Elevated basal cortisol levels and attenuated ACTH and cortisol responses to a behavioral challenge in women with metastatic breast cancer

Hormones of the hypothalamic-pituitary-adrenal system were studied in 31 patients with early stage breast cancer and patients with metastatic breast cancer. Both groups received tamoxifen as first-line treatment. As a control group 15 age-matched healthy women participated in the study. The results showed that. breast cancer patients had significant elevations in basal cortisol levels compared to controls. Metastatic breast cancer patients had higher cortisol levels than early stage breast cancer patients. No significant differences between breast cancer patients and controls were found in basal plasma ACTH and prolactin levels. These data provide evidence that breast cancer is associated with a hyperactive adrenal gland, which may be due to the physiological stress associated with the presence of (micro)metastases or tumor cells in the circulation, in combination with administration of tamoxifen. In response to a behavioral challenge increases were observed in plasma ACTH and prolactin. Metastatic breast cancer patients had a faster prolactin response to acute stress than healthy women. However, metastatic breast cancer patients showed a blunted ACTH response compared to healthy women. Stress-induced ACTH responses and basal cortisol levels were negatively correlated in the metastatic group only. Thus, the blunted ACTH response to the behavioral challenge might be related to hypercortisolemia suggesting that the pituitary corticotroph cell in metastatic cancer is appropriately restrained possibly by the negative feedback effects of chronic cortisol elevations. Interestingly, the behavioral challenge induced decreases in cortisol levels in all three groups. However, metastatic breast cancer patients had a faster cortisol decline compared to healthy women. We hypothesize that this is caused by increased metabolic clearance of cortisol due to increased utilization of metabolic substrates often observed in the presence of a tumor. Copyright (C) 1996 Elsevier Science Ltd.