Breast Cancer Risk and Immune Responses in Healthy Women

Na-Jin Park RN, PhD

Duck-Hee Kang

ONF 2006, 33(6), 1151-1159. DOI: 10.1188/06.ONF.1151-1159

Purpose/Objectives: To summarize the findings of objective and subjective breast cancer risk assessments and their association with psychological distress and immune responses in healthy women with a family history of breast cancer.

Data Sources: Published articles and book chapters.

Data Synthesis: Healthy women with a family history of breast cancer have shown decreased immune responses (i.e., low natural killer cell activity and low Th1 cytokine production), exaggerated biophysiologic reactivity to stimuli, and increased psychological distress.

Conclusions: Objective and subjective breast cancer risk is associated with impaired immune responses and exaggerated biophysiologic responses in healthy women with a family history of breast cancer. Increased psychological distress can contribute further to negative immune responses. Additional studies are warranted to substantiate and extend the findings based on more comprehensive assessments of objective and subjective breast cancer risk.

Implications for Nursing: Biophysiologic assessment is a useful approach for nurses in early identification of women at risk for breast cancer and developing appropriate strategies to reduce the risk.

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    American Cancer Society. (2006). Cancer facts and figures 2006. Atlanta, GA: Author.

    Andersen, B.L., Farrar, W.B., Golden-Kreutz, D., Kutz, L.A., MacCallum, R., Courtney, M.E., et al. (1998). Stress and immune responses after surgical treatment for regional breast cancer. Journal of the National Cancer Institute, 90, 30-36.

    Andersen, B.L., Kiecolt-Glaser, J.K., & Glaser, R. (1994). A biobehavioral model of cancer stress and disease course. American Psychologist, 49, 389-404.

    Antoniou, A.C., Pharoah, P.D., McMullan, G., Day, N.E., Stratton, M.R., Peto, J., et al. (2002). A comprehensive model for familial breast cancer incorporating BRCA1, BRCA2 and other genes. British Journal of Cancer, 86, 76-83.

    Antoniou, A.C., Pharoah, P.D., Smith, P., & Easton, D.F. (2004). The BOADICEA model of genetic susceptibility to breast and ovarian cancer. British Journal of Cancer, 91, 1580-1590.

    Arduino, S., Tessarolo, M., Bellino, R., Colombatto, S., Leo, L., Wierdis, T., et al. (1996). Reduced IL-2 level concentration in patients with breast cancer as a possible risk factor for relapse. European Journal of Gynaecological Oncology, 17, 535-537.

    Armstrong, K., Eisen, A., & Weber, B. (2000). Assessing the risk of breast cancer. New England Journal of Medicine, 342, 564-571.

    Baltzell, K., & Wrensch, M.R. (2005). Strengths and limitations of breast cancer risk assessment. Oncology Nursing Forum, 32, 605-616.

    Baxevanis, C.N., Reclos, G.J., Gritzapis, A.D., Dedousis, G.V., Missitzis, I., & Papamichail, M. (1993). Elevated prostaglandin E2 production by monocytes is responsible for the depressed levels of natural killer and lymphokine-activated killer cell function in patients with breast cancer. Cancer, 72, 491-501.

    Bondy, M.L., & Newman, L.A. (2003). Breast cancer risk assessment models: Applicability to African-American women. Cancer, 97(1, Suppl.), 230-235.

    Bovbjerg, D.H., & Valdimarsdottir, H. (1993). Familial cancer, emotional distress, and low natural cytotoxic activity in healthy women. Annals of Oncology, 4, 745-752.

    Bovbjerg, D.H., & Valdimarsdottir, H.B. (2001). Interventions for healthy individuals at familial risk for cancer: Biobehavioral mechanisms for health benefits. In A. Baum & B.L. Andersen (Eds.), Psychosocial interventions for cancer (pp. 305-320). Washington, DC: American Psychological Association.

    Brittenden, J., Heys, S.D., Ross, J., & Eremin, O. (1996). Natural killer cells and cancer. Cancer, 77, 1226-1243.

    Brown, P. (2005). Risk assessment: Controversies and management of moderate- to high-risk individuals. Breast Journal, 11(Suppl. 1), S11-S19.

    Cacioppo, J.T., Burleson, M.H., Poehlmann, K.M., Malarkey, W.B., Kiecolt-Glaser, J.K., Berntson, G.G., et al. (2000). Autonomic and neuroendocrine responses to mild psychological stressors: Effects of chronic stress on older women. Annals of Behavioral Medicine, 22, 140-148.

    Campbell, M.J., Scott, J., Maecker, H.T., Park, J.W., & Esserman, L.J. (2005). Immune dysfunction and micrometastases in women with breast cancer. Breast Cancer Research and Treatment, 91, 163-171.

    Champion, V.L. (1999). Revised susceptibility, benefits, and barriers scale for mammography screening. Research in Nursing and Health, 22, 341-348.

    Claus, E.B., Risch, N., & Thompson, W.D. (1994). Autosomal dominant inheritance of early-onset breast cancer: Implications for risk prediction. Cancer, 73, 643-651.

    Cohen, M., Klein, E., Kuten, A., Fried, G., Zinder, O., & Pollack, S. (2002). Increased emotional distress in daughters of breast cancer patients is associated with decreased natural cytotoxic activity, elevated levels of stress hormones, and decreased secretion of Th1 cytokines. International Journal of Cancer, 100, 347-354.

    Cohen, M., & Pollack, S. (2005). Mothers with breast cancer and their adult daughters: The relationship between mothers' reaction to breast cancer and their daughters' emotional and neuroimmune status. Psychosomatic Medicine, 67, 64-71.

    Cohen, S. (1994). Psychosocial influences on immunity and infectious disease in humans. In R. Glaser & J. Kiecolt-Glaser (Eds.), Handbook of human stress and immunity (pp. 301-319). San Diego, CA: Academic Press.

    Davids, S.L., Schapira, M.M., McAuliffe, T.L., & Nattinger, A.B. (2004). Predictors of pessimistic breast cancer risk perceptions in a primary care population. Journal of General Internal Medicine, 19, 310-315.

    Del Prete, G., Maggi, E., & Romagnani, S. (1994). Human Th1 and Th2 cells: Functional properties, mechanisms of regulation, and role in disease. Laboratory Investigation, 70, 299-306.

    Dettenborn, L., James, G.D., van Berge-Landry, H., Valdimarsdottir, H.B., Montgomery, G.H., & Bovbjerg, D.H. (2005). Heightened cortisol responses to daily stress in working women at familial risk for breast cancer. Biological Psychology, 69, 167-179.

    Domchek, S.M., Eisen, A., Calzone, K., Stopfer, J., Blackwood, A., & Weber, B.L. (2003). Application of breast cancer risk prediction models in clinical practice. Journal of Clinical Oncology, 21, 593-601.

    Dubey, D.P., Alper, C.A., Mirza, N.M., Awdeh, Z., & Yunis, E.J. (1994). Polymorphic Hh genes in the HLA-B(C) region control natural killer cell frequency and activity. Journal of Experimental Medicine, 179, 1193-1203.

    Erblich, J., Bovbjerg, D.H., & Valdimarsdottir, H.B. (2000). Looking forward and back: Distress among women at familial risk for breast cancer. Annals of Behavioral Medicine, 22, 53-59.

    Erblich, J., Montgomery, G.H., Valdimarsdottir, H.B., Cloitre, M., & Bovbjerg, D.H. (2003). Biased cognitive processing of cancer-related information among women with family histories of breast cancer: Evidence from a cancer stroop task. Health Psychology, 22, 235-244.

    Euhus, D.M. (2001). Understanding mathematical models for breast cancer risk assessment and counseling. Breast Journal, 7, 224-232.

    Gail, M.H., Brinton, L.A., Byar, D.P., Corle, D.K., Green, S.B., Schairer, C., et al. (1989). Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. Journal of the National Cancer Institute, 81, 1879-1886.

    Garssen, B., & Goodkin, K. (1999). On the role of immunological factors as mediators between psychosocial factors and cancer progression. Psychiatry Research, 85, 51-61.

    Gold, S.M., Zakowski, S.G., Valdimarsdottir, H.B., & Bovbjerg, D.H. (2003). Stronger endocrine responses after brief psychological stress in women at familial risk of breast cancer. Psychoneuroendocrinology, 28, 584-593.

    Goldsby, R.A., Kindt, T.J., & Osborne, B.A. (2000). Kuby immunology (4th ed.). New York: W.H. Freeman.

    Hersey, P., Edwards, A., Honeyman, M., & McCarthy, W.H. (1979). Low natural-killer-cell activity in familial melanoma patients and their relatives. British Journal of Cancer, 40, 113-122.

    Hoskins, K.F., Stopfer, J.E., Calzone, K.A., Merajver, S.D., Rebbeck, T.R., Garber, J.E., et al. (1995). Assessment and counseling for women with a family history of breast cancer: A guide for clinicians. JAMA, 273, 577-585.

    Hutson, S.P. (2003). Attitudes and psychological impact of genetic testing, genetic counseling, and breast cancer risk assessment among women at increased risk. Oncology Nursing Forum, 30, 241-246.

    James, G.D., van Berge-Landry, H., Valdimarsdottir, H.B., Montgomery, G.H., & Bovbjerg, D.H. (2004). Urinary catecholamine levels in daily life are elevated in women at familial risk of breast cancer. Psychoneuroendocrinology, 29, 831-838.

    Kang, D.H. (2003). Psychoneuroimmunology in nursing research: A biobehavioral model. Research in Nursing and Health, 26, 421-423.

    Kang, D.H., & Fox, C. (2001). Th1 and Th2 cytokine responses to academic stress. Research in Nursing and Health, 24, 245-257.

    Kerber, R.A., & Slattery, M.L. (1997). Comparison of self-reported and database-linked family history of cancer data in a case-control study. American Journal of Epidemiology, 146, 244-248.

    Kiecolt-Glaser, J.K., & Glaser, R. (1997). Measurement of immune response. In S. Cohen, R.C. Kessler, & L.U. Gordon (Eds.), Measuring stress: A guide for health and social scientists (pp. 213-229). New York: Oxford University Press.

    Kiecolt-Glaser, J.K., McGuire, L., Robles, T.F., & Glaser, R. (2002). Psychoneuroimmunology: Psychological influences on immune function and health. Journal of Consulting and Clinical Psychology, 70, 537-547.

    Kiecolt-Glaser, J.K., Robles, T.F., Heffner, K.L., Loving, T.J., & Glaser, R. (2002). Psycho-oncology and cancer: Psychoneuroimmunology and cancer. Annals of Oncology, 13(Suppl. 4), 165-169.

    Kim, Y., Duhamel, K.N., Valdimarsdottir, H.B., & Bovbjerg, D.H. (2005). Psychological distress among healthy women with family histories of breast cancer: Effects of recent life events. Psycho-Oncology, 14, 555-563.

    Konjevic, G., & Spuzic, I. (1993). Stage dependence of NK cell activity and its modulation by interleukin 2 in patients with breast cancer. Neoplasma, 40, 81-85.

    Kovacs, E., & Almendral, A. (1987). Reduced DNA repair synthesis in healthy women having first degree relatives with breast cancer. European Journal of Cancer and Clinical Oncology, 23, 1051-1057.

    Lancaster, D.R. (2005). Coping with appraised breast cancer risk among women with family histories of breast cancer. Research in Nursing and Health, 28, 144-158.

    Lazarus, R.S., & Folkman, S. (1984). Stress, appraisal, and coping. New York: Springer.

    Loescher, L.J. (1999). The family history component of cancer genetic risk counseling. Cancer Nursing, 22, 96-102.

    Mahon, S.M. (1998). Cancer risk assessment: Conceptual considerations for clinical practice. Oncology Nursing Forum, 25, 1535-1547.

    McCance, K.L., & Jorde, L.B. (1998). Evaluating the genetic risk of breast cancer. Nurse Practitioner, 23(8), 14-27.

    McEwen, B.S. (1998). Protective and damaging effects of stress mediators. New England Journal of Medicine, 338, 171-179.

    Meiser, B., Butow, P., Barratt, A., Gattas, M., Gaff, C., Haan, E., et al. (2001). Risk perceptions and knowledge of breast cancer genetics in women at increased risk of developing hereditary breast cancer. Psychology and Health, 16, 297-311.

    Merendino, R.A., Gangemi, S., Misefari, A., Arena, A., Capozza, A.B., Chillemi, S., et al. (1999). Interleukin-12 and interleukin-10 production by mononuclear phagocytic cells from breast cancer patients. Immunology Letters, 68, 355-358.

    Mouchawar, J., Byers, T., Cutter, G., Dignan, M., & Michael, S. (1999). A study of the relationship between family history of breast cancer and knowledge of breast cancer genetic testing prerequisites. Cancer Detection and Prevention, 23, 22-30.

    Parent, M.E., Ghadirian, P., Lacroix, A., & Perret, C. (1997). The reliability of recollections of family history: Implications for the medical provider. Journal of Cancer Education, 12, 114-120.

    Parmigiani, G., Berry, D., & Aguilar, O. (1998). Determining carrier probabilities for breast cancer-susceptibility genes BRCA1 and BRCA2. American Journal of Human Genetics, 62, 145-158.

    Parshad, R., Price, F.M., Bohr, V.A., Cowans, K.H., Zujewski, J.A., & Sanford, K.K. (1996). Deficient DNA repair capacity, a predisposing factor in breast cancer. British Journal of Cancer, 74, 1-5.

    Pasacreta, J.V. (1999). Psychosocial issues associated with increased breast and ovarian cancer risk: Findings from focus groups. Archives of Psychiatric Nursing, 13, 127-136.

    Paul, W.E., & Seder, R.A. (1994). Lymphocyte responses and cytokines. Cell, 76, 241-251.

    Pharoah, P.D., Day, N.E., Duffy, S., Easton, D.F., & Ponder, B.A. (1997). Family history and the risk of breast cancer: A systematic review and meta-analysis. International Journal of Cancer, 71, 800-809.

    Pharoah, P.D., Lipscombe, J.M., Redman, K.L., Day, N.E., Easton, D.F., & Ponder, B.A. (2000). Familial predisposition to breast cancer in a British population: Implications for prevention. European Journal of Cancer, 36, 773-779.

    Pharoah, P.D., Stratton, J.F., & Mackay, J. (1998). Screening for breast and ovarian cancer: The relevance of family history. British Medical Bulletin, 54, 823-838.

    Pike, J.L., Smith, T.L., Hauger, R.L., Nicassio, P.M., Patterson, T.L., McClintick, J., et al. (1997). Chronic life stress alters sympathetic, neuroendocrine, and immune responsivity to an acute psychological stressor in humans. Psychosomatic Medicine, 59, 447-457.

    Pross, H.F., & Lotzova, E. (1993). Role of natural killer cells in cancer. Natural Immunity, 12, 279-292.

    Rao, N.M., Joshi, N.N., Shinde, S.R., Advani, S.H., & Ghosh, S.N. (1996). Premature separation of centromere and aneuploidy: An indicator of high risk in unaffected individuals from familial breast cancer families? European Journal of Cancer Prevention, 5, 343-350.

    Rao, N.M., Pai, S.A., Shinde, S.R., & Ghosh, S.N. (1998). Reduced DNA repair capacity in breast cancer patients and unaffected individuals from breast cancer families. Cancer Genetics and Cytogenetics, 102, 65-73.

    Rebbeck, T.R. (1999). Inherited genetic predisposition in breast cancer: A population-based perspective. Cancer, 86(11, Suppl.), 2493-2501.

    Rhodes, D.J. (2002). Identifying and counseling women at increased risk for breast cancer. Mayo Clinic Proceedings, 77, 355-361.

    Sachs, G., Rasoul-Rockenschaub, S., Aschauer, H., Spiess, K., Gober, I., Staffen, A., et al. (1995). Lytic effector cell activity and major depressive disorder in patients with breast cancer: A prospective study. Journal of Neuroimmunology, 59, 83-89.

    Sakorafas, G.H., Krespis, E., & Pavlakis, G. (2002). Risk estimation for breast cancer development: A clinical perspective. Surgical Oncology, 10, 183-192.

    Segerstrom, S.C., & Miller, G.E. (2004). Psychological stress and the human immune system: A meta-analytic study of 30 years of inquiry. Psychological Bulletin, 130, 601-630.

    Shevde, L.A., Joshi, N.N., Advani, S.H., & Nadkarni, J.J. (1998). Impaired T lymphocyte function and differential cytokine response pattern in members from cancer families. Natural Immunity, 16, 146-156.

    Shevde, L.A., Joshi, N.N., Dudhat, S.B., Hawaldar, R.W., & Nadkarni, J.J. (1999). Immune functions, clinical parameters and hormone receptor status in breast cancer patients. Journal of Cancer Research and Clinical Oncology, 125, 313-320.

    Shevde, L.A., Joshi, N.N., Shinde, S.R., & Nadkarni, J.J. (1998). Studies on functional status of circulating lymphocytes in unaffected members from cancer families. Human Immunology, 59, 373-381.

    Shevde, L.A., Rao, N.M., Joshi, N.N., Shinde, S.R., Ghosh, S.N., & Nadkarni, J.J. (1998). Natural killer cell function and genetic instability in unaffected individuals from breast cancer families. European Journal of Cancer Prevention, 7, 141-148.

    Slattery, M.L., & Kerber, R.A. (1993). A comprehensive evaluation of family history and breast cancer risk: The Utah population database. JAMA, 270, 1563-1568.

    Slovic, P. (1987). Perception of risk. Science, 236, 280-285.

    Spaner, D., Radvanyi, L., & Miller, R.G. (1998). Immunology related to cancer. In I.F. Tannock & R.P. Hill (Eds.), The basic science of oncology (3rd ed., pp. 240-262). New York: McGraw-Hill.

    Sredni, B., Tichler, T., Shani, A., Catane, R., Kaufman, B., Strassmann, G., et al. (1996). Predominance of Th1 response in tumor-bearing mice and cancer patients treated with AS101. Journal of the National Cancer Institute, 88, 1276-1284.

    Strayer, D.R., Carter, W.A., & Brodsky, I. (1986). Familial occurrence of breast cancer is associated with reduced natural killer cytotoxicity. Breast Cancer Research and Treatment, 7, 187-192.

    Strayer, D.R., Carter, W.A., Mayberry, S.D., Pequignot, E., & Brodsky, I. (1984). Low natural cytotoxicity of peripheral blood mononuclear cells in individuals with high familial incidences of cancer. Cancer Research, 44, 370-374.

    Thull, D.L., & Farengo-Clark, D. (2003). Genetics of breast cancer. In V.G. Vogel & T. Bevers (Eds.), Handbook of breast cancer risk-assessment: Evidence-based guidelines for evaluation, prevention, counseling, and treatment (pp. 20-40). Sudbury, MA: Jones and Bartlett.

    Tjemsland, L., Soreide, J.A., Matre, R., & Malt, U.F. (1997). Pre-operative psychological variables predict immunological status in patients with operable breast cancer. Psycho-Oncology, 6, 311-320.

    Trinchieri, G. (1989). Biology of natural killer cells. Advances in Immunology, 47, 187-376.

    Valdimarsdottir, H.B., Bovbjerg, D.H., Kash, K.M., Holland, J.C., Osborne, M.P., & Miller, D.G. (1995). Psychological distress in women with a familial risk of breast cancer. Psycho-Oncology, 4, 133-141.

    Valdimarsdottir, H.B., Zakowski, S.G., Gerin, W., Mamakos, J., Pickering, T., & Bovbjerg, D.H. (2002). Heightened psychobiological reactivity to laboratory stressors in healthy women at familial risk for breast cancer. Journal of Behavioral Medicine, 25, 51-65.

    van Dooren, S., Rijnsburger, A.J., Seynaeve, C., Duivenvoorden, H.J., Essink- Bot, M.L., Tilanus-Linthorst, M.M., et al. (2004). Psychological distress in women at increased risk for breast cancer: The role of risk perception. European Journal of Cancer, 40, 2056-2063.

    Whiteside, T.L., & Herberman, R.B. (1995). The role of natural killer cells in immune surveillance of cancer. Current Opinion in Immunology, 7, 704-710.

    Wiltschke, C., Krainer, M., Budinsky, A.C., Berger, A., Muller, C., Zeillinger, R., et al. (1995). Reduced mitogenic stimulation of peripheral blood mononuclear cells as a prognostic parameter for the course of breast cancer: A prospective longitudinal study. British Journal of Cancer, 71, 1292-1296.

    Zakowski, S.G., Valdimarsdottir, H.B., Bovbjerg, D.H., Borgen, P., Holland, J., Kash, K., et al. (1997). Predictors of intrusive thoughts and avoidance in women with family histories of breast cancer. Annals of Behavioral Medicine, 19, 362-369.

    Zorrilla, E.P., Luborsky, L., McKay, J.R., Rosenthal, R., Houldin, A., Tax, A., et al. (2001). The relationship of depression and stressors to immunological assays: A meta-analytic review. Brain, Behavior, and Immunity, 15, 199-226.