Table 1.

Summary of the evidence and evidence gaps about research on energy balance and cancer recurrence and survival

EvidenceEvidence gaps
Energy balance and cancer risk
•Consensus for direct associations between obesity and the incidence of the following cancers: endometrial, colorectal, renal, esophageal, pancreatic, and postmenopausal breast.•What is the impact of obesity on the incidence of other cancers or cancer subtypes (inclusive of childhood cancers)?
•Accumulating evidence for direct associations between obesity and the incidence of cancers of the ovary, gallbladder, thyroid, liver, and aggressive forms of prostate cancer, as well as non-Hodgkin lymphoma.•What are the effects of a lifetime of obesity on cancer risk and outcomes?
•Weight loss during adulthood is associated with a reduced incidence of postmenopausal breast cancer.
•Weight gain during adulthood (adult onset obesity) is associated with an increased incidence of postmenopausal breast cancer and colon cancer.
•Obesity is a risk factor for cancer-related mortality from the following cancers: breast, colon, and rectum, cervix, esophagus, gallbladder, kidney, liver, multiple myeloma, non-Hodgkin lymphoma, ovary, pancreas, prostate, stomach, and uterus.
Energy balance and cancer recurrence and promotion
•Obesity at diagnosis is a poor prognostic factor for cancers of the breast, colon, and prostate.•What is the effect of obesity at the time of diagnosis on subsequent prognosis for cancers other than breast, colon, and prostate?
•Are there differential effects of obesity on overall and disease-specific survival by gender, race, ethnicity, comorbidity status (and associated treatment), or various genotypes?
•What are the comparative contributions of increased adiposity, energy intake, or decreased physical activity on cancer recurrence and disease-specific mortality?
•How do obesity-driven events such as stimulated growth factors, cytokines, adipokines, and hormones interact with obesity-related clinicopathologic factors, such as later stage at diagnosis, reduced treatment efficacy, or contribution of comorbid factors (e.g., diabetes) to affect disease-specific and overall outcomes?
•What is the impact of weight change during various stages of neoplasia, for example, preneoplastic lesions, early-stage nonaggressive cancers, later stage aggressive cancers, during active treatment, during the course of disease-free survivorship, and after recurrence or living with active progressive disease?
•How does physical activity during active treatment affect various treatment modalities, including dosing, (dis)continuation of therapy, and efficacy? What is the effect on tumor biology, including angiogenesis and the tumor microenvironment?
Mechanisms of energy balance and cancer promotion
•Several mechanisms have been identified whereby energy balance may affect cancer promotion, including those associated with inflammation, sex steroids, growth factors, and energy-related signaling.•What are the dominant mechanisms and cross-talk between pathways whereby energy balance affects neoplastic progression, and do they vary according to cancer type and stage?
•Obesity-associated metabolic syndrome is associated with some forms of cancer, for example, breast cancer and may support the use of energy-related mimetics, such as metformin, as adjunctive treatment.•Are there additional, yet not well described, effects on molecular pathways, for example, related to DNA repair and the tumor microenvironment?
•Are there discrepancies in cancer–related pathways between animals and humans?
•What are the most appropriate preclinical models to study energy balance and cancer? What are the most appropriate biomarkers to assess within and across models?
•Do agents that target energy-specific pathways, such as metformin, effectively hinder cancer progression?
Energy intake and physical activity and their comparative effects on cancer
•Varying levels of evidence exist about the role of energy balance (and each of its separate components) on cancer incidence and outcomes.•Does energy restriction inhibit cancer progression in humans? What level of restriction is necessary and is negative energy balance best accomplished via intermittent fasting or continual energy restriction?
‐Energy restriction (20%–25% of ad libitum intake) reduces the risk of cancer and cancer progression in animal models.•Do physical activity interventions, either in animal models or in humans, inhibit tumor burden or cancer progression?
‐Exercise interventions in animal models have produced mixed results with regard to cancer development and progression.
‐Human observational data suggest that increased physical activity is associated with lower risk of breast and colorectal cancer, and reduced risk of progression of these cancers.
Weight loss interventions and their applications among cancer survivors
•Much is known about weight loss in healthy populations.•What is the effect of weight loss and long-term weight control on cancer outcomes? What are potential moderators (e.g., treatments, other medications)?
‐Losses of 5%–10% improve risk factors (e.g., glucose control, serum lipids, and blood pressure) that are important for other chronic diseases (e.g., diabetes and CVD).•Are pharmacologic agents commonly used to control diabetes (energy restriction mimetics) helpful in controlling cancer, and what is their comparative effect when tested against energy restriction and/or increased physical activity?
‐A 3-pronged approach of energy restriction, increased physical activity, and behavior modification is recommended, and evidence also supports the use of pharmacologic agents in select populations.•What are the most effective interventions for achieving and maintaining weight loss among cancer survivors and are there differential effects on cancer outcomes that are dependent on the mode of instilling negative energy balance?
‐A growing body of evidence supports bariatric surgery to promote long-term weight control in select populations.•What duration, dose, and frequency of exercise, as well as mode constitute the optimal exercise regimen for creating long-term weight control among cancer survivors?
‐Diet composition does not seem to mediate weight loss success.•Are there potential adverse effects of intervening in cancer survivors? For example, are there survivors who should not do vigorous exercise or lose weight?
‐Greater weight loss is seen with preportioned, structured meals, and meal replacements.•Are there dose responses for weight loss and physical activity? Are there thresholds beyond which the amount or rate of weight loss is not deemed safe for cancer survivors?
‐Greater adherence is observed with more-intensive vs. less-intensive interventions.‐A combination of aerobic and strength training physical activity seems most beneficial in improving body composition.•Are there independent effects of diet composition on cancer-related outcomes?
•Are there other causes of treatment-related weight gain among cancer patients, for example, changes in methylation in promoters of energy-related genes? Which chemotherapeutic agents are associated with the greatest gains in weight and/or adiposity?
•From the weight loss interventions that have been conducted among cancer survivors, many of the same elements (i.e., energy restriction, aerobic and strength training exercise, and behavior modification with cognitive restructuring) seem important, as is grounding in behavioral theory (e.g., social cognitive theory, theory of planned behavior), which endorse tenets such as social support, incremental goal setting with reinforcement, and help with overcoming barriers.
  • What are the effects of weight gain on the tumor microenvironment?

  • What interventions are best able to ameliorate treatment-related weight gain?

  • What are the most cost-effective strategies to promote weight control in cancer survivors?

  • Many questions remain with regard to the dissemination of weight loss interventions:

  • ‐Which cancer survivors should receive them?

  • ‐Who will deliver them?

  • ‐Who will pay for them?

•Many cancer patients gain weight after diagnosis and experience adverse changes in body composition [i.e., loss of lean body mass (muscle and bone) and gain of adipose tissue]. Weight gain is associated with chemotherapy, increased BMI at diagnosis, and younger age, and is partially explained by decreased physical activity during treatment.