risk is not reasonable; however the basic and clinical data argue that the role of melatonin in endocrine-related cancers requires more extensive clinical investigation.