One of the key pillars of  integrative oncology is stress reduction.  

The majority of us intuitively recognize the link between stress and the immune system. How many times in your life have you come down with a cold or other viral infection shortly after periods of high-stress? Now, imagine what your body goes through when exposed to stress over years. Substantial evidence suggests that exposure to long periods of stress increases rates of cancer development and growth. How is this possible, you ask?

Stress and cancer development:

Scientists (psychoneuroimmunologists), believe that this is the end result of our chronically stressed-out brains sending stimulatory signals to our adrenal glands to produce stress hormones (like cortisol and epinephrine.) Long-term exposure of our cells to these hormones causes:

  • Stress hormones increase the production of free radicals–>DNA damage and impaired immune function
  • Stress hormones increase inflammation through the production of inflammatory proteins (cytokines) –>impair immune function and promote cancer growth
  • Stress hormones directly impair immune cell function
  • Stress hormones reduce the ability of abnormal cells to undergo apoptosis (cell death) and DNA repair, important self-regulating anticancer mechanisms
  • Stress hormones stimulate the production of IGF-1 (insulin-like growth factor-1), VEGF (vascular endothelial growth factor) and other growth factors that can promote tumor cell growth

The immune surveillance theory (or, immunosurveillance theory) postulates that at any one time within an individual, there are numerous cells (precancerous and malignant) that have the potential to become a tumor if not detected and destroyed by the immune system. Fortunately, in the presence of a healthy immune system, immune cells (i.e. white blood cells, natural killer cells, macrophages) protect us by detecting and eliminate these precancerous and cancer cells as soon as they identified.  Our immune system is also constantly protecting us from viruses that can cause cancer (i.e. Epstein-Barr virus, human papilloma virus, hepatitis C virus, hepatitis B virus, human herpes virus 8 and human T-cell leukemia virus.) If our immune system is weakened or suppressed, precancerous and cancer cells and cancer-causing viruses are able to wreak havoc and eventually lead to the development of uncontrolled cancer cell growth.

Severe stress, such as occurs in individuals diagnosed with post-traumatic stress disorder (PTSD), appears to lead to permanent changes to genes (DNA) that control immune function. In a study (published in May 2010, in the Proceedings of the National Academy of Sciences) investigators have discovered that individuals with PTSD have 6-7 times as many changes to genes that control immune function compared to individuals without PTSD. Although the precise mechanism(s) to explain how these genetic changes take place is(are) not yet known, we now have data that show that PTSD can permanently change one’s DNA, reducing the function of their immune system.

Did you know that having a diagnosis of cancer can lead to post-traumatic stress disorder or cause many of the same symptoms that are experienced by those with this condition? There are many individuals who develop powerful emotional and psychological responses to their cancer diagnosis, symptoms and treatment that they can develop severe stress syndromes. In a study (published in May 2010, in Pediatrics) investigators found that in a population of over 6,500 adults, who were survivors of childhood cancers, there was high-percentage who reported signs and symptoms consistent with a diagnosis of post-traumatic stress disorder (PTSD). The authors compared the cancer survivors to those of their unaffected siblings, and noted that the survivors had a 4-fold higher risk of having PTSD.

Further complicating this picture, it is well-recognized that stress is associated with various high-risk behaviors that may increase the risk of developing cancer (i.e. smoking and excessive alcohol use, poor diet, lack of exercise, obesity, etc.) Sleep is commonly affected as a consequence of stress, and emerging data correlate disturbed circadian rhythms with increased incidence of certain cancers. Altered circadian (sleep-wake cycle) rhythms have been shown to affect the neurohormal axis, and thus modify the regulation of the immune system. The pineal hormone melatonin has been linked to numerous mechanisms attributed to immune enhancement (i.e. increased T and B cell immunity, increased monocyte activity, increased NK cell activity, increased secretion of cytokines), reduction of oxidative stress (free radicals), tumor cell apoptosis (cell death/suicide) and reduction of blood vessel growth in tumors.

Stress and Cancer Progression:

Once a tumor has developed, stress may modulate neuroendocrine pathways and affect numerous mechanisms that potentially lead to the progression of cancer:

  • Stress hormone stimulation of beta-adrenergic receptors (present on all cells) increases tumor growth rates
  • Stress hormones increase tumor cell invasiveness and metastatic activity
  • Stress hormones increase tumor blood vessel growth
  • Stress hormones suppress natural killer (NK) cell activity (immune suppression)
  • Stress hormones reduce the cancer-killing effects of chemotherapy on tumor cell apoptosis (cell death/suicide)

Stress may be present from diagnosis to the survivorship period, and can be associated with behavioral comorbidities and diminished quality of life (i.e. depression, fatigue, sleep disturbances, and cognitive dysfunction.) Medical complications or side effects of cancer and treatment can further exacerbate these symptoms.

Multiple studies demonstrate that chronic stress increases the rate of tumor metastases in animals with cancer. For example, norepinephrine (stress hormone) has been shown to increase the migration of breast, prostate, and colon carcinoma cells (in-vitro) and increase the incidence of prostate carcinoma lymph node metastases (in-vivo.) This phenomenon seems likely to be related to the chronic stimulation of beta-adrenergic receptors (stress hormone receptor):

  • In a study (published in Cancer Research, September 2010), investigators from UCLA examined the effects of chronic stress in mice injected with breast cancer cells. The mice were subjected to a chronic stress model by being confined to a small cage for 2-hours each day for 20-days. During this time, they underwent injection of fluorescent-labeled breast cancer cells and then observed for metastatic spread. They compared the results to a control group of mice that were not subjected to chronic stress. The results were significantly different. The stressed mice had a 30-fold increase in the development of metastases compared to the non-stressed mice. The authors found, in the stressed mice, that cells in their immune system (i.e. macrophages) were genetically altered by the activity of stress hormones in such a way that increased the ability of the injected cancer cells to gain access to the blood system and thereby spread around the body.
  • Interestingly, the researchers also tested the effects of a stress hormone blocking medication (“beta-blocker”, propranolol) on the stressed mice. What they found was incredible…propronalol completely blocked the effects of stress hormones on causing the rapid progression of cancer metastases! As propranolol is an inexpensive and widely available blood pressure medication, the authors have suggested that it may have a future role in helping to reduce the risk of cancer progression.

Stress is often associated with sleeping disturbances. Increasingly, data suggest a link between disruptions in the circadian (sleep-wake) rhythm and cancer:

  • direct effects of altered hormone levels on tumor cells
  • effects on tumor versus host metabolism
  • neuroimmune effects resulting in cell mediated immune suppression
  • increase cortisol release and expression of pro-inflammatory cytokines (i.e. IL-6, tumor growth factor-alpha), which can stimulate tumor development and progression
By reducing stress, sleep disturbances should improve and these cancer promoting effects will be diminished. (Read more about this on my blog entry on this subject.)

Why is stress reduction so important?

It is a well-known fact that chronic stress negatively impacts the health of individuals with a variety of medical conditions (cardiovascular disease, diabetes, obesity, chronic pain, autoimmune diseases, depression, inflammatory bowel syndromes/disorders, etc.) Helping individuals with these conditions learn how to cope with and reduce stress has been demonstrated in numerous studies to not only reverse the physiologic effects of stress hormone exposure, but also significantly improve disease, overall health outcomes and quality of life. Okay, but what about the impact of stress reduction on cancer?

Stress reduction may improve cancer survival rates:

The effects of long-term exposure of stress hormones on our cells has not been definitely linked to the development or progression of cancer, but the evidence supporting this potential association is very compelling. It seems highly unlikely that chronic stress exacerbates nearly every other disease except for cancer.

An important meta-analysis (published in 1998, in Nature Reviews Clinical Oncology), of 165 studies on the topic of stress and cancer statistics (incidence & outcomes), reported that stress was associated with higher cancer incidence in initially healthy populations (6-21% higher) and higher cancer mortality (29-133% higher). The following study is one of the strongest pieces of evidence ever reported on the positive impact of stress reduction on cancer progression and recurrence:

  • In a study (published in June 2010, in Clinical Cancer Research), investigators update the results of a fascinating experiment in which 227 breast cancer patients were randomly assigned to two groups: group 1 (received psychological interventions such as relaxation training and advice on minimizing stress in 39 therapy hours, over 12 months), group 2 (received no psychological interventions). The patients have been followed for over 11 years since their initial enrollment. Patients were reassessed every four months during year one, every six months during years two to five, and annually thereafter. In their initial publication, the authors previously reported that patients in the intervention group had a 45% reduced risk of breast cancer recurrence, improvements in multiple immune function measurements, and improvements in various quality of life outcomes.
  • In this paper, the authors analyzed the patients who recurred in both groups. Incredibly, they found that those in the intervention group had a 59% reduced risk of death from breast cancer!!

The results of this important study suggest that a relatively short and inexpensive psychosocial stress reduction program may be effective in improving the survival of breast cancer patients.

The authors hypothesize that the mechanism for this improvement in survival and reduction in recurrence is due to the positive effects of stress reduction on the immune system.

To satisfy the skeptics out there, I want to emphasize (dare I say ‘stress’) the point that the direct association between chronic stress, the immune system and cancer has not been definitively established, but increasingly the evidence seems to support this.

While the concept of stress is universal and readily understood, it is often a challenge to operationalize it for research.  Perhaps one of the reasons for why linkages between cancer and psychological stress is not well-defined is due to the lack of clear understanding on what constitutes stress, and how stress is measured and defined. Stress is a not a distinct state of mind, but is in fact a combination of various psychological components (i.e. depression, anxiety, frustration, fear, hopelessness, etc.) resulting from exposure to adversity, cognitive appraisal, behavioral characteristics and coping style, personality, social support, and emotional responses. Each of these components may be activated by different emotional or physical experiences and can involve different neural pathways, ultimately leading to complex downstream physiological effects.

Stress reduction improves quality of life:

Regardless of whether stress reduction techniques are able to improve cancer outcomes, there is no doubt that they can greatly improve quality of life. Stress reduction techniques can involve any of variety of effective options, such as: massage therapy, meditation, guided imagery, yoga, cognitive based therapies, prayer, walking on the beach, and many others. Here are three studies looking at just one of these stress reducing modalities, yoga:

  • recent study reported that breast cancer survivors who practiced yoga for 3-months had a significant reduction in cancer related fatigue and improved vigor. This reduction in fatigue is thought to be due to yoga’s effects on the immune and neuroendocrine systems (likely through increased physical activity and stress reduction).
  • A short, 4-week yoga course has also been reported to improve sleep quality and fatigue after cancer treatment.
  • An 8-week yoga course was reported to reduce salivary cortisol (stress hormone) levels, improve emotional well-being and reduce fatigue after cancer treatment.

Useful References:

Great technique for relaxing: “The 4-7-8 (or Relaxing Breath) Exercise”

I highly recommend this relaxation technique as a very simple and effective way to get you into a relaxed state quickly. You can learn the “relaxing breath” in a short amount of time and it is very easy to do. This can be done before going to bed, before going to the doctors office (if that makes you nervous) or in any stressful situation.

Instructions (from DrWeil.Com)

“Place the tip of your tongue against the ridge of tissue just behind your upper front teeth, and keep it there through the entire exercise. You will be exhaling through your mouth around your tongue; try pursing your lips slightly if this seems awkward.”

    • Exhale completely through your mouth, making a whoosh sound.
    • Close your mouth and inhale quietly through your nose to a mental count of four.
    • Hold your breath for a count of seven.
    • Exhale completely through your mouth, making a whoosh sound to a count of eight.
    • This is one breath. Now inhale again and repeat the cycle three more times for a total of four breaths.

The figure (below) illustrates some of the mechanisms that have linked the development and progression of cancer with stress

(“The Influence On Bio-Behavioural Factors On Tumour Biology: Pathways & Mechanisms”, Antoni, M.H., et. al., Nature Reviews, March 2006)

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–Dame Cicely Saunders Hospice is a philosophy of coordinated care for patients and their loved ones. Hospice is not a place, but a concept of care [...read more...]

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Nutrition consultations are an integral component of cancer care

It is fairly common for patients undergoing chemotherapy and/or radiation therapy to develop side effects that can lead to weight loss, dehydration, diarrhea or constipation. Diminished appetite and taste changes (i.e. certain foods may lose their taste or become unpalatable) can occur during these treatments, making it difficult for some patients to maintain their weight. Swallowing can sometimes become difficult for patients who are receiving certain chemotherapy drugs or when undergoing radiation therapy to treat various cancers in the head, neck or chest.  Occasionally, these treatments can temporarily irritate mucous membranes, causing pain. Oral secretions can become thick and dry, [...read more...]

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Massage is an excellent therapy to help relieve pain, anxiety and stress for anyone with a diagnosis of cancer

Numerous, high-quality studies have been published over the last decade demonstrating the effectiveness of massage in reducing pain, stress and anxiety in individuals with cancer. These studies have included patients of all ages (infants to elderly), timeframes (before, during and after cancer treatment) and stages of cancer (early, advanced, in remission.) Regardless of the massage technique (Swedish, light touch, etc.) and protocol (duration and schedule), the vast majority of individuals derive significant quality of life benefits. Researchers have postulated that massage works through multiple mechanisms: increased blood and lymphatic movement, stimulates release of natural pain and stress reducing molecules (endogenous [...read more...]

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Discuss ALL your medications and supplements with your cancer care team: Potentially serious interactions are common among cancer patients

Studies indicate that one-third of cancer patients take combinations of medications (both prescribed and non-prescription/over-the-counter drugs) that place them at risk of potentially dangerous interactions. (Read More Here) This number may actually be far greater after accounting for the widespread use of  dietary supplements, including high-dose vitamins and various botanical/herbal therapies. To make matters even more confusing, studies have demonstrated potentially serious interactions that can occur when consuming certain foods (i.e. grapefruit) while taking medications that are metabolized by the liver. Drug-drug interactions, drug-supplement interactions and drug-food interactions can range from minor interactions that have little to no noticeable effects [...read more...]

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Anxiety & stress can be reduced with a simple, 5-minute acupuncture treatment

A study published, in March 2010 (in Acupuncture in Medicine/British Medical Journal) reports a 50% reduction in measured anxiety scores following a single, 5-minute acupuncture treatment.  All enrolled patients had a history of severe anxiety prior to undergoing dental procedures. The patients received their acupuncture treatment 5-minutes prior to undergoing a dental procedure. It is not uncommon for cancer patients to experience significant anxiety surrounding their conventional cancer treatment (i.e. chemotherapy, radiation therapy, surgery, etc.) Although this study was not conducted with cancer patients, it is certainly compelling to consider using a similar, 5-minute acupuncture treatment in the oncology setting. (Read More [...read more...]

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Greater than 50% of breast cancer patients either discontinue or are non-adherent to hormonal therapy regimens

In a study published, in June 2010 (in the Journal of Clinical Oncology) investigators have found that over 50% of breast cancer patients, who have been prescribed hormonal therapy medications (“aromatase inhibitors” or “Tamoxifen”) for preventing recurrence of breast cancer, either prematurely discontinue or do not take their medication as prescribed (“non-adherence” was defined in this study as, taking <80% of the prescribed pills.) All patients in this study (8,769 patients) had “estrogen positive”, invasive breast cancers (stages 1-3) and were therefore recommended to take hormonal therapy for a total of 5-years.  Previous studies have demonstrated that patients who take less than 5-years [...read more...]

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Millions of cancer survivors suffer from lymphedema- Early diagnosis and treatment is essential

Did you know that as many as 3-5 million individuals suffer from lymphedema in the United States, and the majority of whom develop this condition as a result of cancer treatment (i.e. surgery and/or radiation therapy to the lymph nodes within the neck, armpit, pelvis and groin)?  In the United States, the most common cause of lymphedema is due to breast cancer treatment, but it can result from the treatment of cervical, endometrial, vulvar, head and neck, and prostate cancers, as well as sarcomas and melanoma. The risks of developing lymphedema depend on multiple factors, including the extent of treatment to the [...read more...]

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Vitamin D decreases the risk and duration of many viral infections, including the flu and colds

In a study published in June 2010 (in the journal PloS ONE), researchers report that in a group of patients that they followed (198 healthy adults, during the fall and winter 2009-2010) the one’s who had higher vitamin D (25-hydroxyvitamin D) levels (>/=38ng/ml) developed significantly fewer viral infections over the study period than those who had lower levels of vitamin D (17% versus 45%). Additionally, those with the higher levels of vitamin D also experienced significantly fewer days of illness (i.e. in those with influenza: 2 days of illness versus 6 days of illness, for those with the higher vitamin D [...read more...]

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Are you on Tamoxifen? A simple test can tell you if you are at a high risk of blood clots

In a study, published in June 2010 (in the Journal of the National Cancer Institute) investigators reported that breast cancer patients who were on Tamoxifen (a hormonal drug that blocks the estrogen receptors on tumor cells) and had a unique gene mutation (called “Factor 5 Leiden” or “FVL”) were 5-times more likely to develop blood clots or thromboembolic events (i.e. pulmonary emobolism) than patients without this genetic mutation. Tamoxifen has been previously reported to increase a patients risk of developing a thromboembolic event (TE) by 2-times compared to those not on Tamoxifen. This is widely known in oncology and is [...read more...]

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Cancer survivors and patients should get at least 150 minutes of exercise per week

The American College of Sports Medicine now recommends that individuals with cancer (either undergoing treatment or survivors) should do at least 150 minutes per week of moderate-intensity aerobic activity. This is based on a new roundtable statement, issued by the group at their 2010 Annual Meeting. This recommendation is supported by numerous studies indicating the benefits of exercise in those individuals actively undergoing treatment for cancer and/or after treatment (i.e. reduced fatigue, improved sleep function, improved overall quality of life, improved muscle strength and flexibility, improved cardiovascular performance, improves immune function, reduces stress, reduced risk of cancer recurrence, etc.) Exercise [...read more...]

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Integrative Oncology Essentials: A Patients' Guide To Cancer Care And Prevention (Free Download!!)

I have written a guide (Integrative Oncology Essentials: A Patients’ Guide To Cancer Care And Cancer Prevention) for my patients that covers many of the important topics I address in my integrative oncology lectures and consultations. I am pleased to offer this guide, as a free download (CLICK HERE: IOE Guide_V3). I really hope that the information is helpful to you, your loved ones and anyone who is interested in learning more about using integrative oncology approaches to cancer prevention and cancer care. I would be grateful to hear your comments and suggestions on how to improve future versions of this [...read more...]

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Yoga significantly reduces fatigue and improves sleep quality after cancer treatment

In a study (abstract published online in May 2010, Journal of Clinical Oncology; to be presented on June 5th, at the American Society of Clinical Oncology 2010 annual meeting, in Chicago) investigators, from the University of Rochester Medical Center, report the results of a randomized controlled trial of a short course of yoga compared to a control (usual care- no yoga) for patients who have completed treatment for cancer. The study was designed to analyze the potential effects of yoga on cancer treatment-related fatigue and on sleep quality, both of which are frequent problems in patients during and after treatment [...read more...]

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Acupuncture reduces neck/shoulder pain and dry mouth after treatment for head & neck cancers

In a study (published in May 2010, in the Journal of Clinical Oncology) investigators from the Memorial Sloan-Kettering Cancer Center studied the potential benefits of acupuncture in patients with cancers of the head & neck who had undergone lymph node surgery (neck dissection.)  Neck and shoulder pain is a common symptom (occuring 30-70% of the time) in patients who have undergone a neck dissection.  Because acupuncture has been shown in multiple studies to improve neck and shoulder pain from non-surgical causes, the study authors designed a study to examine if it could be used in treating post-surgical pain in these patients. [...read more...]

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Social interaction (even over the phone) reduces the body's response to stress

In a study (published in May 2010, in the Proceedings of the Royal Society B.) investigators have demonstrated that social interaction (over the telephone) after a stressful event significantly decreases amount of stress hormones (cortisol) produced.  In this study, a group of 7-12 year-old girls were divided into 3 groups after being exposed to a stressful event (unanticipated speaking in front of a group of strangers and being asked to answer difficult math questions.) The first group was immediately reunited with their mothers, for 15-minutes, for comfort and support (in person.) Afterwards, they watched an emotion-neutral movie, for 60-minutes. The second group spoke to their mothers, [...read more...]

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What is Integrative Oncology? I created diagrams to illustrate the holism and complexity of this fascinating subject.

Visit the Integrative Oncology-Essentials Website to learn more about the core principles to help prevent cancer development and cancer recurrence. I developed diagrams (CLICK HERE to see in FULL-SIZE) to help explain to my patients the core principles of integrative oncology. It shows the process of how healthy, normal cells transform into cancer cells. They demonstrate how lifestyle and behaviors can influence this process and can be used to decrease one’s risk of cancer development and progression. Importantly, the diagrams show how cancer and its’ treatment can lead to the development and exacerbation of other medical problems (Did you know that most [...read more...]

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Post-traumatic stress disorder in cancer survivors

In a study (published in May 2010, in Pediatrics) investigators found that in a population of over 6,500 adults, who were survivors of childhood cancers, there was high percentage who reported signs and symptoms consistent with a diagnosis of post-traumatic stress disorder (PTSD). The authors compared the cancer survivors to those of their unaffected siblings, and noted that the survivors had a 4-fold higher risk of having PTSD. (Read More Here) This study is important for integrative oncologists as it clearly demonstrates the severe psychoemotional consequences that can occur following the diagnosis and treatment of cancer. Although this study evaluated only [...read more...]

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Smoking increases the risk in breast cancer survivors for developing a new breast cancer

In a study (presented at the May 2010 meeting of the American Radium Society) investigators report the results of their analysis of 796 breast cancer survivors who smoked after their treatment for breast cancer. All of these patients received lumpectomy (with or without radiation therapy). The authors found that the rate of developing a new breast cancer (in either the same or opposite breast) and any new cancer was significantly higher in this group of smokers compared to a non-smoking group of breast cancer survivors. (Read More Here) Integrative oncology counseling provides numerous recommendations for cancer survivors that may help to reduce [...read more...]

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