Lifestyle Interventions Enhance Quality of Life and Reduce Recurrence Risk Among Cancer Survivors

A review of the literature

By Lise Alschuler, ND, FABNO, Matt Mumber, MD, and Karolyn A. Gazella

Printer Friendly PagePrinter Friendly Page

Abstract

As of January 1, 2016, there were 15.5 million cancer survivors in the United States and, according to the American Cancer Society, this number is projected to increase to 20 million by 2026.1 In recognition of the unique health needs of this growing population, the American College of Surgeons Commission on Cancer (CoC) has mandated that cancer centers provide survivors with a Survivorship Care Plan (SCP).2 Additionally, in 2013, the National Comprehensive Cancer Network (NCCN) also developed cancer survivorship guidelines. According to the CoC mandate, an SCP must provide a treatment overview, describe recommended follow-up care, and provide information about lifestyle-based risk reduction. This review provides scientific substantiation regarding key lifestyle intervention strategies that both help cancer centers meet, and in fact, exceed the mandate, and help cancer survivors heal from treatment, reduce their risk of cancer recurrence, and enhance overall wellness. 

Significance of Survivorship Care Plan Mandate

In 2005, the Institute of Medicine (IOM) issued a report to address the health needs of cancer survivors.3 One of the recommendations in this report was that after completing active treatment (not including ongoing endocrine treatment), patients be provided with an SCP that includes a comprehensive care summary and follow-up plan. The American College of Surgeons CoC adopted the IOM recommendations and in 2012 issued an SCP mandate as a standard for accreditation. This mandate requires accredited programs to implement treatment summaries and SCPs in order to help improve communication, quality, and coordination of care for cancer survivors. The original implementation timeline for 2015 was subsequently extended with a phased in-approach for providing all eligible patients with an SCP, recommending that 25% be provided with an SCP by January 2017, 50% by January 2018, and 75% by January 2019, with the ultimate goal of providing an SCP for all eligible patients.4 Given that more than 1,500 CoC-accredited facilities diagnose and/or treat 80% of newly diagnosed cancer patients each year,5 the impact of this mandate on survivorship cannot be understated. 
 
The NCCN guidelines, which are the standard of care guidelines for much of oncology, recommend ongoing assessment of survivors for late effects of treatment and long-term psychological and physical issues. In addition, the NCCN guidelines address preventive care, based on lifestyle practices. These guidelines also emphasize the importance of managing the health of people diagnosed with cancer after active conventional treatment ends. 
 
Despite the CoC mandate as well as the NCCN survivorship guidelines, cancer centers are struggling to meet the needs of their survivors.6 There are logistical and resource challenges with the implementation of SCPs.7 Additionally, providing meaningful lifestyle-based risk reduction and health optimization strategies is outside of their typical provision of care. While the intent of the CoC mandate and the NCCN guidelines is to meet the needs of cancer survivors, the impact of the mandate and guidelines on these needs is yet to be realized. 

Special Needs of Cancer Survivors

The National Cancer Institute (NCI) defines survivorship as beginning at the time of diagnosis. The IOM defines survivorship as beginning after completion of treatment for the initial cancer. For the purpose of this review, we adopt the NCI definition (survivorship begins after initial diagnosis), but our emphasis is on the time period after active treatment ends. Survivors often describe the time period following active oncology treatment as extremely challenging. Their physical, emotional, and social needs are high. This is the impetus for the development of survivorship care. Unfortunately, at the same time, they also lose their regular touchpoints with their care providers as well as access to the ancillary support services offered by cancer centers. This loss of support comes at a critical time. 
 
A variety of studies have confirmed that cancer survivors have special health needs that relate to their diagnosis and/or long-term treatment side effects. In addition, because many survivors are often at increased risk of disease recurrence, tertiary prevention remains a key health objective. A variety of surveys indicate that anywhere from 30% to 60% of survivors feel their special health needs are not being met.8,9 The unmet needs of cancer survivors can be physical, financial, relational, and/or psychological.10 In the physical realm, 80% of patients treated with chemotherapy and up to 90% of those treated with radiation experience fatigue.11 Sleep disturbances affect between 30% and 75% of people diagnosed with cancer.12 Up to 75% of people diagnosed with cancer experience cognitive impairment during or after treatment, and in 35% of those cases it can persist for months or even years after treatment is completed.13,14 From a psychological standpoint, up to 70% of survivors report “clinically significant levels” of fear of recurrence and this is true even when actual recurrence risk is low.15
 
These special health needs fueled the development of the CoC survivorship mandate. In spirit, the CoC mandate promotes lifestyle-based risk-reduction and health optimization strategies. However, in practice, the requirements of the mandate are met if the survivor receives a general statement that emphasizes the importance of a healthy diet, consistent exercise, smoking cessation, and reduced alcohol consumption. While this is a step in the right direction, preliminary data indicates that the SCPs are causing more anxiety than comfort. A 2015 randomized trial showed that SCPs increased patient concerns and symptoms associated with their cancer and had a negative emotional impact.16 The authors speculate that one reason for this may be that the SCP focuses on the treatment summary and follow-up care recommendations with only cursory guidance provided on proactive risk reduction and health optimization. The anxiety experienced by survivors upon receiving the SCPs may be the result of inadequate emphasis on specific, individualized direction regarding lifestyle strategies that survivors can implement to recover from treatment and reduce the risk of recurrence. Despite the intention of the SCP, without empowerment in the area of lifestyle strategies, survivors have increased anxiety and may feel overwhelmed, which negatively impacts quality of life and potentially recurrence risk.
 
To help survivors recover following treatment and reduce the risk of recurrence, more emphasis should be placed on strategies associated with key lifestyle areas that can make the most impact.17 The lifestyle areas focused on in this paper include diet, exercise, environmental toxin exposure, stress management, and psychosocial wellness. Given that these areas fall solidly within the expertise of the integrative practitioner, directing cancer survivors into the care of integrative practitioners represents an ideal clinical path. In addition, there is a need for expanded lifestyle-based practitioners in cancer centers and/or self-directed, survivorship lifestyle programs that emphasize these areas of intervention. 

Diet

A Mediterranean whole foods, unprocessed diet has scientific substantiation when it comes to reducing cancer risk and improving overall health. The Mediterranean diet has been shown to reduce the risk of a variety of cancers including gastrointestinal,18 prostate,19 breast,20 and others.21 Health-promoting characteristics of the Mediterranean diet include the following:
  • Increased consumption of fruits and vegetables
  • Healthy fats in the form of olive oil, nuts and fish
  • High-fiber whole grains
  • Limited consumption of meat, cheese, and sweets 
Increased fruit and vegetable consumption is inversely associated with all-cause mortality including cancer.22,23 Intake of healthy fats is another area where scientific validation is strong. High intake of omega-3 essential fatty acids has been shown to reduce cytokine production and inflammation, key risk factors for the development of most cancers.24 Essential fats such as eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) have also been shown to activate macrophages and T-cells, as well as increase other aspects of immunity as they relate to cancer development and progression.25,26
 
In addition to cancer prevention, the NCI and many other prestigious organizations recognize that healthy eating habits can also help reduce treatment side effects, enhance recovery, and reduce risk of recurrence and death from cancer.16 A Mediterranean diet can help cancer survivors overcome some of the side effects associated with oncology treatment.27 While there are no studies demonstrating efficacy of the Mediterranean diet as protection against neurologic changes after treatments such as chemotherapy, or radiation-induced late neuropsychological changes, the anti-inflammatory cognitive effects of the diet indicate it may be protective among survivors. The cognitive benefits of a Mediterranean style diet have been established in other populations. A 2015 randomized trial demonstrated that the Mediterranean diet reduced the risk of cognitive decline in healthy older individuals without cancer.28 The Mediterranean diet has also been shown to reduce the risk of depression, which is something that a large number of survivors experience upon diagnosis and/or after treatment.29

Exercise

The myriad health benefits of exercise are undisputed. Specific to cancer survivorship, a significant amount of data indicates that exercise reduces side effects of chemotherapy and radiation, improves overall wellness and quality of life, and reduces risk of recurrence.30 Exercise has been shown to reduce side effects, including cognitive impairment, sleep disturbances, depression, pain, anxiety, and fatigue.31
 
Not that long ago, oncologists discouraged patients from exercising during treatment because they believed exercise enhanced fatigue. Today, it is well-known that exercise is one of the best ways to counteract cancer-related fatigue (CRF). The NCCN and other organizations recommend moderate exercise during treatment, stating that “those who exercised regularly had 40% to 50% less fatigue, the primary complaint during treatment.”32 A 2008 published study featuring older people with cancer who were experiencing fatigue concluded that “exercise programs continue to be the most popular and widely studied nonpharmacologic intervention for CRF.”33 In a 2009 review, 8 of the 10 studies evaluated demonstrated that exercise resulted in less fatigue among cancer survivors than the control groups.34 Presently the American Cancer Society recommends that to help reduce risk of cancer, adults should “get at least 150 minutes of moderate intensity or 75 minutes of vigorous intensity activity each week (or a combination of these), preferably spread throughout the week.”35 
 
In addition to addressing CRF and other treatment side effects such as sleep disturbances and depression,36 exercise has been shown to significantly improve overall quality of life in cancer survivors across many types of cancer including breast, prostate, and colon.37-39

Environmental Toxicity

It is now widely known that our environment contains carcinogenic chemicals. These chemicals can be found in the air (eg, car exhaust), water (eg, arsenic, chlorine, pharmaceuticals), body care products (eg, parabens, phthalates), and cleaning products (eg, triclosan, ammonia). A well-known pathway from environmental toxins to carcinogenesis is through endocrine disruption. The National Institute of Environmental Health Sciences (NIEHS) has identified endocrine disruption as an “important public health concern.”40
 
Chemicals that disrupt hormone function have the ability to modify hormonal signaling throughout the body. Normal functions associated with development, reproduction, and immunity are negatively affected. According to the NIEHS, these disruptions can contribute to obesity and diabetes, as well as progression of some diseases including cancer.39
 
While much of the data associated with toxic effects of endocrine disruptors is in vitro, emerging human data is confirming these results. Chemicals that disrupt hormone function by mimicking or displacing the body’s natural hormones can increase risk of certain cancers, especially hormone-dependent cancers of the breast and prostate.41,42
 
According to the NIEHS, chemicals that are confirmed endocrine disruptors in humans include the synthetic estrogen diethylstilbestrol (DES); dioxin and dioxin-like compounds found in auto exhaust and chemicals used to bleach paper; DDT and other pesticides; bisphenol A (BPA), found in a variety of products including plastic containers; and diethylhexyl phthalate (DEHP), used to make plastic softer.39 In addition to DEHP, all phthalates, which are industrial chemicals found in nearly any product that has synthetic fragrance, are known endocrine disruptors.43
 
According to a report by the Environmental Working Group, it’s not just exposure to one chemical carcinogen that is problematic; the combined subtle exposure to many chemical carcinogens over time increases risk of cancer.44 When cancer survivors reduce their overall combined exposure to chemical toxins in the air, water, body care, and cleaning products, they are likely reducing their risk of developing a new cancer or a cancer recurrence.45 By reducing toxic burden, survivors will also be supporting key pathways that can contribute to optimal health, including immune function and detoxification.

Stress Management

While the association between cancer development and chronic stress exposure is not as clear, the evidence demonstrating a direct link between chronic stress and cancer progression has been mounting over the past several decades. Strong evidence suggests that chronic stress impacts progression and metastasis via several significant pathways45 including angiogenesis,46 tumor cell adhesion47 and invasion.48
 
When key hormones such as cortisol, epinephrine, and norepinephrine are disrupted due to chronic stress, there are negative downstream effects on many tissues, organs, and systems in the body that can contribute to cancer cell mobilization and invasion. In vitro studies have found that elevated norepinephrine, at a level consistent with that found during the stress response, increases ovarian cancer cells’ invasiveness up to 198%.50 Additionally, stress-induced cortisol binding to the glucocorticoid receptor (GR) causes translocation of the GR to the cell nucleus and changes in the expression of apoptotic and DNA repair genes. Prolonged presence of cortisol during periods of stress leads to an increase in both the proliferative and antiapoptotic effects of the receptor, creating transformation-promoting intracellular conditions.49 Another pathway from stress to cancer is via the immune system. Distress measured by self-report is correlated with low natural killer (NK) cell cytotoxicity in tumor-infiltrating lymphocytes from human ovarian cancers.50 Low peripheral NK cell counts are prognostic for early breast cancer mortality, and reduced NK cell cytotoxicity is predictive of a poor clinical outcome in patients with breast carcinoma.51 Conversely, positive psychosocial factors such as social support , spiritual activities, and humor have each been associated with increased levels of NK cell cytotoxicity in patients with breast and ovarian cancer.52
 
It can be challenging in some cases to actually reduce overall stress; however, even if the amount of stress cannot be controlled, an individual’s stress response can be managed. Perhaps one of the most robust areas of research in terms of stress management are mindfulness techniques. Mindfulness is the act of bringing attention and awareness in each moment without judgment. While its roots come from Buddhist philosophy, it is also a part of many cognitive-based therapies. 
 
Mindfulness-based stress reduction (MSBR) techniques—primarily meditative in nature—have been shown to help many conditions that are associated with survivorship, including pain, anxiety, depression, and insomnia.53 Several studies have shown that MBSR programs improve symptoms of cancer treatment adverse effects and improve overall mood in cancer survivors.54
 
A 2016 review in the Annals of the New York Academy of Sciences concluded that mindfulness-based interventions are “particularly helpful in dealing with common experiences related to cancer diagnosis, treatment, and survivorship, including loss of control, uncertainty about the future, fears of recurrence, and a range of physical and psychological symptoms, including depression, anxiety, insomnia, and fatigue.”55
 
In addition to meditation, other mindfulness-based interventions can include biofeedback, cognitive behavioral therapy, diaphragmatic breathing, relaxation response, and guided imagery/visualization.56
 
Emerging research also indicates that nature provides healing benefits, specifically as they relate to stress management. A 2016 randomized trial demonstrated that images of nature provided a protective ability in lessening the stress response prior to being exposed to a stressor compared to images of an urban environment.57 A 2015 randomized trial using brain scans showed that walks in nature decreased mental rumination and enhanced mental health compared to walks along busy urban streets.58
 
Addressing sleep dysfunction is also a key strategy when managing stress in this patient population. Nearly 60% of survivors report that they developed insomnia or their sleep disturbances worsened following their cancer diagnosis.59 Stress is closely associated with sleep disorders and it is known that insomniacs have reduced capacity to cope with stress when compared to individuals who do not have insomnia.60
 
There are many ways to improve the individual stress response. While chronic stress can have deleterious outcomes including increased risk of cancer progression, according to the Society for Integrative Oncology clinical practice guidelines, techniques like meditation, nature walks, and getting enough sleep can go a long way in shoring up an individual’s ability to manage stress.61 An additional focus on a healthy diet and consistent exercise can also help enhance the body’s stress response while concurrently providing other health-promoting benefits as described previously.

Psychosocial

It is now currently accepted that health is not merely the absence of disease. This is also true among cancer survivors. In some studies, psychosocial well-being is more predictive of recurrence than stage of diagnosis.62
 
The impact of psychological well-being and perceived quality of life is critical to the healing process among cancer survivors.63 Psychosocial factors such as isolation/support, purpose, optimism, and hope are strongly connected to outcomes as they relate to cancer survivorship. For example, hopelessness is linked to increased mortality among people diagnosed with cancer.64 Positive thinking and positive affirmations can impact both mental and physical health, and optimistic people have been shown to have higher quality of life and cope better with stress.65,66
 
Newer research involving the study of eudaimonic (focusing on meaning and self-realization) wellness compared to hedonic (focusing on pleasure) wellness indicates that individuals who feel their life has purpose also have reduced chronic inflammation and tumor progression, as well as healthier stress responses and sleep patterns.67,68
 
The negative physiological effects of social isolation as they relate to cancer progression have been widely documented in the scientific research. A 2012 study involving ovarian cancer survivors demonstrated significantly improved clinical outcomes in women who had strong social support compared to those who felt isolated.69 Previous studies published by these same authors demonstrated an association between low levels of social support and increased inflammation, angiogenesis, and invasion.70,53 Individuals with strong social support are also more resilient and can manage the effects of stress better than individuals who feel isolated.71 The authors of a 2016 review concluded that “social environment contributes to the vast individual differences in prognosis among breast cancer survivors because social environment is capable of altering basic physiological processes, which in turn can modulate tumor growth.”72
 
Social support, optimism, purpose, and hope are just a few aspects of the psychosocial landscape of the cancer survivor that can influence disease outcomes, healing, and quality of life. Addressing these issues is critical for the cancer survivor and should be part of a comprehensive lifestyle plan.

Conclusion

Estimates indicate that the number of cancer survivors in the United States will grow to nearly 19 million by 2024.73 Of the 14.5 million American cancer survivors who were alive in 2014, 64% were long-term survivors, alive 5 or more years after diagnosis.74 Given the increasing number of both long-term and newly diagnosed cancer survivors, attention to their special health needs and reducing risk of recurrence becomes critical. 
 
Numerous studies now demonstrate that a healthy lifestyle that includes a whole foods diet, weight control, smoking cessation, psychosocial support, reduced toxin exposure, and physical activity can counter some of the adverse effects of cancer treatment and reduce recurrence risk while enhancing overall quality of life.75,76
 
Many cancer survivors are highly motivated and, when given the right tools, can become proactive in their recovery and healing process. Many are also receptive to receiving lifestyle strategies that will positively impact their health. A successful approach to survivorship requires attention to all 3 aspects of the CoC survivorship mandate: treatment summary, follow-up care, and proactive personalized lifestyle strategies with the goal of tertiary prevention. This broad educational and clinical intervention will help maximize conventional treatments, enhance quality of life, and reduce the risk of recurrence among this patient population with highly specialized needs.

About the Authors

Lise Alschuler, ND, FABNO, is a naturopathic physician with board certification in naturopathic oncology. She maintains a part-time naturopathic oncology practice with Naturopathic Specialists in Scottsdale, Arizona. Her undergraduate degree in medical anthropology is from Brown University and her naturopathic doctorate is from Bastyr University. She is the coauthor of The Definitive Guide to Cancer and The Definitive Guide to Thriving After Cancer. Alschuler is the chief medical officer of the iTHRIVE Plan.

Matt Mumber, MD, is a board certified radiation oncologist with the Harbin Clinic in Rome, Georgia. He received his medical doctorate from the University of Virginia and he also did a fellowship in integrative medicine with the University of Arizona. He is the coauthor of the book Sustainable Wellness and the editor of the textbook Integrative Oncology: Principles and Practice. Mumber is the director of medical affairs of the iTHRIVE Plan.

Karolyn A. Gazella has been writing and publishing integrative health information since 1992. She is the publisher of the Natural Medicine Journal and the author or coauthor of hundreds of articles and several booklets and books including her latest book The Definitive Guide to Thriving After Cancer that she wrote with Lise Alschuler, ND, FABNO. Gazella is the co-creator and Chief Executive Officer of the iTHRIVE Plan, an innovative online wellness program specifically for cancer survivors.

References

  1. American Cancer Society. Cancer Treatment and Survivorship Facts & Figures 2016-2017. Atlanta, GA: American Cancer Society; 2016.
  2. Commission on Cancer. Cancer Program Standards 2012: Ensuring Patient-Centered Care V 1.2.1. Chicago, IL: American College of Surgeons; 2012.
  3. Institute of Medicine of the National Academies. Fact Sheet : Cancer Survivorship Care Planning November, 2005. Washington, DC: National Academy of Sciences; 2005.
  4. Deline M. The CoC clarifies the survivorship care plan standard: What you need to know. Oncology Rounds. Advisory Board Web site: https://www.advisory.com/research/oncology-roundtable/oncology-rounds/2014/09/the-coc-clarifies-the-survivorship-care-plan-standard-what-you-need-to-know. Published April 25, 2016. Accessed October 27, 2016.
  5. Commission on Cancer. Cancer Program Standards: Ensuring Patient-Centered Care 2016 Edition. Chicago, IL: American College of Surgeons; 2015.
  6. Salz T, Baxi S. Moving survivorship care plans forward: focus on care coordination.Cancer Med. 2016;5(7). 
  7. Nolte L, Kinnane N, Lai-Kwon J, Gates P, Shilkin P, Jefford M. The impact of survivorship care planning on patients, general practitioners, and hospital-based staff. Cancer Nurs. 2016;39(6):E26-E35. 
  8. Boyes AW, Girgis A, D’Este C, Zucca AC. Prevalence and correlates of cancer survivors’ supportive care needs 6 months after diagnosis: a population-based cross-sectional study. BMC Cancer. 2012;12:150.
  9. McDowell ME, Occhipinti S, Ferguson M, Dunn J, Chambers SK. Predictors of change in unmet care needs in cancer. Psychooncology. 2010;19(5):508-516.
  10. Burg M, Adorno G, Lopez E, et al. Current unmet needs of cancer survivors: analysis of open-ended responses to the American Cancer Society Study of Cancer Survivors II. Cancer. 2015;121(4):623-630.
  11. Hofman M, Ryan JL, Figueroa-Moseley CD, Jean-Pierre P, Morrow GR. Cancer-related fatigue: the scale of the problem. Oncologist. 2007;12(Suppl 1):4-10.
  12. Fiorentino L, Ancoli-Israel S. Sleep dysfunction in patients with cancer. Curr Treat Options Neurol. 2007;9(5):337-346.
  13. Janelsins MC, Kohli S, Mohile SG, Usuki K, Ahles TA, Morrow GR. An update on cancer- and chemotherapy-related cognitive dysfunction: current status. Semin Oncol. 2011;38(3):431-438. 
  14. Wang X, Walitt B, Saligan L, Tiwari AF, Cheung CW, Zhang ZJ. Chemobrain: a critical review and causal hypothesis of link between cytokines and epigenetic reprogramming associated with chemotherapy. Cytokine. 2015;72(1):86-96.
  15. Butow PN, Bell ML, Smith AB, et al. Conquer fear: protocol of a randomized controlled trial of a psychological intervention to reduce fear of cancer recurrence. BMC Cancer. 2013;13:201.
  16. Nicolaije KA, Ezendam NP, Vos MC, et al. Impact of an automatically generated cancer survivorship care plan on patient-reported outcomes in routine clinical practice: longitudinal outcomes of a pragmatic, cluster randomized trial. J Clin Oncol. 2015;33(31):3550-3559. 
  17. Denlinger CS, Ligibel JA, Are M, et al. Survivorship: nutrition and weight management, version 2.2014: clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2014;12(10):1396-1406.
  18. Wang Q, Hao J, Guan Q, Yuan W. The Mediterranean diet and gastrointestinal cancers risk. Recent Pat Food Nutr Agric. 2014;6(1):23-26. 
  19. Tortajada-Ferris J, Berbel-Tornero O, Garcia-Castell J, et al. Dietetic factors associated with prostate cancer: protective effects of Mediterranean Diet (in Spanish). Actas Urol Esp. 2012;36(4):239-245.
  20. Toledo E, Salas-Salvado J, Donat-Vargas C, et al. Mediterranean diet and invasive breast cancer risk among women at high cardiovascular risk in the PREDIMED trial: a randomized clinical trial. JAMA Intern Med. 2015;175(11):1752-1760.
  21. Grosso G, Buscemi S, Galvano F, et al. Mediterranean diet and cancer: epidemiological evidence and mechanism of selected aspects. BMC Surg. 2013;13(Suppl 2):S14.
  22. Leenders M, Sluijs I, Ros MM, et al. Fruit and vegetable consumption and mortality: European prospective investigation into cancer and nutrition. Am J Epidemiol. 2013;178(4):590-602.
  23. Oyebode O, Gordon-Dseagu V, Walker A, Mindell JS. Fruit and vegetable consumption and all-cause, cancer and CVD mortality: analysis of Health Survey for England data. J Epidemiol Community Health. 2014;68(9):856-862.
  24. Baumgarten SC, Frasor J. Minireview: Inflammation: an instigator of more aggressive estrogen receptor (ER) positive breast cancers. Mol Endocrinol. 2012;26(3):360–371.
  25. Pollard JW. Macrophages define the invasive microenvironment in breast cancer. J Leukoc Biol. 2008;84(3):623–630.
  26. Fabian CJ, Kimler BF, Hursting SD. Omega-3 fatty acids for breast cancer prevention and survivorship. Breast Cancer Res. 2015;17(1):62.
  27. Braakhuis AJ, Campion P, Bishop KS. Reducing breast cancer recurrence: the role of dietary polyphenolics. Nutrients. 2016 Sep 6;8(9). pii: E547.
  28. Hardman RJ, Kennedy G, Macpherson H, Scholey AB, Pipingas A. A randomized controlled trial investigating the effects of Mediterranean diet and aerobic exercise on cognition in cognitively healthy older people living independently within aged care facilities: the lifestyle intervention in independent living aged care (LIILAC) study protocol. Nutrition Journal. 2015;14:53.
  29. Skarupski KA, Tangney CC, Li H, Morris MC. Mediterranean diet and depressive symptoms among older adults over time. J Nutr Health Aging. 2013;17(5):441-445.
  30. Ballard-Barbash R, Friedenreich CM, Courneya KS, et al. Physical activity, biomarkers, and disease outcomes in cancer survivors: a systematic review. J Natl Cancer Inst. 2012;104(11):815-840. 
  31. Mustian KM, Sprod LK, Janelsins M, Peppone LJ, Mohile S. Exercise recommendations for cancer-related fatigue, cognitive impairment, sleep problems, depression, pain, anxiety, and physical dysfunction: a review. Oncol Hematol Rev. 2012;8(2):81-88.
  32. National Comprehensive Cancer Network. Patient and Caregiver Resources: Exercising During Cancer Treatment. https://www.nccn.org/patients/resources/life_with_cancer/exercise.aspx. Accessed June 11, 2016.
  33. Rao AV, Cohen HJ. Fatigue in older cancer patients: etiology, assessment, and treatment. Semin Oncol. 2008;35(6):633-642.
  34. Kuchinski AM, Reading M, Lash AA. Treatment-related fatigue and exercise in patients with cancer: a systemic review. Medsurg Nurs. 2009;18(3):174-180.
  35. Kushi LH, Doyle C, McCullough M, et al. American Cancer Society Guidelines on nutrition and physical activity for cancer. CA Cancer J Clin. 2012;62(1):30-67. 
  36. Payne JK, Heid J, Thorpe J, Shaw H. Effect of exercise on biomarkers, fatigue, sleep disturbances, and depressive symptoms in older women with breast cancer receiving hormonal therapy. Oncol Nurs Forum. 2008;35(4):635-642.
  37. Bicego D, Brown K, Ruddick M, et al. Effects of exercise on quality of life in women living with breast cancer: a systemic review. Breast J. 2009;15(1):45-51.
  38. Courneya KS, Friedenreich CM, Quinney HA, et al. A randomized trial of exercise and quality of life in colorectal cancer survivors. Eur J Cancer Care (Engl). 2003;12(4):347-357.
  39. Monga U, Garber SL, Thornby J, et al. Exercise prevents fatigue and improves quality of life in prostate cancer patients undergoing radiotherapy. Arch Phys Med Rehabil. 2007;88(11):1416-1422.
  40. National Institute of Environmental Health Sciences. Endocrine Disruptors. National Institute of Environmental Health Sciences. 2010. http://www.niehs.nih.gov/health/materials/endocrine_disruptors_508.pdf
  41. Macon MB, Fenton SE. Endocrine disruptors and the breast: early life effects and later life disease. J Mammary Gland Biol Neoplasia. 2013;18(1):43-61.
  42. Prins GS. Endocrine disruptors and prostate cancer risk. Endocr Relat Cancer. 2008;15(3):649-656.
  43. Rudel RA, Perovich LJ. Endocrine disrupting chemicals in indoor and outdoor air. Atmos Environ. 2009;43(1):170-181.
  44. DellaValle C. Rethinking Carcinogens: new view of cancer development focuses on subtle, combine effects. Environmental Working Group Web site. http://www.ewg.org/research/rethinking-carcinogens EWG. Published July 16, 2015. Accessed October 28, 2016.
  45. Moreno-Smith M, Lutgendorf SK, Sood AK. Impact of stress on cancer metastases. Future Oncol. 2010;6(12):1863-1881.
  46. Thaker PH, Han LY, Kamat AA, et al. Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma. Nat Med. 2006;12(8):939–944.
  47. Mercurio AM, Rabinovitz I. Towards a mechanistic understanding of tumor invasion--lessons from the alpha6beta 4 integrin. Semin Cancer Biol. 2001;11(2):129-141.
  48. Sood AK, Bhatty R, Kamat AA, et al. Stress hormone-mediated invasion of ovarian cancer cells. Clin Cancer Res. 2006; 12(2):369-375.
  49. Antonova L, Aronson K, Mueller CR. Stress and breast cancer: from epidemiology to molecular biology. Breast Cancer Res. 2011;13(2):208.
  50. Lutgendorf SK, Sood AK, Anderson B. Social support, psychological distress, and natural killer cell activity in ovarian cancer. J Clin Oncol. 2005;23(28):7105–7113.
  51. Sephton SE, Sapolsky RM, Kraemer HC, Spiegel D. Diurnal cortisol rhythm as a predictor of breast cancer survival. J Natl Cancer Inst. 2000;92(12):994–1000.
  52. Levy SM, Herberman RB, Whiteside T, Sanszo K, Lee J, Kirkwood J. Perceived social support and tumor estrogen/progesterone receptor status as predictors of natural killer cell activity in breast cancer patients. Psychosom Med. 1990;52(1):73–85.
  53. Hoffman CJ, Ersser SJ, Hopkinson JB, et al. Effectiveness of mindfulness-based stress reduction in mood, breast- and endocrine-related quality of life, and well-being in stage 0 to III breast cancer: a randomized, controlled trial. J Clin Oncol. 2012;30(12):1335-1342.
  54. Carlson LE, Ursalick Z, Goodey E, et al. The effects of mindfulness meditation-based stress reduction program on mood and symptoms of stress in cancer outpatients: 6-month follow up. Support Care Cancer. 2001;9(2):112-123.
  55. Carlson LE. Mindfulness-based interventions for coping with cancer. Ann N Y Acad Sci. 2016;1373(1):5-12.
  56. Varvogli L, Darviri C. Stress management techniques: evidence-based procedures that reduce stress and promote health. Health Science Journal. 2011;5(2):74-89.
  57. van den Berg MM, Maas J, Muller R, et al. Autonomic nervous system responses to viewing green and built settings: differentiating between sympathetic and parasympathetic activity. Int J Environ Res Public Health. 2015;12(12):15860–15874.
  58. Bratman GN, Hamilton JP, Hahn KS, Daily GC, Gross JJ. Nature experience reduces rumination and subgenual prefrontal cortex activation. Proc Natl Acad Sci U S A. 2015;112(28):8567-8572.
  59. Ancoli-Israel S. Recognition and treatment of sleep disturbances in cancer. J Clin Oncol. 2009;27(35):5864-5866.
  60. Basta M, Chrousos GP, Vela-Bueno A, Vgontzas AN. Chronic insomnia and stress system. Sleep Med Clin. 2007;2(2):279-291.
  61. Greenlee H, Balneaves LG, Carlson LE, et al. Clinical practice guidelines on the use of integrative therapies as supportive care in patients treated for breast cancer. J Natl Cancer Inst Monogr. 2014;50:346-358.
  62. Prinsloo S, Wei Q, Scott SM, et al. Psychological states, serum markers and survival: associations and predictors of survival in patients with renal cell carcinoma. J Behav Med. 2015;38(1):48-56.
  63. Anderson BL, Yang HC, Farrar WB, et al. Psychological intervention improves survival for breast cancer patients: a randomized clinical trial. Cancer. 2008; 113(12):3450-3458.
  64. Everson SA, Goldberg DE, Kaplan GA, et al. Hopelessness and risk of mortality and incidence of myocardial infarction and cancer. Psychosom Med. 1996; 58(2):113-121.
  65. Conversano C, Rotondo A, Lensi E, et al. Optimism and its impact on mental and physical well-being. Clin Pract Epidemiol Ment Health. 2010;6:25-29.
  66. Rajandram RK, Ho SM, Samman N, et al. Interaction of hope and optimism with anxiety and depression in a specific group of cancer survivors: a preliminary study. BMC Res Notes. 2011;4:519.
  67. Davis LZ, Slavich GM, Thaker PH, et al. Eudaimonic well-being and tumor norepinephrine in patients with epithelial ovarian cancer. Cancer. 2015;121(19):3543-3550.
  68. Thornton LM, Anderson BL, Schuler T, Carson WE. A psychological intervention reduces inflammation correlates by alleviating depressive symptoms: secondary analysis of a randomized controlled trial. Psychosom Med. 2009;71(7):715-724.
  69. Lutgendorf SK, De Geest K, Bender D, et al. Social influences on clinical outcomes of patients with ovarian cancer. J Clin Oncol. 2012;30(23):2885-2890.
  70. Costanzo ES, Lutgendorf SK, Sood AK, et al. Psychosocial factors and interleukin-6 among women with advanced ovarian cancer. Cancer. 2005;104(2):305-313.
  71. Ozbay F, Johnson DC, Dimoulas E, et al. Social support and resilience to stress. Psychiatry (Edgmont). 2007;4(5):35-40.
  72. Hinzey A, Guadier-Diaz MM, Lustberg MB, DeVries AC. Breast cancer and social environement: getting by with a little help from our friends. Breast Cancer Research. 2016;18(1):54.
  73. DeSantis CE, Lin CC, Mariotto AB, et al. Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin. 2014;64(4):252-271.
  74. American Cancer Society. Cancer Treatment and Survivorship Facts & Figures 2014-2015. Atlanta, GA: American Cancer Society; 2014. 
  75. Pekmezi DW, Demark-Wahnefried W. Updated evidence in support of diet and exercise interventions in cancer survivors. Acta Oncol. 2011;50(2):167–178.
  76. Vijayvergia N, Denlinger CS. Lifestyle factors in cancer survivorship: where we are and where we are headed. J Pers Med. 2015;5(3):243-263.