Stress and Tumor Biology: Insights Into Managing Stress to Help Improve Cancer Care


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Lorenzo Cohen, PhD

Patients often ask which mind-body program is the best for reducing stress and improving quality of life. The answer is the one they will do every day and make a part of their life.

—Lorenzo Cohen, PhD, Anil K. Sood, MD, PhD, Sarah Prinsloo, PhD, and Alejandro Chaoul, PhD

Stress is ubiquitous in our society, especially for people diagnosed with a life-threatening illness. There is a common misconception that stress is derived from a particular negative event. However, the event itself (the stressors, such as cancer diagnoses and treatment) does not causes stress. Rather, the cause is the response to the stressor, known as the “fight-or-flight” response.

Although it is not always possible to control the stressors encountered in life, it is possible to learn how to control reactions to stressors. Ensuring that patients manage stress effectively is critical to improving patient outcomes. Although research indicates that stress and depression are associated with poorer cancer survival,1 controversy surrounds the interpretation that psychosocial and biologic factors indeed may contribute interdependently to disease processes.2

Physiologic Effects of Stress

Stress generally occurs when an event or situation (stressor) places demands on an individual or tests coping abilities. Normal physiologic responses evolved evolutionarily to help organisms deal with threats. For example, to escape from a predatory threat, automatic physiologic responses include increased heart rate, faster and shallower breathing, increased perspiration, and the shunting of blood to muscles.

Under such conditions, other body systems tend to decrease function. For example, digestion is decreased to enable the expenditure of additional energy on systems that will best help the body deal with the stressor. To counterbalance the sympathetic nervous system and hypothalamic-pituitary-adrenal response once the acute stressor is over, the parasympathetic system engages, decreasing heart rate, slowing breathing, and relaxing muscles, allowing return to the prestressor balanced state of function and resting under parasympathetic tone.

Stressors in life are many and varied, but typically they are characterized by an event that is challenging, harmful, induces fear, or represents loss. Although the acute physiologic reaction associated with the “fight or flight” response has been evolutionarily helpful for survival and is adaptive, when these situations occur frequently and the demands on the system exceed coping abilities, stress becomes chronic. Under these conditions, one lives in a constant sympathetic state, and excessive demands on the system ensue. These biobehavioral factors can result in maladaptive physiologic responses including prolonged increases in sympathetic nervous system and hypothalamic-pituitary-adrenal axis activity.3

The brain also responds in the “fight or flight” fashion and, in fact, may be viewed as the major orchestrator of the response. The brain usually shifts into a high-alert brain-wave activity state while the stressor is present and then shifts back to more relaxed activity once the stressor is gone (usually slower; parasympathetic tone). Under chronic stress, it becomes more difficult for the brain to switch between sympathetic and parasympathetic arousal, so that the brain and the rest of the body rarely have the opportunity to recover.

Over time, the body will struggle to recover after a stressful event, even if the stressor is no longer present. Unmanaged chronic stress can speed the aging process through telomere shortening,4 and increases the risk for heart disease,5 sleeping difficulties,6 digestive problems,7 and even depression.8 Moreover, chronic stress can also cause patients to forgo healthy eating and exercise habits that help prevent cancer and other disease.

Stress and the Tumor Microenvironment

The health-damaging effects of chronic stress are well documented in the medical literature, and research indicates that chronic stress affects almost every biologic system.9 With regard to cancer, there is little convincing evidence that chronic stress affects cancer initiation. However, there is extensive evidence that chronic stress can promote cancer growth and progression.10-12

The underlying mechanisms for such effects are complex and involve chronic activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis.13-15 Sustained elevations from these pathways (eg, norepinephrine, cortisol) can result in diverse effects including stimulation of cancer invasion, angiogenesis, inflammation, reduced anoikis, and even reduced efficacy of chemotherapeutic agents.16-18

The underlying signaling pathways19 offer opportunities for designing new therapeutic approaches to disrupting the effects of stress biology on cancer biology. These include both biobehavioral and pharmacologic approaches (eg, beta-blockers).

Screening and Treating Chronic Stress

According to the National Comprehensive Cancer Network (NCCN), distress is:

a multifactorial unpleasant emotional experience of a psychological (cognitive, behavioral, emotional), social, and/or spiritual nature that may interfere with the ability to cope effectively with cancer, its physical symptoms and its treatment. Distress extends along a continuum, ranging from common normal feelings of vulnerability, sadness, and fears to problems that can become disabling, such as depression, anxiety, panic, social isolation, and existential and spiritual crisis.20

The NCCN Clinical Practice Guidelines in Oncology suggest that all patients be screened with the single-item “distress thermometer.”20 The distress thermometer asks patients to rate their distress using a scale ranging from 0 (“no distress”) to 10 (“extreme distress”). Patients also indicate their source of distress by checking off issues listed on a 34-item problem list. The list includes practical problems, family problems, emotional problems, spiritual/religious concerns, and physical problems.

While some distress is normal, it is not benign and must be addressed, as failure to do so may compromise health and quality-of-life outcomes. The NCCN recommends that those scoring ≥ 4 on the distress thermometer be referred to a mental health-care professional for further evaluation.

A number of different approaches can be used to manage distress in patients with cancer including behavioral, pharmacologic, or a combined approach. Cognitive-behavioral therapy, cognitive-behavioral stress management, and antidepressants or anxiety medications have all been found to help in treating anxiety and depression in cancer patients. In fact, a recent study of cognitive-behavioral stress management found that this technique led to decreases in inflammatory gene expression, with previous studies reporting improvements in mood, quality of life, and ability to find meaning in the illness experience, among other benefits.21,22

Although these approaches will be useful for some patients, many seek strategies to manage their distress that are outside the conventional areas of psychiatry and clinical psychology. Mind-body practices constitute one method of increasing brain flexibility to help maintain a healthy balance between sympathetic and parasympathetic arousal.

Mind-Body Practices

A key ingredient to managing chronic stress is to have patients engage in behaviors that decrease sympathetic and increase parasympathetic arousal—that is, clinicians should encourage patients to learn how to relax in stressful situations. Mind-body practices are one way to achieve this goal. Research shows that mind-body practices have a positive effect on all body systems, improving quality of life, reversing the harmful effects of stress, and creating fundamental changes in brain function.23-31

Mind-body practices to help manage stress include meditation, various forms of yoga, and practices such as tai chi and qigong. These practices may be understood as movement-based meditations. They affect neurotransmitters (eg, glutamate, GABA) and neuromodulators (eg, dopamine, serotonin, epinephrine), which are essential in maintaining a healthy balance between sympathetic and parasympathetic arousal, thereby helping to manage the stress response.32

Mind-body practices can help decrease chronic stress by bringing balance to the body and, ultimately, to patients’ lives.33 It is clear from multiple studies of mind-body interventions that it is important for patients to participate in some kind of program and/or to include a mind-body practice in their lives to manage stress and improve their quality of life. There are many types of mind-body programs that can be useful.

Meditation

Meditation has been described as “a wakeful hypometabolic physiologic state”34 in which the practitioner is extremely relaxed yet alert and focused. Although meditation methods can vary, most types of meditation share common features such as focused, controlled regulation of breathing and control over thoughts and feelings, whether the goal is to inhibit and/or acknowledge and release external thoughts and feelings.

Given the continuous attention-based processes involved in initiating and maintaining a meditative state, meditation has been proposed to be an attentional training exercise. Among other benefits, it helps bring awareness to the relationship between the mind and body, acknowledging the constant dialogue and bidirectional effect that the mind and body have on one another.

Meditation and meditative movement practices may help the brain invoke the parasympathetic response to chronic stress, to thereby balance the sympathetic strain. Most brain activity is electrical. Electrical rhythms are classified into groups according to the speed with which they relay information. Delta is the slowest brainwave and is predominant in sleep states; theta can equal a state similar to daydreaming; alpha is associated with relaxation; and beta is associated with attention and intellectual activity.

Brain research demonstrates that the mechanisms of meditation induce electrical frequencies that are thought to be, in part, the switch between hyperarousal and relaxation. For example, under meditation conditions, the brain often shows changes in activity in the alpha wave.35,36 Alpha triggers mental relaxation and is an idle rhythm of the brain as it waits for cues from other parts of the body and the environment. This and other brain electrical rhythms affect neuromodulators, such as dopamine and serotonin, which are also essential to maintain a healthy balance between sympathetic and parasympathetic arousal and to manage the stress response.

Mind-body practices, therefore, help regulate relaxation in the body through a bidirectional conversation between electrical and chemical messages in the brain and the translation of those messages throughout the body. A feedback loop follows, where the brain receives signals from the rest of the body about the current state of arousal. As meditation with awareness continues, the body continues to relax and improve the balance across functional systems. Consequently, these practices can help regulate chronic stress, facilitating the integration of the mind and body.

Overall Health Effects

Mind-body research indicates that these practices have an effect on all physiologic systems, such as immune and hormone systems, neurotransmitters (neuromodulators) and even gene expression, thus improving aspects of quality of life, and creating fundamentally beneficial changes in the way the brain works. The neurologic effect of mind-body practices demonstrates the brain’s profound ability to change itself through experience.

This new frontier of medicine reveals the importance of managing chronic stress and underscores how influential behavior is on how the brain works and on overall health and well-being. Mind-body practices are one such healthy behavior with which to achieve balance and teach the brain flexibility.

Patients often ask which mind-body program is the best for reducing stress and improving quality of life. The answer is the one they will do every day and make a part of their life. Mind-body techniques are many and varied. Encourage your patients to find a mind-body approach that works for them and to practice it daily. ■

Dr. Cohen is Professor in the Departments of General Oncology and Behavioral Science, and Director of the Integrative Medicine Program, and Dr. Sood is Professor in the Department of Gynecologic Oncology and Reproductive Medicine, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston. Dr. Prinsloo is a Population Sciences Fellow in the Integrative Medicine Program and Dr. Chaoul is Assistant Professor in the Department of General Oncology and Director of Education in the Integrative Medicine Program at The University of Texas MD Anderson Cancer Center, Houston.

Disclosure: Drs. Cohen, Sood, Prinsloo, and Chaoul reported no potential conflicts of interest.

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Learn More About The University of Texas MD Anderson Cancer Center’s Integrative Medicine Program at www.mdanderson.org/integrativemed

Guest Editor

Integrative Oncology is guest edited by Barrie R. Cassileth, MS, PhD, Chief of the Integrative Medicine Service and Laurance S. Rockefeller Chair in Integrative Medicine at Memorial Sloan-Kettering Cancer Center, New York.

The Integrative Medicine Service at Memorial Sloan-Kettering Cancer Center developed and maintains a free website—About Herbs (www.mskcc.org/aboutherbs)—that provides objective and unbiased information about herbs, vitamins, minerals, and other dietary supplements, and unproved anticancer treatments. Each of the 265 and growing number of entries offer health-care professional and patient versions, and entries are regularly updated with the latest research findings.

In addition, the About Herbs app, Memorial Sloan-Kettering Cancer Center’s very first mobile application, was launched last fall. The app is compatible with iPad, iPhone, and iPod Touch devices, and can be downloaded at http://itunes.apple.com/us/app/about-herbs/id554267162?mt=8.

Compiled by Barrie R. Cassileth, PhD, and Jyothi Gubili, MS, Memorial Sloan-Kettering Cancer Center. The About Herbs website is managed by K. Simon Yeung, PharmD, MBA, Lac, Memorial Sloan-Kettering Cancer Center.



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