Cancer Control Research
1R03CA077120-01
Janusek, Linda W.
STRESS AND IMMUNITY--IMPLICATIONS FOR BREAST CANCER
AbstractDESCRIPTION (Applicant's Description) Advances in psychoneuroimmunology have
provided clear and compelling evidence that stress leads to changes in
immune function. Stress-induced immune modulation may influence the outcome
and control of breast cancer. To understand the effect of stress on a
woman's immune system and its relationship to breast cancer control,
requires the evaluation of a naturalistic stress paradigm. Based on our
preliminary studies, the experience of diagnostic breast biopsy provides
such a stress paradigm. Our results show that the stress of impending
breast biopsy leads to psychological stress, neuroendocrine activation, and
a decrease in natural killer (NK) cell activity (NKCA). NK cells mediate
natural resistance against tumor cells, and are particularly important in
the control of tumor metastasis. The purpose of the proposed pilot study is
to investigate potential mediators that may account for stress-induced
reduction in NK cell activity. Cytokine activation is essential to optimal
NK cell activity and the adrenocortical stress hormones, cortisol and
dehydroepiandrostarons (DHEA), regulate the pattern of cytokine production.
Therefore, the role of Thl/Th2 cytokines in the psycho-andocrine and NK cell
response of women pro-and post-breast biopsy will be determined. The
psychological response will be measured by assessing mood disturbance,
perceived stress, and anxiety. Additionally, psychological constructs which
may modify stress perception will be measured and include, resilience and
sense of coherence. Stress-induced neuroendocrine activation and NK cell
activity will be evaluated in the context of these psychological measures.
A within groups design in which women experiencing heightened psychological
stress and low NK cell activity (pre- biopsy) followed by alleviation of
stress and restoration of NK cell activity (post-biopsy with benign results)
will be used to follow patterns of Thl /Th2 cytokines and plasma levels of
stress hormones. Potential differences in these responses in women with
benign versus those with malignant breast biopsy findings will be
determined. This study is unique in that it will provide an integrated
psycho-endocrine-immune profile of women early in the cancer trajectory, as
well as an understanding of the role of potential mediators of
stress-induced immune depression. An understanding of the mechanisms
underlying the stress-induced reduction of NKCA has considerable
implications not only for women undergoing breast biopsy, but most
importantly for the development and testing of interventions that can
prevent and/or control NK cell depression in women diagnosed with breast
cancer. Such intervention may improve the response to standard therapy,
improve symptom management, and hence the quality of life of women with
breast cancer.
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