Relations of plasma acth and cortisol levels with the distribution and function of peripheral blood cells in response to a behavioral challenge in breast cancer: An empirical exploration by means of statistical modeling

This study explores by means of statistical modeling the relations between adrenocorticotrophin hormone (ACTH) and Cortisol levels and distribution and function of peripheral blood cells in response to an acute stressor consisting of a standardized speech task in breast cancer patients with axillary lymphnode metastases and distant metastases. As a control group age-matched women participated in this study. The preliminary findings show that the effect of ACTH on imrrmnoreacrivity is related to the health of the donor. In node-positive breast cancer patients and healthy women, ACTH has a modest positive effect on T lymphocyte percentages and on pokeweedinduced proliferation at baseline and in response to the speech task. In contrast, in breast cancer patients with distant metastases ACTH has a negative effect on T lymphocyte percentages and function at baseline and in response to the stressor. Interestingly, neither ACTH nor Cortisol levels were related to natural killer (NK) cell percentages and natural killer cell activity (NKCA). In addition, it appeared that Cortisol had a positive effect on CD3 cell percentages when the health of the donor was taken into account. This effect was most distinct on CD3 cells measured at baseline. If replicated on a larger scale, these findings may indicate that the hypothalamic pituitary adrenal axis plays a role in the adaptation of the host defenses in reaction to acute stress, particularly those involving T lymphocytes. Moreover, these findings may suggest that the health of the donor may be an important effect modification factor in the relations between neuroendocrines and immunoreacttvity

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 taxoxifen. 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

Adjustment to breast cancer: The psychobiological effects of psychosocial interventions

This review focuses on the effects of psychosocial interventions on psychological and biological functioning of breast cancer patients. Once in their lifetime, one out of eleven women receive a diagnosis of breast cancer. A diagnosis of breast cancer is a severe stressful life event with profound consequences on all aspects of human life. Whether a woman will regain emotional balance and accept the idea of living with a potentially life threatening disease depends on her psychological resiliency. Provision of psychosocial interventions can improve these women's coping abilities and reduce emotional distress and feelings of isolation, and improve psychosexual functioning. Additionally, there exists some evidence that psychotherapy may prolong survival. Prolongation of survival may be related, in part, to an increase in certain aspects of immune function (e.g., natural killer cell activity). This is plausible because the function of the immune system seems to be related to mammary tumor growth. Therefore, future research should examine the degree to which the effects on mammary tumor growth relate to immune system changes

Effectiveness of a short-term group psychotherapy program on endocrine and immune function in breast cancer patients: An exploratory study

Cancer patients who had been treated for early stage breast cancer and were diagnosed with either positive axillary lymph nodes or distant metastases were randomly assigned to either a 13-week experiential-existential group psychotherapy (EEGP) program or a waiting list control (WLC) condition. Endocrine and immune measures were obtained before and after the intervention period. The findings of this study are that, after the 13 weeks of the experiment, patients in the EEGP group showed lower levels of plasma cortisol and lower levels of prolactin as well as lower percentages of natural killer cells, CD8 cells, and CD4 cells in addition to a lower proliferative response to pokeweed mitogen than patients in the WLC group. Importantly, this was only found in those breast cancer patients presenting relatively high endocrine and immune baseline levels, suggesting that the patients' profile with regard to endocrine and immune function at the start of a program can have an important effect. If replicated on a larger scale, the current results may be relevant for the treatment of breast cancer

Catechol-o-methyltransferase polymorphism and susceptibility to major depressive disorder modulates psychological stress response

Objectives The stress response is related to both physiological and psychological factors and is strongly marked by a neuroendocrine component. Genetic factors are believed to underlie individual differences in the degree of stress resilience and thereby contribute in determining susceptibility to stress-related pathologies like major depressive disorder (MDD). Little, however, is known about the genetic influence on the endocrine and behavioural stress response in relation to MDD. Methods Here, we sought to examine the effects of the catechol-o-methyltransferase polymorphism on psychological stress in three groups of individuals with different degrees of susceptibility to MDD (i.e. healthy controls, healthy high risk probands to MDD and those suffering from MDD). This genotype is involved in the metabolism of catecholamines (dopamine, norepinephrine and epinephrine). Results Allelic variations of this polymorphism were found to influence the degree of subjective stress experience and plasma epinephrine stress response. Interactions between catechol-o-methyltransferase polymorphism and diagnostic group in measures of plasma epinephrine, cortisol and subjective responses to psychological stress were also found, with the influence of the different alleles on these measures differing between healthy controls relative to MDD patients and high risk probands. Conclusion These observations support a possible role for catechol-o-methyltransferase polymorphism in the endocrine and subjective response to psychological stress and thus may qualify as a possible candidate gene involved in the pathogenesis of MDD