Depression of serum melatonin in patients with primary breast cancer is not due to an increased peripheral metabolism

Serum melatonin and its main metabolic product 6‐sulfatoxymelatonin were determined in 17 patients with breast cancer (BC) with either a fresh primary tumor (nine) or a secondary tumor (eight) as well as in four patients with untreated benign breast disease (controls). Circadian rhythms were detected in all groups with acrophases around 2 AM for melatonin and around 3 AM for 6‐sulfatoxymelatonin. The nocturnal melatonin and 6‐sulfatoxymelatonin concentrations were significantly depressed in the group of patients with primary breast cancer compared with controls (P < 0.01, P < 0.025). The circadian amplitudes of melatonin and 6‐sulfatoxymelatonin were also depressed by 81% (P < 0.01) and 63% (P < 0.01). In contrast, patients with secondary BC had nocturnal melatonin and 6‐sulfatoxymelatonin concentrations and amplitudes similar to controls. These results demonstrate that the depression of circulating melatonin in patients with primary BC is not due to an enhanced degradation to 6‐sulfatoxymelatonin in the liver but must be due to a reduced activity of the pineal gland.