Stressors, Stress Response, and Cancer Recurrence

A Systematic Review

Briana L. Todd, MA, MS; Michal C. Moskowitz, MS; Alicia Ottati, MA; Michael Feuerstein, PhD, MPH

Disclosures

Cancer Nurs. 2014;37(2):114-125. 

In This Article

Abstract and Introduction

Abstract

Background: Cancer survivors assume that stress plays an important role in cancer recurrence. However, the role of stress in the etiology of cancer recurrence remains unclear.

Objective: A systematic review examining the causal role of exposure to stressors and/or stress response and cancer recurrence was conducted.

Methods: The authors screened the scientific literature published from December 1979 through April 2012. Prospective studies and randomized control trials that examined the link between exposure to stressors and/or stress response and cancer recurrence were included in the review.

Results: Fifteen studies examined exposures to stressors (life event questionnaires) and/or multiple indices of the stress response (mood, anxiety, depression, biological, and immune measures). The relationships between stressors and/or stress response and recurrence were observed as no relationship (80%), positive relationship (33%), and inverse relationship (27%). One of 3 randomized control trials reported a positive relationship between stress reduction and reduced risk of recurrence.

Conclusions: The scientific literature to date indicates no clear evidence for a causal relationship between stress (measured as stressor exposure and/or stress response) and cancer recurrence. Although additional high-quality research is needed to provide a more definitive answer, the evidence to date does not support this hypothesis.

Introduction

Implications for Practice: Although at present, there is no evidence indicating a causal relationship between stress and cancer recurrence, attending to the reduction in a cancer survivor's stress response can improve emotional well-being and quality of life.

Even after completion of primary treatment, with tests indicating no evidence of disease, cancer survivors grapple with the prospect of a recurrence. In breast cancer survivors, for example, 5-year recurrence rates may range widely from less than 1% to greater than 55% depending on age at diagnosis, type of treatment received, and diagnostic variables such as stage, lymph node involvement, and hormone receptor status.[1,2] Fear of recurrence is highly prevalent in cancer survivors, even several years after completion of primary treatment, and is associated with poorer quality of life and well-being.[3,4] Several years after diagnosis, uncertainty about recurrence can be triggered by several factors, including environmental stimuli, physical symptoms, or hearing about someone else's cancer.[5]

Nurses and other healthcare providers report being asked by patients about lifestyle factors that cause cancer and can prevent recurrence.[6] Many cancer survivors assume that stress plays an important role in the risk of cancer recurrence.[7–9] When asked about factors preventing recurrence, between 28% and 78% of breast and gynecological cancer survivors cited stress reduction as important.[7–9] A link between stress and primary development of cancer also has caught the imagination of the public and has become a common belief.[10] A study of testicular cancer survivors (N = 316) found that attributing one's cancer to psychological stress, which was reported by 17% of the sample, was associated with higher fear of recurrence (odds ratio, 2.57; 95% confidence interval, 1.40–4.73).[11]

Before addressing the question of whether stress is linked to cancer recurrence, an examination of the term stress is warranted. There is no gold standard definition of stress in human health. Stress is often assessed and measured in 3 broad ways: environmental, psychological, and biological.[12] Environmental assessments of stress measure factors outside of the individual, focusing instead on objective exposure to stressors, that is, life events that are commonly perceived as stressful.[12] Such measurement may include the occurrence of acute stressors, such as death of a loved one, divorce, illness, or job loss,[13] or the existence of recurrent or chronic stressors, such as work stress and marital discord.[14] The psychological conceptualization of stress, in contrast, focuses on the individual's subjective response to stress. Lazarus et al[15,16] developed this conceptualization by proposing a cognitive model in which the individual perceives potentially stressful stimuli and determines whether they constitute a threat or challenge. Perception of threatening stimuli activates a stress response that often consists of emotional (eg, negative mood), behavioral (eg, sleep, drinking, smoking), and physiological changes. The physiological stress response entails activation of the hypothalamic-pituitary-adrenocortical (HPA) axis and sympathetic nervous system (SNS),[12] which in turn modulate cellular immune responses such as natural killer cell activity.[17] Biological measurements of stress may assess indicators of HPA or SNS activity (eg, cortisol, catecholamines) or immune activity that are modulated by the stress response.

A potential link between stress and cancer progression would be consistent with a biobehavioral conceptual model of cancer.[17] The perception of stress activates the HPA axis and SNS, which can modulate cellular immune responses that can disrupt physiological processes in tumor surveillance and containment, which may in turn encourage tumor progression or recurrence.[17] Exposure to stressors has long been hypothesized to play a role in the recurrence of tumor activity,[18] and some investigators have proposed that exposure to psychological stressors plays a larger role in cancer recurrence than cancer incidence.[17] However, the role of stressors in the etiology of cancer remains unclear.[19] Numerous studies attempting to examine the link between stress and cancer onset have produced conflicting results.[19–21]

Nurses and other healthcare providers report some reluctance in advising patients about lifestyle factors associated with the prevention of recurrence, in part because of confusion about contradictory findings in the literature.[6] Although the hypothetical link between stress and recurrence is one held by many cancer survivors and is biologically plausible, the evidence for such a causal relationship has not been previously systematically reviewed. It is unknown whether stress is indeed positively associated with higher risk of recurrence, or whether stress reduction reduces the risk of recurrence. The purpose of this article was to address the following question: Does stress—measured in environmental, psychological, and/or biological terms—predict the subsequent recurrence of cancer over time? To answer this question, the authors conducted a systematic review of prospective longitudinal human studies and randomized controlled trials measuring stress and recurrence.

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