Randomized trial of weight loss in primary breast cancer: Impact on body composition, circulating biomarkers and tumor characteristics

Demark‐Wahnefried, Wendy; Rogers, Laura Q.; Gibson, Justin T.; Harada, Shuko; Frugé, Andrew D.; Oster, Robert A.; Grizzle, William E.; Norian, Lyse A.; Yang, Eddy S.; Manna, Dipankar; Jones, Lee W.; Azrad, Maria; Krontiras, Helen

doi:10.1002/ijc.32637

Cited by 43 publications

(31 citation statements)

References 49 publications

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“…The remaining five studies applied the weight loss interventions post-cancer treatment and only blood samples were analyzed. When comparing the serum cytokine levels in the weight loss intervention group to the control, TNFα (145,147,148), IL-6 (145,(147)(148)(149), and CRP (148,149) were mainly unchanged. When comparing post-intervention to preintervention, TNFα (146) and CRP (144) were unchanged in one study, while IL-6 was reduced in one study (146).…”

Section: Clinical Findingsmentioning

confidence: 97%

“…All six studies were conducted in cancer patients with overweight or obesity, and weight loss interventions included the combination of PA and ER. Five out of the six studies (144)(145)(146)(147)(148) were conducted in breast cancer patients, and one study (149) recruited patients of a mix of cancer types. One study (145) assessed the effect of a pre-surgical weight loss intervention on serum and intratumoral immune and inflammatory markers.…”

Section: Clinical Findingsmentioning

confidence: 99%

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Impact of physical activity and energy restriction on immune regulation of cancer

Xu¹,

Rogers²

2020

Transl Cancer Res TCR

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Cancer is a major public health issue worldwide. Lifestyle factors, such as body weight and physical activity (PA), significantly impact cancer risk and progression. There is strong evidence that PA reduces and obesity increases risk and mortality from numerous cancer types. Energy restriction (ER) in non-obese hosts significantly reduces tumor incidence in a variety of preclinical models, and reduces body weight and cardiometabolic risk factors in humans. Emerging data suggest that PA-and ER-induced changes in inflammatory and immune mediators may contribute to the cancer prevention effects of these interventions. A systematic literature search was conducted to identify studies that evaluated the impact of PA and ER on tumor and immune outcomes in humans and animal models. A total of 97 eligible studies were identified (68 studies reporting PA interventions and 30 studies reporting ER interventions). Thirtyone studies investigated the effect of PA on cancer immune outcomes using preclinical cancer models of breast (n=17, 55%), gastrointestinal (n=6, 19%), melanoma (n=4, 13%), and several other cancer types (n=4, 13%). Despite the heterogeneity in study designs, the majority of studies (n=23, 74%) reported positive effects of PA on tumor outcomes. Thirty-seven clinical studies investigated the effect of PA on cancer immune outcomes. None reported tumor outcomes, thus only immune outcomes were evaluated in these studies. PA studies were conducted in patients with breast (n=22, 59%), gastrointestinal (n=5, 14%), prostate (n=2, 5%), esophageal (n=1, 3%), lung (n=1, 3%) cancer, leukemia (n=1, 3%), or mixed cancer types (n=5, 14%). Twenty-two studies investigated the effect of ER interventions on cancer immune outcomes using preclinical cancer models including breast (n=5, 23%), gastrointestinal (n=5, 23%), lung (n=2, 9%), liver (n=2, 9%), pancreatic (n=2, 9%), and several other cancer types (n=6, 27%). Positive effects of ER on tumor outcomes were reported in 21 of 22 studies. Six clinical studies investigated the effect of ER (in combination with PA) on tumor immune outcomes in cancer patients with overweight or obesity. Five were conducted in breast cancer patients, and one recruited patients of a mix of cancer types. A wide range of immunological parameters including immune cell phenotype and function, cytokines, and other immune and inflammatory markers were assessed in multiple tissue compartments (blood, spleen, lymph nodes and tumor) in the included studies. Results from preclinical and clinical studies suggest that both PA and ER exert heterogeneous effects on circulating factors and systemic immune responses. PA + ER alters the gene expression profile and immune infiltrates in the tumor which may result in a reduction in immune suppressive factors. However, additional studies are needed to better understand the effect of PA and/or ER on immunomodulation, particularly in the tumor microenvironment (TME).

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Section: Clinical Findingsmentioning

confidence: 97%

Section: Clinical Findingsmentioning

confidence: 99%

Impact of physical activity and energy restriction on immune regulation of cancer

Xu¹,

Rogers²

2020

Transl Cancer Res TCR

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“…Evidence in support comes from randomized and controlled trials implementing behavioral or lifestyle interventions to bring about changes to physiology. For example, one study randomized 32 overweight or obese stage 0-II breast cancer patients into an intervention and control group as part of a 30 day pre-surgery “weight loss” study ( 320 ). The intervention group received counseling on caloric restriction and aerobic exercise to promote a change in body mass of 0.68–0.92 kg/week.…”

Section: The Relevance Of Aging and Lifestyle For Cancer Biomarker Prmentioning

confidence: 99%

A Phenomic Perspective on Factors Influencing Breast Cancer Treatment: Integrating Aging and Lifestyle in Blood and Tissue Biomarker Profiling

et al. 2021

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Breast cancer is the most common malignancy among women worldwide. Over the last four decades, diagnostic and therapeutic procedures have improved substantially, giving patients with localized disease a better chance of cure, and those with more advanced cancer, longer periods of disease control and survival. However, understanding and managing heterogeneity in the clinical response exhibited by patients remains a challenge. For some treatments, biomarkers are available to inform therapeutic options, assess pathological response and predict clinical outcomes. Nevertheless, some measurements are not employed universally and lack sensitivity and specificity, which might be influenced by tissue-specific alterations associated with aging and lifestyle. The first part of this article summarizes available and emerging biomarkers for clinical use, such as measurements that can be made in tumor biopsies or blood samples, including so-called liquid biopsies. The second part of this article outlines underappreciated factors that could influence the interpretation of these clinical measurements and affect treatment outcomes. For example, it has been shown that both adiposity and physical activity can modify the characteristics of tumors and surrounding tissues. In addition, evidence shows that inflammaging and immunosenescence interact with treatment and clinical outcomes and could be considered prognostic and predictive factors independently. In summary, changes to blood and tissues that reflect aging and patient characteristics, including lifestyle, are not commonly considered clinically or in research, either for practical reasons or because the supporting evidence base is developing. Thus, an aim of this article is to encourage an integrative phenomic approach in oncology research and clinical management.

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“…CR-mediated reduction in cancer cell proliferation is central to anti-cancer animal model studies. The clinical trial studies showed no negative energy/calorie restriction effects on cell proliferation marker Ki-67 in Barrett's esophagus [13] and breast cancers [14]. In men with prostate cancer, presurgical weight loss showed CR-mediated Ki-67 upregulation [12].…”

Section: Introductionmentioning

confidence: 98%

“…Recent randomized clinical trials have been explored for potential CR anti-cancer properties [12][13][14]. These trials showed mixture effects of CR directly on tumor tissue growth, host immune cells response, and other tissue responses (e.g., adipocytes).…”

Section: Introductionmentioning

confidence: 99%

Immunity Depletion, Telomere Imbalance, and Cancer-Associated Metabolism Pathway Aberrations in Intestinal Mucosa upon Short-Term Caloric Restriction

Maestri

Duszka

Kuznetsov

2021

Cancers

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Systems cancer biology analysis of calorie restriction (CR) mechanisms and pathways has not been carried out, leaving therapeutic benefits unclear. Using metadata analysis, we studied gene expression changes in normal mouse duodenum mucosa (DM) response to short-term (2-weeks) 25% CR as a biological model. Our results indicate cancer-associated genes consist of 26% of 467 CR responding differential expressed genes (DEGs). The DEGs were enriched with over-expressed cell cycle, oncogenes, and metabolic reprogramming pathways that determine tissue-specific tumorigenesis, cancer, and stem cell activation; tumor suppressors and apoptosis genes were under-expressed. DEG enrichments suggest telomeric maintenance misbalance and metabolic pathway activation playing dual (anti-cancer and pro-oncogenic) roles. The aberrant DEG profile of DM epithelial cells is found within CR-induced overexpression of Paneth cells and is coordinated significantly across GI tract tissues mucosa. Immune system genes (ISGs) consist of 37% of the total DEGs; the majority of ISGs are suppressed, including cell-autonomous immunity and tumor-immune surveillance. CR induces metabolic reprogramming, suppressing immune mechanics and activating oncogenic pathways. We introduce and argue for our network pro-oncogenic model of the mucosa multicellular tissue response to CR leading to aberrant transcription and pre-malignant states. These findings change the paradigm regarding CR’s anti-cancer role, initiating specific treatment target development. This will aid future work to define critical oncogenic pathways preceding intestinal lesion development and biomarkers for earlier adenoma and colorectal cancer detection.

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Randomized trial of weight loss in primary breast cancer: Impact on body composition, circulating biomarkers and tumor characteristics

Cited by 43 publications

References 49 publications

Impact of physical activity and energy restriction on immune regulation of cancer

Impact of physical activity and energy restriction on immune regulation of cancer

A Phenomic Perspective on Factors Influencing Breast Cancer Treatment: Integrating Aging and Lifestyle in Blood and Tissue Biomarker Profiling

Immunity Depletion, Telomere Imbalance, and Cancer-Associated Metabolism Pathway Aberrations in Intestinal Mucosa upon Short-Term Caloric Restriction

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