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.