MYTH: “Stress is stress. It’s annoying, but it’s not harmful.”
TRUTH: We are all exposed to stress in varying degrees during our daily lives, and everyone responds to stress differently. It has become easy in our highly motivated society to flippantly offer how stressed we are, yet to continue to move on with our day. I think we assume that stress is inevitable and that it is a natural sequela of our profession. But, I think we also fail to realize that stress can affect us not only emotionally but physiologically as well.
A recent meta-analysis published in the J Exp Clin Cancer Research in 2013 (1) showed a significant association between striking life events (divorce/separation, death of husband, and death of close friend/relative) and breast cancer incidence. Results from the Finnish Twin Cohort Study (2) also found a relation between the accumulation of life events and an increased risk of breast cancer among genetically identical twins. Adjustment for relative risk factors (including age at first child birth and parity) did not alter this finding. This is a relatively strong study given that it was a prospective population-based study and the twins in each pair had the same genetic make-up and childhood environments. Eliminating estrogen-related variables, a Wisconsin Longitudinal Study following 3,682 women between the ages of 36 and 72 also demonstrated that women in professional occupations and positions of authority had 57-89% higher risk of breast cancer development (3).
So, it is true that stress can increase risk for cancer development by altering physiology. Putative explanations for the adverse effects of stress include changes in the production of the adrenocorticoid, cortisol, which has been shown to have inhibitory effects on the most well-established tumor suppressor gene, p53 (4). Activation of the glucocorticoid receptor has also been shown to stimulate breast cell proliferation. And, more recently, there has been interesting suggestions that stress can act in a manner that is hormone-independent.
Two new hypotheses have emerged that suggest a direct effect on key genes. Researchers from the University of Chicago reported in July 2013 that the “triple-negative” mouse raised in a chronic stress situation had a dramatic change in the expression of three key genes by mammary fat cells as well as development of larger and more aggressive cancers (5). Circulating hormone levels were measured and were not different, but the expression of key genes in mammary fat cells (and no other cell type) was dramatically altered. These fat cells appear to exert a paracrine effect on neighboring breast epithelial cells, causing more rapid cellular proliferation. Perhaps this hints at another link between fat and breast cancer.
Finally, a new study in the Journal of Clinical Investigation suggests that activation of the gene ATF3 in immune cells by neighboring breast cancer cells enhances cancer metastases and leads to poorer survival. ATF3 is known as the “stress gene”, and is expressed in response to stressful situations. Signals sent by cancer cells to immune cells, high-fat diet, UV damage, chronic stress and other factors have been shown to activate ATF3 (6).
BOTTOMLINE: As part of our goal of restoring health while treating disease, we recognize the role of stress in breast cancer development and are engaged in developing a Yoga Program at the Margie Petersen Breast Center for our patients undergoing breast cancer treatment. Yoga has undergone scientific study and has been found in human studies to positively affect levels of monoamines, melatonin, cortisol and GABA, which has been linked to decrease stress. For more information on how you can support the Yoga Program, please see our announcement in this newsletter.
- Lin Y, Wang, C, Zhong Y et al. Striking life events associated with primary breast cancer susceptibility in women: a meta-analysis study. J Exp Clin Cancer Res 2013;32:53-61.
- 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.
- Pudrovska T, Carr D, McFarland M, et al. Social Science and Medicine 2013; 89:53-61.
- Feng et al. Chronic restraint stress attenuates p53 function and promotes tumorigenesis. PNAS 2012;109(18):7013-7018.
- Volden PA, Wonder EL, Skor MN, et al. Chronic social isolation is associated with metabolic gene expression changes specific to mammary adipose tissue. Cancer Prev Res 2013;6(7):634-645.
- Wolford CC, McConoughey SJ, Jalgaonkar SP, et al. Transcription factor ATF3 links host adaptive response to breast cancer metastasis. J Clin Invest 2013;123(7):2893-2906.