Biobehavioral Factors, Stress and Cancer Progression: A Contemporary Review

Biobehavioral Factors Stress and Cancer
Biobehavioral Factors, Stress and Cancer

In two recent reviews, published in 2011, Erin Costanzo, Anil Sood and Susan Lutgendorf provide a contemporary overview of the major pathways involved in the cross-talk between behavioral factors and the immune system that contribute to cancer development  and progression.

The idea that psychological factors may contribute to cancer development and progression is not new. Galen, circa 200 A.D. wrote that that melancholic women were more prone to develop ‘swellings’ of the breasts than were sanguine women.

This idea dominated medicine for a long time. For example, the Byzantine physician Aetius hypothesized that tumors are the result of “melancholy accumulating in the brain”. Centuries later, Arabic physicians such as Avicena and Avenzoar similarly reported that the development of tumors was associated with a melancholy mood.

At the beginning of the 17th century, the French surgeon Claude Chapuys de Saint‐Amour noted in his Treatise on cancer, as occult as ulcerated that tumors are caused by grief, anger, and agitation. In the early 18th century, the French physician Claude Deshais Gendron pointed to a link between serious life situations and the incidence of cancer and  the effects of “disasters of life as occasion much trouble and grief” in the causation of cancer. In fact, throughout 18th and 19th century physicians had a firm belief that ‘stressful states’ predisposed to cancer.

In the early 20th century psychiatrists called attention to the link between cancer and personality traits, and concurrently investigators at Pavlov’s laboratory reported that experimental animals subjected to severe or chronic stress, had a marked tendency to develop malignancies. Furthermore, Sir William Osler reported the spontaneous shrinkage of metastases from breast cancer in two women in 1901 (cf. Paul Rosch, 1996).

Much more recently, evidence accumulated over the last 2-3 decades provides much clearer link between psychosocial and neurohormonal factors, and cancer development or progression. Epidemiologic data link cancer incidence with severe life events, severe distress, or long-term depression. A more consistent association has been observed between psychosocial risk factors such as depression, distress, trauma history, social isolation and more rapid cancer progression.

Importantly, several fundamental and clinical studies indicate that tumor tissue is innervated; neurohormonal mediators affect key components of tumor biology such as tumor growth, angiogenesis, migration or invasion, and that an altered activity of the nervous system influences tumor cell proliferation. Some of these studies, ideas and concepts are briefly outlined here, at

For more comprehensive information and reviews, see Rosch PJ, Stress and cancer: Disorders of communication, control, and civilization, 1996. In, Handbook of stress, medicine, and health (Boca Raton, FL, CRC Press);  Reiche EM et al., Lancet Oncol 2004, 10:617; Thaker PH and Sood AK, Semin Cancer Biol, 2008, 18:164; Moreno-Smith M et al., Future Oncol, 2010, 6:1863; Ondicova K and Mravec B, Lancet Oncol 2010, 11: 596.

The two recent reviews by Erin Costanzo, Anil Sood and Susan Lutgendorf focus mostly on contributions of behavioral factors to cancer progression and potential mechanisms underlying these relationships. Both direct effects of neuroendocrine factors on tumor growth, and indirect ones, through effects on the immune system, are discussed. The authors outline the following major mechanisms and pathways:

  • Behavioral pathways, stress hormones and immunosuppression, and the cellular immune response in cancer progression
  • Neurohormonal factors, angiogenesis and invasion; and stress-based modulation of angiogenesis
  • Stress effects on anoikis
  • Stress effects on stromal cells in the tumor microenvironment
  • Behavioral risk factors and tumor gene expression
  • Glucocorticoid dynamics and cancer progression
  • Behavioral factors and inflammation, and effects of inflammation on depression and quality of life

The information summarized in these reviews, indicates that there is compelling evidence that behavioral and psychosocial factors that activate the neuroendocrine stress response can alter immune, angiogenic, and inflammatory pathways, which play a major role in the development, progression, and control of malignancy.

The authors conclude with future directions, including sensitive populations and windows of opportunity. They suggest that a better understanding of biobehavioral mechanisms involved in cancer progression may improve the effectiveness of conventional therapies, put forward new pharmacological approaches and help the development of personalized therapy.

Immunol Allergy Clin North Am 2011, 31:109
Psychosom Med 2011, 73:724. Epub 2011 Oct 21

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