Mounting evidence underscores the crucial role of weight management and physical activity (PA) in enhancing overall health and well-being while mitigating the risk of morbidity and mortality among cancer survivors. Despite the recognized benefits and existing opportunities to integrate these practices into routine cancer care, significant barriers persist.
Understanding the Landscape
A recent National Academies of Science, Engineering, and Medicine Workshop, "Incorporating Weight Management and Physical Activity throughout the Cancer Care Continuum," addressed key issues related to body weight and PA among cancer survivors, including:
- Current knowledge and gaps in understanding health outcomes.
- Effective intervention approaches.
- Addressing the diverse needs of cancer survivor populations.
- Opportunities and challenges in workforce, care coordination, and technology for program implementation.
- Models of care.
- Program coverage.
Building upon these discussions, a subsequent National Cancer Policy Forum (NCPF) workshop focused on translating research findings into clinical practice and community-based programs, emphasizing behavioral science, clinical research, public policy, dissemination science, and health economics. These workshops underscored the value of promoting weight management and PA across the cancer survivorship period, from diagnosis to end of life, while evaluating current approaches.
To ensure a patient-centered approach, cancer survivors shared their experiences with cancer treatment, weight management, and physical activity. Their voices highlight the importance of individualizing care and addressing the unique challenges faced by each survivor.
The Impact of Body Weight and Physical Activity on Cancer Outcomes
This section critically evaluates the current understanding of the relationship between body weight or PA and health outcomes for cancer survivors, starting with an overview of cancer outcomes and then addressing factors like quality of life (QOL) and fatigue.
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Body Weight and Cancer Risk
Excess weight gain, overweight, and obesity are linked to an increased risk of several cancers. The International Agency for Research on Cancer has concluded that avoiding excess body fat is associated with a lower risk for cancers of the endometrium, esophagus (adenocarcinoma), gastric cardia, kidney (renal cell), multiple myeloma, meningioma, liver, pancreas, colorectum, gallbladder, breast (postmenopausal), ovary, and thyroid. Observational evidence also suggests that obesity is associated with poorer cancer outcomes.
The Link Between Obesity and Breast Cancer
The largest body of evidence connects obesity to breast cancer outcomes. A meta-analysis of 82 studies involving 213,075 women with breast cancer revealed a 41% relative increase in all-cause mortality for women with obesity compared to those of normal weight. This increase was more pronounced in premenopausal women (75%) than in postmenopausal women (34%). Overweight women also experienced increased all-cause mortality, although to a lesser extent.
Biological Complexity
The association between excess weight gain, overweight, and obesity with cancer is biologically complex. Studies examining weight-related changes in the transcriptome of breast cancers indicate that cancers developing in women with obesity are biologically different from those in women of normal weight, with altered gene regulation and expression. It remains unclear whether reversing obesity can reverse these differences or improve cancer outcomes.
Physical Activity and Improved Outcomes
Preliminary evidence suggests that increased PA is linked to improved cancer outcomes. A systematic review and pooled analysis of 26 observational studies found that cancer survivors who engaged in higher levels of PA (>18 MET-hours/week) had a 37% lower risk of dying from cancer compared to those with lower PA levels (<1.5 MET-hours/week). This risk reduction is consistent across breast, colorectal, and prostate cancer survivors. Furthermore, the association between PA and cancer mortality may vary based on specific molecular or genetic markers, suggesting a potential precision medicine approach to exercise oncology.
Ongoing Trials
The Colon Health and Life-Long Exercise Change (CHALLENGE) Trial is a phase III trial examining the effects of a 3-year structured PA program on disease-free survival in patients with stage II and III colon cancer who have recently completed chemotherapy.
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Guidelines and Recommendations
In 2010, the American College of Sports Medicine (ACSM) published PA guidelines for cancer survivors based on 85 PA trials conducted during or post-treatment. These guidelines, along with findings from more recent meta-analyses, demonstrate that PA is safe and effective in improving QOL, cancer-related fatigue, and physical function.
Addressing Critical Gaps in Research
While numerous trials have assessed the impact of weight management and PA interventions on outcomes like body composition, fitness, and QOL in cancer survivors, significant gaps remain. Notably, evidence from RCTs is still lacking to confirm that weight management or increased PA after cancer diagnosis improves survival or reduces cancer recurrence.
The Women's Intervention Nutrition Study
The Women’s Intervention Nutrition Study, involving 2437 women with early-stage breast cancer, suggests that a mean non-prescribed weight loss of six pounds, resulting from a fat-restricted diet, was associated with a significant decrease in subsequent breast cancer events compared to a control arm. However, because the dietary fat intervention also led to weight loss, it is impossible to disentangle whether the low-fat diet or the weight loss was most responsible for cancer control.
Ongoing Trials
Several ongoing trials aim to address these evidence gaps by examining the impact of weight loss or increased PA, alone or in combination with improvements in diet quality, on cancer recurrence, cancer-related mortality, or overall survival in individuals diagnosed with a single malignancy.
Bridging the Evidence Gaps
To bridge these evidence gaps and ensure that all cancer survivors have access to weight management and PA interventions that could reduce the risk of recurrence and improve survival after cancer diagnosis, it is essential to expand the knowledge gained from ongoing individual trials through correlative science and by pooling data and samples across smaller studies. Biomarker analyses offer the potential to extend the knowledge gained from these trials to other patient populations and could ultimately determine the components of optimal interventions and how they are best applied in a personalized medicine approach to improve cancer outcomes.
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Lifestyle Modifications and Weight Management Strategies
Lifestyle modifications to alter eating behaviors and increase PA are the cornerstone of treatment for overweight and obesity and have been used successfully in several large-scale trials. Adherence to a calorically-restricted diet predicts weight loss success, independent of the type of diet or macronutrient composition. The American College of Cardiology (ACC), American Heart Association (AHA), and The Obesity Society (TOS) recommend using body mass index (BMI) and waist circumference to advise patients of their risk of developing other comorbidities and to prescribe a set number of calories per day to promote a 1-2 pound weight loss per week. A sustained weight loss of as little as 3-5% of initial body weight reduces the risk of type II diabetes and risk factors for CVD.
Successful Long-Term Studies
The Look AHEAD (Action for Health in Diabetes) and Diabetes Prevention Program (DPP) trials are two of the most successful long-term studies to illustrate the ability of lifestyle interventions to reduce and maintain body weight and reduce the risk of chronic diseases.
The Importance of Physical Activity
Aerobic PA of sufficient volume and intensity (“exercise”) to improve cardiorespiratory fitness, a potent biomarker of morbidity and all-cause mortality, needs to be frontline care in both healthy and cancer survivor populations. Consistent aerobic exercise can delay the onset of disability by more than 10 years and markedly increases survival among older adults with projected lifespans of at least 20 years. Among cancer survivors, data indicate that high vs. low cardiorespiratory fitness reduces the risk of mortality by 45%. Likewise, resistance PA of sufficient volume and intensity (“exercise”) to increase neuromuscular fitness is key to frontline care.
Molecular Transducers of Physical Activity Consortium (MoTrPAC)
The NIH-funded Molecular Transducers of Physical Activity Consortium (MoTrPAC) is charged with mapping molecular responses to aerobic and resistance exercise to more fully understand the cellular and molecular signals that drive potential health benefits.
Weight Loss Promotion
Data indicate that weight loss can be promoted among cancer survivors who are overweight or have obesity. Sentinel studies of weight management generally rely on cornerstone elements of weight loss (i.e., dietary modification to promote caloric restriction, increased PA, and behavior modification).
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