Previous research with animal models has compellingly demonstrated that: 1) experimental exposures to various stressors (e.g., electric shock) have multiple effects on the immune system, including reductions in natural killer (NK) cell activity; 2) exposures to stressors prior to intravenous injection with live tumor cells results in reduced tumor clearance, increased metastases, and increased mortality; and 3) these effects of stressor exposure on metastatic risk are mediated by stress-induced suppression of NK cell activity. The relevance of this extensive preclinical research literature to human cancer is currently unknown. The goal of the two year research study proposed in this exploratory/development grant application is to investigate the impact of presurgery stress on two variables identified as potential predictors of cancer patients' subsequent risk of developing metastatic disease: presurgery levels of NK cell activity (and related immune variables) and surgery-related dissemination of tumor cells in the blood stream. Specific Aim l: To investigate the patterns and predictors of presurgical stress levels among women scheduled for surgical treatment of primary breast cancer, using a longitudinal between-subjects research design. Patients (n=100) with breast cancer will be assessed on 4 occasions prior to outpatient surgery: Day-7, Day-2, Day-1 (in their homes) and Day-0 (in the clinic prior to medication for surgery). Psychobiological assessments of stress will include: self-report, cardiovascular, and endocrine measures. Responses will be contrasted to those of two matched Comparison Groups: l) patients (n=50) with benign breast disease scheduled for surgery; and, 2) healthy women from the community not undergoing surgery (n=50). Specific Aim 2: To examine the patterns and predictors of presurgical levels of NK cell activity and related immune measures in women scheduled for surgical treatment of breast cancer using a longitudinal between-subjects research design. At each of the presurgery assessments described above, blood samples will be taken for assay of immune measures. Specific Aim 3: To explore the patterns and predictors of pre- and peri- operative levels of breast cancer cells in the blood stream of women scheduled for surgical treatment of primary breast cancer, using a longitudinal between-subjects research design. Blood collection on Day-6 and Day-0 will include samples for assessment of the numbers of breast cancer cells in circulation, using an extremely sensitive reverse- transcriptase polymerase chain reaction (RT-PCR) with a newly identified, highly specific marker (mammaglobin). On Day-0, two additional samples will be collected - one during and one after-surgery - to provide some preliminary indication of the relative contribution of physical stresses to tumor cell dissemination above and beyond preoperative Psychobiological stress.
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