Updated Evidence in Support of Diet and Exercise Interventions in Cancer Survivors

doi:10.3109/0284186X.2010.529822

Acta Oncol. Author manuscript; available in PMC 2012 February 1.

Published in final edited form as:

Acta Oncol. 2011 February; 50(2): 167–178.

Published online 2010 November 24. doi: 10.3109/0284186X.2010.529822

PMCID: PMC3228995

NIHMSID: NIHMS330503

Updated Evidence in Support of Diet and Exercise Interventions in Cancer Survivors

Dorothy W. Pekmezi and Wendy Demark-Wahnefried

University of Alabama at Birmingham, Birmingham, Alabama, USA

Corresponding author: Wendy Demark-Wahnefried, PhD, RD, Mailing Address: NP 2514, 1530 3rd Ave S, Birmingham, AL, USA 35294-3360, Telephone: 205.975.4022, Fax: 205.934.7049, demark/at/uab.edu

The publisher's final edited version of this article is available at Acta Oncol

See other articles in PMC that cite the published article.

Abstract

Background

A growing body of evidence suggests that diet and exercise behaviors and body weight status influence health-related outcomes after a cancer diagnosis. This review synthesizes the recent progress in lifestyle interventions in light of current guidelines put forth by the American Cancer Society (ACS), the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) and the American College of Sports Medicine (ACSM).

Methods

The PubMed database was searched for terms of cancer survivor(s) or neoplasms/survivor, cross-referenced with MeSH terms of life style, health behavior, physical activity, exercise, body weight, obesity, weight loss, diet, nutrition, and intervention studies and limited to randomized controlled trials (RCTs) that had retention rates exceeding 75%.

Results

There has been an increase in the number and methodological rigor of the studies in this area, with 21 RCTs identified in the past three years. Results suggest that physical activity interventions are safe for cancer survivors and produce improvements in fitness, strength, physical function, and cancer-related psychosocial variables, whereas dietary interventions improve diet quality, nutrition-related biomarkers and body weight. Preliminary evidence also suggests that diet and exercise may positively influence biomarkers associated with progressive disease and overall survival (e.g. insulin levels, oxidative DNA damage, tumor proliferation rates).

Discussion

The evidence base regarding health-related benefits of increased physical activity, an improved diet and weight control continues to expand. Due to the large (and increasing) number of cancer survivors, more research is needed that tests the impact of lifestyle change on health-related outcomes in this population, especially research that focuses on high-reach, sustainable interventions that recruit diverse, representative samples to help increase the generalizability of findings to the population at large. Concurrent research also needs to address relative benefit in relation to various subpopulations as defined by phenotype, genotype, and/or exposures to treatment, and other lifestyle and environmental factors.

Introduction

According to the most recent 2008 compilation of cancer statistics by the International Agency for Cancer Research through the GLOBOCAN Project, there were 12.7 million new cancer cases and 7.6 million cancer deaths worldwide [1]. With continual advances in early detection and treatment, the differential between cancer incidence and mortality is ever-expanding, and with each passing year the number of cancer survivors increases dramatically. Five years ago, Parkin and colleagues reported that the number of cancer survivors in the world totaled over 24.5 million [2]; today, the number is far greater. Although these statistics are encouraging, it is important to acknowledge that the impact of cancer is significant and associated with several long-term health and psychosocial sequelae [3]. In addition to risk for recurrence, data clearly show that compared with general age- and race-matched populations, cancer survivors are at greater risk for developing second malignancies, cardiovascular disease, diabetes, osteoporosis, and functional decline [3]. These comorbid conditions and competing causes of death and disability are believed to result from cancer treatment, genetic predisposition, and/or common lifestyle factors [3].

Lifestyle interventions that promote improvements in diet and exercise behaviors have been proposed as a means to ameliorate the adverse effects of cancer and its treatment [3]. Various organizations, such as the American Cancer Society (ACS), the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) and most recently, the American College of Sports Medicine (ACSM) have issued guidelines for diet and/or physical activity that target cancer survivors [4–6]. These reports serve as resources for health care providers, patient advocates, and other stakeholders to improve the health and well-being of this rapidly expanding and high risk population. Table 1. features excerpts of these compiled guidelines (note that recommendations for alcohol have been omitted since this review is focused solely on diet and exercise). It should be noted, however that each of these reports points to the relative dearth of data on which their current recommendations rest – thus, the infusion of new data is exceptionally important in order to improve our knowledge of the potential benefits of lifestyle change after the diagnosis of cancer, as well as to gain an understanding of the optimal means for promoting behavioral change in this patient population. The goal of this paper is to review these recommendations in light of recent studies that have emerged within the past few years.

Table 1

Compiled Guidelines: American Cancer Society 2006 Guidelines on Nutrition and Physical Activity for Cancer Prevention, the World Cancer Research Fund/American Institute for Cancer Research Recommendations for the Prevention of Cancer, 2007, and the American (more ...)

Methods

This article builds on a previous review of Demark-Wahnefried and Jones (2008) and provides an updated search of literature published on adult cancer survivors from November 2007 to June 2010. The PubMed database was used to perform this review and employed search terms of cancer survivor(s) or neoplasms/survivor cross-referenced with MeSH terms of life style, health behavior, physical activity, exercise, body weight, obesity, weight loss, diet, nutrition, and intervention studies. Because prospective intervention studies that employ a randomized controlled design offer the strongest evidence regarding potential benefit, we have limited our search to randomized controlled trials (RCTs) that employed health-related endpoints, and have further confined our review to trials with rates of attrition less than 25% (in an effort to remove trials that are subject to bias and results that may not be generalizable). A brief summary of these studies [7–31] is included in Table 2.

Table 2

Randomized Controlled Trials (RCTs) of lifestyle interventions for cancer survivors

Results

Weight Management

At the forefront of both the ACS and the WCRF/AICR recommendations are guidelines for weight control [4, 5].While both organizations currently differ regarding cutpoints that distinguish a desirable weight, both advocate weight loss if individuals are overweight or obese, and also endorse avoidance of weight gain in adulthood. These guidelines emanate from a large body of epidemiologic findings that have consistently found associations between overweight and obesity and the primary risk of cancer, as well as cancer-related mortality – data which are expanding at a rapid pace as the world’s population becomes increasingly overweight. Thus, in contrast to a decade ago when the maintenance of adequate nutrition was the primary concern for individuals diagnosed with cancer, as the obesity epidemic has expanded and as individuals are being diagnosed with cancer at earlier stages, overnutrition has eclipsed undernutrition in terms of prevalence in this patient population. Therefore, in their guide for informed choices, the ACS provides guidelines for weight loss both during and after cancer treatment. While there has yet to be a trial of a weight loss intervention in relation to cancer-related death or recurrence, the number of weight loss interventions among cancer survivors appears to be increasing. During the time circumscribed for this review, there have been three trials that specifically promoted weight loss among survivor populations [10, 11, 14], and one trial that has focused on prevention of weight gain and increased adiposity post-diagnosis [9]. These trials have ranged in size from 24 [14] to 641 [10], targeted a wide range of cancers (e.g., breast, colorectal, endometrial, and prostate), utilized different modes of delivery, and ranged in duration from 6 months [9] to 2-years [10].

The diet-based pilot study by Djuric and colleagues utilized group classes to promote weight loss in obese African-American breast cancer survivors using either a Weight Watcher® based-approach or an approach that incorporated spirituality. While no differences were observed between study arms with regard to weight, participants assigned to the spirituality-based intervention reported significant improvements in fruit and vegetable consumption [14].

In contrast, the other weight management studies employed multi-component interventions that incorporated both diet and exercise elements. These interventions targeted cancer survivors across the cancer continuum, from those who were newly diagnosed and undergoing treatment [9], to those within 5-years of diagnosis [11], as well as those who were long-term survivors, i.e., five or more years beyond diagnosis [10]. The feasibility study conducted by Demark-Wahnefried et al. (2008) employed a distance medicine-based approach of mailed materials and telephone counseling to prevent gains in adiposity that commonly occur during adjuvant chemotherapy. Findings provide support that adverse changes in body composition may be mitigated with a diet-exercise intervention, but that it may be difficult to promote physical activity with home-based approaches during treatment, especially in breast cancer patients who are sedentary prior to diagnosis [9]. In contrast, von Gruenigan and colleagues (2008) found that weight status can be significantly improved with a diet and exercise intervention that utilizes mixed modes of delivery, e.g., group classes, telephone counseling, and mailed print materials, but that improvements in exercise may contribute more to improved body weight status than dietary restriction [11]. Morey et al. (2009) found significant improvements in both diet and exercise behaviors, which translated into significant weight loss, as well as reduced rates of functional decline with a year-long intervention comprised of mailed print materials and telephone counseling among elderly overweight breast, prostate and colorectal cancer survivors [10]. Thus, solid progress is being charted in trials which have used diverse interventions to promote weight loss or weight management among a wide variety of cancer survivors – work that eventually will lay the foundation for trials that explore weight loss in relation to cancer-specific endpoints.

Dietary Patterns

To reinforce the importance of weight management, many of the dietary recommendations put forth by both the ACS and the WCF/AICR advise against the consumption of energy dense foods, i.e., sugars, fats, and a variety of processed foods (Table 1). Instead, the guidelines endorse the consumption of a plant-based diet that focuses on fruits, vegetables and unrefined whole grains, with the WCRF/AICR also cautioning against moldy and salt-cured foods given their association with aerodigestive and hepatic cancers [4].

Recent dietary interventions (see Table 2) have focused on prostate cancer survivors and have monitored biomarkers associated with cancer progression (prostate specific antigen [PSA] levels and/or tumor proliferation rates). A study by Parsons et al. utilized telephone counseling to promote increased consumption of fruits and vegetables over a 6-month study period. Although the intervention elicited excellent adherence and significantly increased consumption, which was confirmed by increases in serum carotenoids, the intervention produced a non-significant increase in PSA that countered the investigators’ hypotheses [15].

Low fat diets also have been explored or tested in newly-diagnosed prostate cancer patients who elect watchful waiting [12] as well as those scheduled for prostatectomy [13]. Results from a small scale 4-week feeding trial performed by Aronson and colleagues (2010) suggested that a low fat diet may inhibit the growth rate of a hormonally-responsive prostate cancer cell line [12]. In contrast, while the low fat diet did promote changes in serum lipids, as well as cytokines and angiogenic factors associated with the NFkB pathway (unpublished data) in a full scale phase II trial by Demark-Wahnefried et al. (2008), dietary fat restriction was not associated as strongly with prostate cancer cell growth as flaxseed supplementation [13]. The mixed results of these dietary intervention trials suggest the need for more research in this area. Indeed the discrepancy in results between two of the largest dietary intervention trials, i.e., the Women’s Intervention Nutrition Study (WINS) (n=2,437) and the Women’s Healthy Eating and Living (WHEL) trials (n=3088), described in the forerunning review [3], as well as the numerous secondary analyses that have emanated from these trials, provides strong evidence that dietary modification may affect subgroups of patients differentially depending upon tumor receptor status, other lifestyle practices, and the specific foods that are consumed (e.g., cruciferous vegetables vs. others).

As with intervention trials aimed at weight management, dietary protocols, such as those that promote a low fat diet and/or increased fruit and vegetable consumption also have been paired with protocols to increase physical activity in multi-component interventions (see Table 2). Bloom et al. (2008) found that group classes were significantly effective in increasing physical activity among breast cancer survivors, but did not influence dietary change [7]. In contrast, Campbell and colleagues (2009) found that home-based approaches that utilize tailored print and/or motivational counseling to improve fruit and vegetable consumption and physical activity among colorectal cancer survivors, have little impact on physical activity, but do improve dietary behaviors [8].

Physical Activity

Overall, ACSM, ACS, and WCF/AICR exercise guidelines for cancer survivors mirror those for the general population by recommending at least 30 minutes of moderate-to-vigorous intensity physical activity on five or more days of the week (see Table 1). The expert panel convened by ACSM further specified that exercise programs may need to be modified for the individual survivor on the basis of his/her health status, treatment history, and anticipated disease trajectory.

Upon reviewing recent physical activity RCTs among cancer survivors (12 studies, Table 2), we observed that these interventions were conducted mostly among breast cancer survivors, with only one study among colorectal cancer survivors [28] and another two involving mixed samples [29, 31]. The interventions described in this review were generally implemented after the participants completed cancer treatments, though one study included participants actively receiving chemotherapy [31]. A combination of individual- and group-based intervention strategies [17, 21, 23, 26, 27, 30] were used in most studies. Others relied solely on individual [20, 24, 28] or group-based approaches [16, 19, 31]. Five interventions focused specifically on aerobic exercise [17, 21, 23, 24, 28], whereas others encouraged resistance training [16, 20] or a combination of aerobic and strength training [26, 29, 31]. A yoga intervention also was included [19]. Recommendations were generally focused on moderate intensity or greater aerobic exercise for at least 150 minutes per week [18, 21, 24, 28] and/or twice weekly strength training sessions for varying durations (90 min. [16, 27]; 30–45 min. [20]) and thus consistent with recent ACSM guidelines for cancer survivors.

Overall, the findings from these studies suggest that exercise is a safe and effective way to provide rehabilitation for cancer survivors and that even brief exercise interventions can be beneficial. Outcomes included improved aerobic capacity [17, 21, 24, 29, 31], strength [16, 22, 27, 31], body composition [17, 21, 26], quality of life [16, 30], as well as reduced fatigue [23, 24, 31], emotional distress [23, 31], lymphedema symptoms [27], and oxidative DNA damage [28].

In terms of progress since the last review [3], several improvements in research design and methodology were noted in these recent studies. First, this literature search uncovered more RCTs than the past review (12 vs. 4, respectively). The trend away from quasi-experimental designs is encouraging, as methodologically rigorous designs allow for more confidence in results. However, sample sizes were still relatively small, ranging from 37–269 (M=124 participants), but appear to be increasing. For example, in the current review, there were six (out of 12) studies with samples of at least 100 participants [7, 8, 13, 16, 26, 27, 29, 31], compared to the last review in which only one (of seven studies) had a sample size greater than 100. Such improvements will help increase statistical power and improve stability of findings.

There also were several differences in the recent physical activity interventions offered to cancer survivors. While the range of intervention lengths varied widely (2 weeks [28] to 2 years [20]) for the studies included in this review, four (out of 12) emphasized long-term (> 6 months) exercise interventions [16, 17, 20, 27] for cancer survivors, compared to only one study (out of the seven) from the past review. Such a shift in program duration will be more conducive to promoting and studying the enduring lifestyle changes in physical activity behavior among cancer survivors needed to beneficially impact rehabilitation and survivorship long-term.

The more recent interventions also tended to be less supervised. Strictly supervised conditions [28, 30, 31] are more easily monitored and may help alleviate participant concerns regarding safety, but any gains may be difficult to maintain once the program ends and the externally imposed structure and support is no longer available. Most studies in this review emphasized a combination of supervised and unsupervised exercise. For example, Fillion et al. (2008) provided supervised instruction with home-based exercise assignments and Rogers (2009) and colleagues attempted to gradually transition participants to home-based exercise by study completion [21, 23]. Such approaches encourage self-management of exercise behavior and favorably influence sustainability. Furthermore, mail and telephone-delivered interventions used by Pinto et al. (2008) have great potential for reaching larger numbers of cancer survivors and positively impacting public health [24].

Another interesting trend was the incorporation of mind-body approaches to wellness into physical activity interventions for cancer survivors. For example, in Adamsen et al. (2009), a high intensity 6-week physical training program was accompanied by relaxation training (progressive muscle relaxation, 30 minutes/4 times a week), body awareness and restorative training (yoga and Pilates, 90 minutes/week), and massage (30 minutes/twice a week) for cancer patients undergoing chemotherapy. Findings indicated significant improvements in vitality, physical functioning, fitness, stress and mental health, as well as reduced fatigue [31]. Another physical activity intervention was combined with nurse-led cognitive-behavioral stress management group sessions (1.5 hours/week for 4 weeks; relaxation training, practicing coping skills for fatigue, discussing connection between thoughts, emotions, and fatigue) for breast cancer survivors and improved fatigue, energy levels, and emotional distress [23].

Additionally, Carson et al. (2009) provided 8 weekly yoga classes with gentle stretching poses, breathing techniques, and meditation and was able to reduce menopausal symptoms, joint pain and sleep in early stage breast cancer patients with hot flashes [19]. Interventions incorporating relaxation training and other psychosocial/wellness components along with physical training appear to be beneficial and can help address the wide range of psychological and physical symptoms experienced by cancer survivors during and after treatment, as well as educate the participants on the nexus between the two (i.e., mind-body connection).

Finally, a few recent studies have begun to examine more than just the usual exercise capacity and quality of life outcomes. Researchers have called for well-designed studies testing the effects of physical activity upon cancer survivorship and/or surrogate/biological markers mediating the association between physical activity and survival [32]. While none of the studies identified in this review specifically examined survival outcomes, there were a few RCTs examining potential physiological mechanisms through which physical activity might impact cancer. For example, the beneficial effects of physical activity on cancer survival may be mediated through a reduction in body fat and beneficial changes in metabolic hormones (insulin), growth factors (insulin-like growth factor IGF-1 and its binding protein IGFBP-3), and adipokines (leptin, adiponectin). In this review, Irwin and c0olleagues (2008) demonstrated that a 6-month aerobic exercise intervention produced statistically significant increases in lean mass and decreases in body fat, insulin levels, IGF-1, and IGFBP-3, whereas women randomized to usual care experienced increases in these biomarkers [17]. Moreover, dose response effects were observed between exercise frequency and decreases in body fat and increases in lean body mass. Insulin levels also were examined by Ligibel and colleagues and found to be significantly reduced (28%) after a 16-week combined strength training and aerobic exercise intervention [26]. However, there were no significant changes found in body composition or adipokines (leptin, total and high molecular weight adiponectin). The authors hypothesized that longer (> 4 months) and/or more strenuous exercise programs may be required to affect these outcomes and called for more studies examining the impact of physical activity on adipokines in cancer survivors.

Another mechanism by which physical activity may exert its influence on cancer risk and prognosis could be through the modulation of oxidative DNA damage, which is implicated not only in carcinogenesis, but also may be important for relapse. Among 48 colorectal cancer patients following primary therapy, a 2-week moderate intensity exercise program reduced oxidative DNA damage as measured by pre- and post-intervention urinary 8-oxo-dG excretion concentrations (8.47±1.99 to 5.91±1.45 ng/mg creatinine, p=0.02), whereas high-intensity exercise tended to increase DNA damage (5.00+1.31 to 7.11+1.63 ng/mg creatinine, p=0.18) [28]. More research is needed to replicate these findings, but these data suggest that exercise recommendations for cancer survivors might warrant a focus on moderate-intensity, rather than vigorous, activities.

Discussion

The number of randomized trials testing lifestyle interventions in cancer survivors is growing, but the evidence base is still limited. This review uncovered more published studies on physical activity interventions for cancer survivors, than those involving dietary modification. Moreover, despite advocacy of multi-component lifestyle interventions, there still are relatively few studies of combined programs. Such approaches may be especially important in pursuing studies that target survival endpoints given that secondary analyses from the WHEL trial suggest a significant survival advantage for breast cancer survivors who exercised 30 minutes, 6 days/week and consumed at least 5 servings/day of fruits and vegetables, which was not seen in women who adopted only one of those health behaviors (physical activity or diet) [33].

Overall, findings from this review indicate that lifestyle interventions for cancer survivors appear to still focus on outcomes related to fitness, diet, and cancer-related psychosocial factors. Physical activity interventions were shown to be safe for cancer survivors and produce improvements in fitness, strength, and quality of life (e.g., fatigue). Likewise, dietary interventions found significant improvements in diet quality, restriction of dietary fat, and increased fruit and vegetable consumption (as well as serum markers associated with these foods). Since the last review, more researchers have started examining the impact of diet and exercise on surrogate/biologic markers of survival [9, 12, 15, 17, 26, 28]. For example, results suggest that physical activity can reduce insulin levels [17, 26] and perhaps oxidative DNA damage [28] in cancer survivors. Additionally, studies are now testing the impact of interventions directly on the biology of the tumor, as in the trial which compared the effects of dietary fat restriction and/or flaxseed supplementation instituted during the presurgical period in 161 men scheduled for prostatectomy, and found lower proliferation rates in excised tumors of men assigned to flaxseed [13].

In terms of future directions, RCTs testing the effects of physical activity and diet on survival have been called for in prior reviews [32] and are still needed. Such studies would provide critical information about whether and how much lifestyle change can affect prognosis. While physicians and health care providers are still encouraged to recommend lifestyle changes to cancer survivors (consistent with the ACS, WCRF/AICR, and ACSM guidelines) on the basis of the beneficial health outcomes from studies summarized in this and past reviews [9], future research will help inform doses (or exposures) that are required and the magnitude of effects that can be expected, as well as uncover possible side effects. Furthermore, subset analyses among survivors with different phenotypes, genotypes and other lifestyle/environmental/treatment exposures may help to personalize lifestyle prescriptions over the long-term.

As this research literature grows, future directions also should focus on sustainable lifestyle interventions that are capable of reaching the large (and increasing) number of cancer survivors. For example, many of the physical activity interventions described in this review were costly and required considerable staff expertise to deliver. From the participant perspective, these programs may invoke unrealistic demands on time and travel that serve as barriers to participation. Future research should focus on developing and testing interventions with potential for sustainability and disseminability in order to serve the growing population of cancer survivors. Also, since most available studies recruited primarily White samples, including other racial/ethnic groups in future trials would help increase the generalizability of such findings to the population at large.

Acknowledgments

This work was supported by Grant No. CA106919 (WDW) and the University of Alabama at Birmingham Comprehensive Cancer Center

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