Current Breast Cancer Reports

, Volume 2, Issue 3, pp 130–137 | Cite as

The Relationship Between Psychosocial Stressors and Breast Cancer Biology

  • Amal Melhem-Bertrandt
  • Suzanne D. Conzen


Psychosocial stressors have been firmly linked to cardiovascular, immune, and metabolic disease risk through their effects on human physiology. An association with breast cancer risk has also been hypothesized, with both immune and endocrine-mediated mechanisms postulated to link stress to breast cancer biology. Several epidemiologic studies have been performed in an effort to better define the potential association between psychosocial stressors and breast cancer risk. However, despite large prospective studies, the question of whether or not psychosocial stress influences the risk and/or progression of breast cancer remains controversial. From an epidemiologic standpoint, evidence that chronic stress is linked to increased incidence of breast cancer is mixed, whereas targeted intervention trials suggest that reducing chronic stressors diminishes the risk of recurrence. Experimental approaches using animal studies have also yielded conflicting results depending on the model used. Nevertheless, the experimental studies offer valuable insights into environmental stressors and their potential mechanisms for altering the biology of well-defined breast cancer models. The ultimate goal of studying psychosocial stress and breast cancer biology is to identify the interacting mechanisms linking stress physiology to cancer and thereby to modify breast cancer risk factors.


Stress Breast cancer Incidence Progression Estrogen receptor Risk factors 



Supported by R01 CA89208-08 and the Breast SPORE P50 CA125183-04. We thank Ian Friedman for critical review of the manuscript and Susan Cadle for secretarial support.


No potential conflicts of interest relevant to this article were reported.


Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. 1.
    Figueredo VM: The time has come for physicians to take notice: the impact of psychosocial stressors on the heart. Am J Med 2009, 122:704–712.CrossRefPubMedGoogle Scholar
  2. 2.
    Wirtz PH, Ehler U, Bartschi C, et al.: Changes in plasma lipids with psychosocial stress are related to hypertension status and the norepinephrine stress response. Metabolism 2009, 58:30–37.CrossRefPubMedGoogle Scholar
  3. 3.
    Cohen S, Janicki-Deverts D, Miller GE: Psychological stress and disease. JAMA 2007, 298:1685–1687.CrossRefPubMedGoogle Scholar
  4. 4.
    Lillberg K, Verkasalo PK, Kaprio J, et al.: Stressful life events and risk of breast cancer in 10,808 women: a cohort study. Am J Epidemiol 2003, 157:415–423.CrossRefPubMedGoogle Scholar
  5. 5.
    Duijts SF, Zeegers MP, Borne BV: The association between stressful life events and breast cancer risk: a meta-analysis. Int J Cancer 2003, 107:1023–1029.CrossRefPubMedGoogle Scholar
  6. 6.
    Lambe M, Cerrato R, Askling J, et al.: Maternal breast cancer risk after the death of a child. Int J Cancer 2004, 110:763–766.CrossRefPubMedGoogle Scholar
  7. 7.
    Folkman S, Lazarus RS, Dunkel-Schetter C, et al.: Dynamics of a stressful encounter: cognitive appraisal, coping, and encounter outcomes. J Pers Soc Psychol 1986, 50:992–1003.CrossRefPubMedGoogle Scholar
  8. 8.
    Kroenke CH, Hankinson SE, Schernhammer ES, et al.: Caregiving stress, endogenous sex steroid hormone levels, and breast cancer incidence. Am J Epidemiol 2004, 159:1019–1027.CrossRefPubMedGoogle Scholar
  9. 9.
    Surtees PG, Wainwright NW, Luben RH, et al.: No evidence that social stress is associated with breast cancer incidence. Breast Cancer Res Treat 2010, 120:169–174.CrossRefPubMedGoogle Scholar
  10. 10.
    ••Michael YL, Carlson NE, Chlebowski RT, et al.: Influence of stressors on breast cancer incidence in the Women's Health Initiative. Health Psychol 2009, 28:137–146. This large study (n = 84,334) from the Women’s Health initiative showed that multiple, repeated stressful life events and lack of social support were unexpectedly associated with a decreased risk of breast cancer in post-menopausal women with the highest levels of reported stress. However, there was no analysis of risk by estrogen receptor subtype.Google Scholar
  11. 11.
    Nielsen NR, Zhang ZF, Kristensen TS, et al.: Self reported stress and risk of breast cancer: prospective cohort study. BMJ 2005, 331:548.CrossRefPubMedGoogle Scholar
  12. 12.
    Helgesson O, Cabrera C, Lapidus L, et al.: Self-reported stress levels predict subsequent breast cancer in a cohort of Swedish women. Eur J Cancer Prev 2003, 12:377–381.CrossRefPubMedGoogle Scholar
  13. 13.
    Kudielka BM, Hellhammer DH, Wust S: Why do we respond so differently? Reviewing determinants of human salivary cortisol responses to challenge. Psychoneuroendocrinology 2009, 34:2–18.CrossRefPubMedGoogle Scholar
  14. 14.
    Kananen L, Surakka I, Pirkola S, et al.: Childhood adversities are associated with shorter telomere length at adult age both in individuals with an anxiety disorder and controls. PLoS One 2010, 5:e10826.CrossRefPubMedGoogle Scholar
  15. 15.
    Barekati Z, Radpour R, Kohler C, et al.: Methylation profile of TP53 regulatory pathway and mtDNA alterations in breast cancer patients lacking TP53 mutations. Hum Mol Genet 2010 [Epub ahead of print].Google Scholar
  16. 16.
    Feder A, Nestler EJ, Charney DS: Psychobiology and molecular genetics of resilience. Nat Rev Neurosci 2009, 10:446–457.CrossRefPubMedGoogle Scholar
  17. 17.
    Sorlie T, Perou CM, Tibshirani R, et al.: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 2001, 98:10869–10874.CrossRefPubMedGoogle Scholar
  18. 18.
    Bauer K, Parise C, Caggiano V. Use of ER/PR/HER2 subtypes in conjunction with the 2007 St Gallen Consensus Statement for early breast cancer. BMC Cancer 2010, 10:228–239.Google Scholar
  19. 19.
    Kwan ML, Kushi LH, Weltzien E, et al.: Epidemiology of breast cancer subtypes in two prospective cohort studies of breast cancer survivors. Breast Cancer Res 2009, 11:R31.CrossRefPubMedGoogle Scholar
  20. 20.
    Missmer SA, Eliassen AH, Barbieri RL, Hankinson SE: Endogenous estrogen, androgen, and progesterone concentrations and breast cancer risk among postmenopausal women. J Natl Cancer Inst 2004, 96:1856–1865.CrossRefPubMedGoogle Scholar
  21. 21.
    Chrousos GP, Torpy DJ, Gold PW: Interactions between the hypothalamic-pituitary-adrenal axis and the female reproductive system: clinical implications. Ann Intern Med 1998, 129:229–240.PubMedGoogle Scholar
  22. 22.
    Ray M, Polite BN: Triple-negative breast cancers: a view from 10,000 feet. Cancer J 2010, 16:17–22.CrossRefPubMedGoogle Scholar
  23. 23.
    Spiegel D, Giese-Davis J: Depression and cancer: mechanisms and disease progression. Biol Psychiatry 2003, 54:269–282.CrossRefPubMedGoogle Scholar
  24. 24.
    Chida Y, Hamer M, Wardle J, Steptoe A: Do stress-related psychosocial factors contribute to cancer incidence and survival? Nat Clin Pract Oncol 2008, 5:466–475.CrossRefPubMedGoogle Scholar
  25. 25.
    Spiegel D, Butler LD, Giese-Davis J, et al.: Effects of supportive-expressive group therapy on survival of patients with metastatic breast cancer: a randomized prospective trial. Cancer 2007, 110:1130–1138.CrossRefPubMedGoogle Scholar
  26. 26.
    •• Andersen BL, Yang HC, Farrar WB, et al.: Psychologic intervention improves survival for breast cancer patients: a randomized clinical trial. Cancer 2008, 113:3450–3458. This randomized intervention trial (n = 227) revealed a reduced risk of recurrence and improved overall survival among women with early-stage breast cancer who were assigned to a psychological intervention versus an observation-only group. This study suggests that reduced stress exposure can reduce the microscopic metastases from becoming clinically significant.Google Scholar
  27. 27.
    Sapolsky RM, Donnelly TM: Vulnerability to stress-induced tumor growth increases with age in rats: role of glucocorticoids. Endocrinology 1985, 117:662–666.CrossRefPubMedGoogle Scholar
  28. 28.
    Antoni MH, Lutgendorf SF, Cole SW, et al.: The influence of bio-behavioural factors on tumour biology: pathways and mechanisms. Nat Rev Cancer 2006, 6:240–248.CrossRefPubMedGoogle Scholar
  29. 29.
    Chrousos GP: Stress and disorders of the stress system. Nat Rev Endocrinol 2009, 5:374–381.CrossRefPubMedGoogle Scholar
  30. 30.
    Pohlmann PR, Mayer IA, Mernaugh R: Resistance to trastuzumab in breast cancer. Clin Cancer Res 2009, 15:7479–7491.CrossRefPubMedGoogle Scholar
  31. 31.
    Steplewski Z, Vogel WH, Ehya H, et al.: Effects of restraint stress on inoculated tumor growth and immune response in rats. Cancer Res 1985, 45:5128–5133.PubMedGoogle Scholar
  32. 32.
    Ben-Eliyahu S, Page GG, Yirmiya R, Shakhar G: Evidence that stress and surgical interventions promote tumor development by suppressing natural killer cell activity. Int J Cancer 1999, 80:880–888.CrossRefPubMedGoogle Scholar
  33. 33.
    Stefanski V, Ben-Eliyahu S: Social confrontation and tumor metastasis in rats: defeat and beta-adrenergic mechanisms. Physiol Behav 1996, 60:277–282.CrossRefPubMedGoogle Scholar
  34. 34.
    Ben-Eliyahu S, Page GG, Shakhar G, Taylor AN: Increased susceptibility to metastasis during pro-oestrus/oestrus in rats: possible role of oestradiol and natural killer cells. Br J Cancer 1996, 74:1900–1907.PubMedGoogle Scholar
  35. 35.
    Biggar RJ, Kirby KA, Atkinson J, et al.: Cancer risk in elderly persons with HIV/AIDS. J Acquir Immune Defic Syndr 2004, 36:861–868.CrossRefPubMedGoogle Scholar
  36. 36.
    Engels EA, Biggar RJ, Hall HI et al.: Cancer risk in people infected with human immunodeficiency virus in the United States. Int J Cancer 2008, 123:187–194.CrossRefPubMedGoogle Scholar
  37. 37.
    Pierce BL, Ballard-Barbash R, Bernstein L, et al.: Elevated biomarkers of inflammation are associated with reduced survival among breast cancer patients. J Clin Oncol 2009, 27:3437–3444.CrossRefPubMedGoogle Scholar
  38. 38.
    DeNardo DG, Coussens LM: Inflammation and breast cancer. Balancing immune response: crosstalk between adaptive and innate immune cells during breast cancer progression. Breast Cancer Res 2007, 9:212.Google Scholar
  39. 39.
    •• Williams JB, Pang D, Delgado B, et al.: A model of gene-environment interaction reveals altered mammary gland gene expression and increased tumor growth following social isolation. Cancer Prev Res 2009, 2:850–861. Using a genetic mouse model of ER basal-type human breast cancer, this study examined chronic stress, the stress response, and mammary gland tumor biology. The authors found that stress from chronic social isolation is associated with increased mammary gland metabolic gene expression (lipid synthesis) and subsequently increased mammary tumor growth. These data suggest that neuroendocrine changes in response to chronic stressors may influence mammary gland biology and cancer growth through changes in lipid metabolism occurring in the premalignant mammary gland. Whether these changes occur in the mammary ductal epithelium, the stroma, or both remains to be determined.Google Scholar
  40. 40.
    Hermes GL, Rosenthal L, Montag A, McClintock MK: Social isolation and the inflammatory response: sex differences in the enduring effects of a prior stressor. Am J Physiol Regul Integr Comp Physiol 2006, 290:R273–R282.PubMedGoogle Scholar
  41. 41.
    Cavigelli SA, Yee JR, McClintock MK: Infant temperament predicts life span in female rats that develop spontaneous tumors. Horm Behav 2006, 50:454–462.CrossRefPubMedGoogle Scholar
  42. 42.
    Hermes GL, Delgado B, Tretiakova M, et al.: Social isolation dysregulates endocrine and behavioral stress while increasing malignant burden of spontaneous mammary tumors. Proc Natl Acad Sci U S A 2009, 106:22393–22398.CrossRefPubMedGoogle Scholar
  43. 43.
    Maroulakou IG, Anver M, Garrett L, Green JE: Prostate and mammary adenocarcinoma in transgenic mice carrying a rat C3(1) simian virus 40 large tumor antigen fusion gene. Proc Natl Acad Sci U S A 1994, 91:11236–11240.CrossRefPubMedGoogle Scholar
  44. 44.
    Goetz F, Tzeng YJ, Guhl E, et al.: The SV40 small t-antigen prevents mammary gland differentiation and induces breast cancer formation in transgenic mice; truncated large T-antigen molecules harboring the intact p53 and pRb binding region do not have this effect. Oncogene 2001, 20:2325–2332.CrossRefPubMedGoogle Scholar
  45. 45.
    Hasen NS, O’Leary KA, Auger AP, Schuler LA: Social isolation reduces mammary development, tumor incidence, and expression of epigenetic regulators in wild-type and p53-heterozygotic mice. Cancer Prev Res 2010, 3:620–629.CrossRefGoogle Scholar
  46. 46.
    Yoshidome K, Shibata MA, Couldrey C, et al.: Estrogen promotes mammary tumor development in C3(1)/SV40 large T-antigen transgenic mice: paradoxical loss of estrogen receptoralpha expression during tumor progression. Cancer Res 2000, 60:6901–6910.PubMedGoogle Scholar
  47. 47.
    Thaker PH, Han LY, Kamat AA, et al.: Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma. Nat Med 2006, 12:939–944.CrossRefPubMedGoogle Scholar
  48. 48.
    Powe DG, Groot Kormelink T, Sisson M, et al.: Beta-blocker treatment is associated with a reduction in tumor metastasis and an improvement in specific survival in patients with breast cancer. Eur J Cancer Suppl 2010, 8:188.Google Scholar
  49. 49.
    Lillberg K, Verkasalo PK, Kaprio J, et al.: Stress of daily activities and risk of breast cancer: a prospective cohort study in Finland. Int J Cancer 2001, 91:888–893.CrossRefPubMedGoogle Scholar
  50. 50.
    Saez Mdel C, Barriga C, Garcia JJ, et al.: Exercise-induced stress enhances mammary tumor growth in rats: beneficial effect of the hormone melatonin. Mol Cell Biochem 2007, 294:19–24.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Breast Medical OncologyMD Anderson Cancer CenterHoustonUSA
  2. 2.Department of MedicineThe University of ChicagoChicagoUSA

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