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21.01.2021 | Review

Body composition and breast cancer risk and treatment: mechanisms and impact

verfasst von: Toshiaki Iwase, Xiaoping Wang, Tushaar Vishal Shrimanker, Mikhail G. Kolonin, Naoto T. Ueno

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 2/2021

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Abstract

Purpose

The purpose of this review is to clarify the association of body composition with breast cancer risk and treatment, including physiological mechanisms, and to elucidate strategies for overcoming unfavorable body composition changes that relate to breast cancer progression.

Methods

We have summarized updated knowledge regarding the mechanism of the negative association of altered body composition with breast cancer risk and treatment. We also review strategies for reversing unfavorable body composition based on the latest clinical trial results.

Results

Body composition changes in patients with breast cancer typically occur during menopause or as a result of chemotherapy or endocrine therapy. Dysfunction of visceral adipose tissue (VAT) in the setting of obesity underlies insulin resistance and chronic inflammation, which can lead to breast cancer development and progression. Insulin resistance and chronic inflammation are also observed in patients with breast cancer who have sarcopenia or sarcopenic obesity. Nutritional support and a personalized exercise program are the fundamental interventions for reversing unfavorable body composition. Other interventions that have been explored in specific situations include metformin, testosterone, emerging agents that directly target the adipocyte microenvironment, and bariatric surgery.

Conclusions

A better understanding of the biology of body composition phenotypes is key to determining the best intervention program for patients with breast cancer.
Literatur
5.
Zurück zum Zitat Fontanella C, Lederer B, Gade S, Vanoppen M, Blohmer JU, Costa SD, Denkert C, Eidtmann H, Gerber B, Hanusch C, Hilfrich J, Huober J, Schneeweiss A, Paepke S, Jackisch C, Mehta K, Nekljudova V, Untch M, Neven P, von Minckwitz G, Loibl S (2015) Impact of body mass index on neoadjuvant treatment outcome: a pooled analysis of eight prospective neoadjuvant breast cancer trials. Breast Cancer Res Treat 150(1):127–139. https://doi.org/10.1007/s10549-015-3287-5CrossRefPubMed Fontanella C, Lederer B, Gade S, Vanoppen M, Blohmer JU, Costa SD, Denkert C, Eidtmann H, Gerber B, Hanusch C, Hilfrich J, Huober J, Schneeweiss A, Paepke S, Jackisch C, Mehta K, Nekljudova V, Untch M, Neven P, von Minckwitz G, Loibl S (2015) Impact of body mass index on neoadjuvant treatment outcome: a pooled analysis of eight prospective neoadjuvant breast cancer trials. Breast Cancer Res Treat 150(1):127–139. https://​doi.​org/​10.​1007/​s10549-015-3287-5CrossRefPubMed
7.
Zurück zum Zitat Pajares B, Pollan M, Martin M, Mackey JR, Lluch A, Gavila J, Vogel C, Ruiz-Borrego M, Calvo L, Pienkowski T, Rodriguez-Lescure A, Segui MA, Tredan O, Anton A, Ramos M, Camara Mdel C, Rodriguez-Martin C, Carrasco E, Alba E (2013) Obesity and survival in operable breast cancer patients treated with adjuvant anthracyclines and taxanes according to pathological subtypes: a pooled analysis. Breast Cancer Res 15(6):R105. https://doi.org/10.1186/bcr3572CrossRefPubMedPubMedCentral Pajares B, Pollan M, Martin M, Mackey JR, Lluch A, Gavila J, Vogel C, Ruiz-Borrego M, Calvo L, Pienkowski T, Rodriguez-Lescure A, Segui MA, Tredan O, Anton A, Ramos M, Camara Mdel C, Rodriguez-Martin C, Carrasco E, Alba E (2013) Obesity and survival in operable breast cancer patients treated with adjuvant anthracyclines and taxanes according to pathological subtypes: a pooled analysis. Breast Cancer Res 15(6):R105. https://​doi.​org/​10.​1186/​bcr3572CrossRefPubMedPubMedCentral
12.
14.
Zurück zum Zitat Lavigne JA, Goodman JE, Fonong T, Odwin S, He P, Roberts DW, Yager JD (2001) The effects of catechol-O-methyltransferase inhibition on estrogen metabolite and oxidative DNA damage levels in estradiol-treated MCF-7 cells. Cancer Res 61(20):7488–7494PubMed Lavigne JA, Goodman JE, Fonong T, Odwin S, He P, Roberts DW, Yager JD (2001) The effects of catechol-O-methyltransferase inhibition on estrogen metabolite and oxidative DNA damage levels in estradiol-treated MCF-7 cells. Cancer Res 61(20):7488–7494PubMed
15.
Zurück zum Zitat Li KM, Todorovic R, Devanesan P, Higginbotham S, Kofeler H, Ramanathan R, Gross ML, Rogan EG, Cavalieri EL (2004) Metabolism and DNA binding studies of 4-hydroxyestradiol and estradiol-3,4-quinone in vitro and in female ACI rat mammary gland in vivo. Carcinogenesis 25(2):289–297. https://doi.org/10.1093/carcin/bgg191CrossRefPubMed Li KM, Todorovic R, Devanesan P, Higginbotham S, Kofeler H, Ramanathan R, Gross ML, Rogan EG, Cavalieri EL (2004) Metabolism and DNA binding studies of 4-hydroxyestradiol and estradiol-3,4-quinone in vitro and in female ACI rat mammary gland in vivo. Carcinogenesis 25(2):289–297. https://​doi.​org/​10.​1093/​carcin/​bgg191CrossRefPubMed
27.
30.
Zurück zum Zitat van de Velde CJ, Rea D, Seynaeve C, Putter H, Hasenburg A, Vannetzel JM, Paridaens R, Markopoulos C, Hozumi Y, Hille ET, Kieback DG, Asmar L, Smeets J, Nortier JW, Hadji P, Bartlett JM, Jones SE (2011) Adjuvant tamoxifen and exemestane in early breast cancer (TEAM): a randomised phase 3 trial. Lancet (London, England) 377(9762):321–331. https://doi.org/10.1016/s0140-6736(10)62312-4CrossRef van de Velde CJ, Rea D, Seynaeve C, Putter H, Hasenburg A, Vannetzel JM, Paridaens R, Markopoulos C, Hozumi Y, Hille ET, Kieback DG, Asmar L, Smeets J, Nortier JW, Hadji P, Bartlett JM, Jones SE (2011) Adjuvant tamoxifen and exemestane in early breast cancer (TEAM): a randomised phase 3 trial. Lancet (London, England) 377(9762):321–331. https://​doi.​org/​10.​1016/​s0140-6736(10)62312-4CrossRef
34.
Zurück zum Zitat Trayhurn P, Beattie JH (2001) Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ. Proc Nutr Soc 60(3):329–339CrossRefPubMed Trayhurn P, Beattie JH (2001) Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ. Proc Nutr Soc 60(3):329–339CrossRefPubMed
40.
Zurück zum Zitat Deiuliis JA, Oghumu S, Duggineni D, Zhong J, Rutsky J, Banerjee A, Needleman B, Mikami D, Narula V, Hazey J, Satoskar AR, Rajagopalan S (2014) CXCR3 modulates obesity-induced visceral adipose inflammation and systemic insulin resistance. Obesity (Silver Spring, Md) 22(5):1264–1274. https://doi.org/10.1002/oby.20642CrossRef Deiuliis JA, Oghumu S, Duggineni D, Zhong J, Rutsky J, Banerjee A, Needleman B, Mikami D, Narula V, Hazey J, Satoskar AR, Rajagopalan S (2014) CXCR3 modulates obesity-induced visceral adipose inflammation and systemic insulin resistance. Obesity (Silver Spring, Md) 22(5):1264–1274. https://​doi.​org/​10.​1002/​oby.​20642CrossRef
41.
Zurück zum Zitat Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyere O, Cederholm T, Cooper C, Landi F, Rolland Y, Sayer AA, Schneider SM, Sieber CC, Topinkova E, Vandewoude M, Visser M, Zamboni M (2018) Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. https://doi.org/10.1093/ageing/afy169 Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyere O, Cederholm T, Cooper C, Landi F, Rolland Y, Sayer AA, Schneider SM, Sieber CC, Topinkova E, Vandewoude M, Visser M, Zamboni M (2018) Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. https://​doi.​org/​10.​1093/​ageing/​afy169
54.
Zurück zum Zitat Visser M, Pahor M, Taaffe DR, Goodpaster BH, Simonsick EM, Newman AB, Nevitt M, Harris TB (2002) Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women: the Health ABC Study. J Gerontol A Biol Sci Med Sci 57(5):M326–M332CrossRefPubMed Visser M, Pahor M, Taaffe DR, Goodpaster BH, Simonsick EM, Newman AB, Nevitt M, Harris TB (2002) Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women: the Health ABC Study. J Gerontol A Biol Sci Med Sci 57(5):M326–M332CrossRefPubMed
57.
Zurück zum Zitat Caspersen CJ, Powell KE, Christenson GM (1985) Physical activity, exercise, and physical fitness: definitions and distinctions for health-related research. Public Health Rep 100(2):126–131PubMedPubMedCentral Caspersen CJ, Powell KE, Christenson GM (1985) Physical activity, exercise, and physical fitness: definitions and distinctions for health-related research. Public Health Rep 100(2):126–131PubMedPubMedCentral
59.
Zurück zum Zitat Sturgeon K, Digiovanni L, Good J, Salvatore D, Fenderson D, Domchek S, Stopfer J, Galantino ML, Bryan C, Hwang WT, Schmitz K (2016) Exercise-induced dose-response alterations in adiponectin and leptin levels are dependent on body fat changes in women at risk for breast cancer. Cancer Epidemiol Biomarkers Prev 25(8):1195–1200. https://doi.org/10.1158/1055-9965.epi-15-1087CrossRefPubMed Sturgeon K, Digiovanni L, Good J, Salvatore D, Fenderson D, Domchek S, Stopfer J, Galantino ML, Bryan C, Hwang WT, Schmitz K (2016) Exercise-induced dose-response alterations in adiponectin and leptin levels are dependent on body fat changes in women at risk for breast cancer. Cancer Epidemiol Biomarkers Prev 25(8):1195–1200. https://​doi.​org/​10.​1158/​1055-9965.​epi-15-1087CrossRefPubMed
61.
Zurück zum Zitat Dieli-Conwright CM, Courneya KS, Demark-Wahnefried W, Sami N, Lee K, Buchanan TA, Spicer DV, Tripathy D, Bernstein L, Mortimer JE (2018) Effects of aerobic and resistance exercise on metabolic syndrome, sarcopenic obesity, and circulating biomarkers in overweight or obese survivors of breast cancer: a randomized controlled trial. J Clin Oncol 36(9):875–883. https://doi.org/10.1200/jco.2017.75.7526CrossRefPubMedPubMedCentral Dieli-Conwright CM, Courneya KS, Demark-Wahnefried W, Sami N, Lee K, Buchanan TA, Spicer DV, Tripathy D, Bernstein L, Mortimer JE (2018) Effects of aerobic and resistance exercise on metabolic syndrome, sarcopenic obesity, and circulating biomarkers in overweight or obese survivors of breast cancer: a randomized controlled trial. J Clin Oncol 36(9):875–883. https://​doi.​org/​10.​1200/​jco.​2017.​75.​7526CrossRefPubMedPubMedCentral
62.
63.
Zurück zum Zitat Jones LW, Kwan ML, Weltzien E, Chandarlapaty S, Sternfeld B, Sweeney C, Bernard PS, Castillo A, Habel LA, Kroenke CH, Langholz BM, Queensberry CP Jr, Dang C, Weigelt B, Kushi LH, Caan BJ (2016) Exercise and prognosis on the basis of clinicopathologic and molecular features in early-stage breast cancer: the LACE and pathways studies. Cancer Res 76(18):5415–5422. https://doi.org/10.1158/0008-5472.can-15-3307CrossRefPubMedPubMedCentral Jones LW, Kwan ML, Weltzien E, Chandarlapaty S, Sternfeld B, Sweeney C, Bernard PS, Castillo A, Habel LA, Kroenke CH, Langholz BM, Queensberry CP Jr, Dang C, Weigelt B, Kushi LH, Caan BJ (2016) Exercise and prognosis on the basis of clinicopathologic and molecular features in early-stage breast cancer: the LACE and pathways studies. Cancer Res 76(18):5415–5422. https://​doi.​org/​10.​1158/​0008-5472.​can-15-3307CrossRefPubMedPubMedCentral
65.
Zurück zum Zitat Adams SC, Segal RJ, McKenzie DC, Vallerand JR, Morielli AR, Mackey JR, Gelmon K, Friedenreich CM, Reid RD, Courneya KS (2016) Impact of resistance and aerobic exercise on sarcopenia and dynapenia in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial. Breast Cancer Res Treat 158(3):497–507. https://doi.org/10.1007/s10549-016-3900-2CrossRefPubMed Adams SC, Segal RJ, McKenzie DC, Vallerand JR, Morielli AR, Mackey JR, Gelmon K, Friedenreich CM, Reid RD, Courneya KS (2016) Impact of resistance and aerobic exercise on sarcopenia and dynapenia in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial. Breast Cancer Res Treat 158(3):497–507. https://​doi.​org/​10.​1007/​s10549-016-3900-2CrossRefPubMed
68.
70.
Zurück zum Zitat Fuchs CJ, Hermans WJH, Holwerda AM, Smeets JSJ, Senden JM, van Kranenburg J, Gijsen AP, Wodzig W, Schierbeek H, Verdijk LB, van Loon LJC (2019) Branched-chain amino acid and branched-chain ketoacid ingestion increases muscle protein synthesis rates in vivo in older adults: a double-blind, randomized trial. Am J Clin Nutr 110(4):862–872. https://doi.org/10.1093/ajcn/nqz120CrossRefPubMedPubMedCentral Fuchs CJ, Hermans WJH, Holwerda AM, Smeets JSJ, Senden JM, van Kranenburg J, Gijsen AP, Wodzig W, Schierbeek H, Verdijk LB, van Loon LJC (2019) Branched-chain amino acid and branched-chain ketoacid ingestion increases muscle protein synthesis rates in vivo in older adults: a double-blind, randomized trial. Am J Clin Nutr 110(4):862–872. https://​doi.​org/​10.​1093/​ajcn/​nqz120CrossRefPubMedPubMedCentral
71.
Zurück zum Zitat Verlaan S, Maier AB, Bauer JM, Bautmans I, Brandt K, Donini LM, Maggio M, McMurdo MET, Mets T, Seal C, Wijers SLJ, Sieber C, Boirie Y, Cederholm T (2018) Sufficient levels of 25-hydroxyvitamin D and protein intake required to increase muscle mass in sarcopenic older adults—the PROVIDE study. Clin Nutr (Edinburgh, Scotland) 37(2):551–557. https://doi.org/10.1016/j.clnu.2017.01.005CrossRef Verlaan S, Maier AB, Bauer JM, Bautmans I, Brandt K, Donini LM, Maggio M, McMurdo MET, Mets T, Seal C, Wijers SLJ, Sieber C, Boirie Y, Cederholm T (2018) Sufficient levels of 25-hydroxyvitamin D and protein intake required to increase muscle mass in sarcopenic older adults—the PROVIDE study. Clin Nutr (Edinburgh, Scotland) 37(2):551–557. https://​doi.​org/​10.​1016/​j.​clnu.​2017.​01.​005CrossRef
73.
Zurück zum Zitat Checkley LA, Rudolph MC, Wellberg EA, Giles ED, Wahdan-Alaswad RS, Houck JA, Edgerton SM, Thor AD, Schedin P, Anderson SM, MacLean PS (2017) Metformin accumulation correlates with organic cation transporter 2 protein expression and predicts mammary tumor regression in vivo. Cancer Prev Res (Phila) 10(3):198–207. https://doi.org/10.1158/1940-6207.Capr-16-0211-tCrossRef Checkley LA, Rudolph MC, Wellberg EA, Giles ED, Wahdan-Alaswad RS, Houck JA, Edgerton SM, Thor AD, Schedin P, Anderson SM, MacLean PS (2017) Metformin accumulation correlates with organic cation transporter 2 protein expression and predicts mammary tumor regression in vivo. Cancer Prev Res (Phila) 10(3):198–207. https://​doi.​org/​10.​1158/​1940-6207.​Capr-16-0211-tCrossRef
75.
Zurück zum Zitat Hadad S, Iwamoto T, Jordan L, Purdie C, Bray S, Baker L, Jellema G, Deharo S, Hardie DG, Pusztai L, Moulder-Thompson S, Dewar JA, Thompson AM (2011) Evidence for biological effects of metformin in operable breast cancer: a pre-operative, window-of-opportunity, randomized trial. Breast Cancer Res Treat 128(3):783–794. https://doi.org/10.1007/s10549-011-1612-1CrossRefPubMed Hadad S, Iwamoto T, Jordan L, Purdie C, Bray S, Baker L, Jellema G, Deharo S, Hardie DG, Pusztai L, Moulder-Thompson S, Dewar JA, Thompson AM (2011) Evidence for biological effects of metformin in operable breast cancer: a pre-operative, window-of-opportunity, randomized trial. Breast Cancer Res Treat 128(3):783–794. https://​doi.​org/​10.​1007/​s10549-011-1612-1CrossRefPubMed
78.
Zurück zum Zitat Goodwin PJ, Parulekar WR, Gelmon KA, Shepherd LE, Ligibel JA, Hershman DL, Rastogi P, Mayer IA, Hobday TJ, Lemieux J, Thompson AM, Pritchard KI, Whelan TJ, Mukherjee SD, Chalchal HI, Oja CD, Tonkin KS, Bernstein V, Chen BE, Stambolic V (2015) Effect of metformin vs placebo on and metabolic factors in NCIC CTG MA.32. J Natl Cancer Inst 107(3):djv006. https://doi.org/10.1093/jnci/djv006CrossRefPubMedPubMedCentral Goodwin PJ, Parulekar WR, Gelmon KA, Shepherd LE, Ligibel JA, Hershman DL, Rastogi P, Mayer IA, Hobday TJ, Lemieux J, Thompson AM, Pritchard KI, Whelan TJ, Mukherjee SD, Chalchal HI, Oja CD, Tonkin KS, Bernstein V, Chen BE, Stambolic V (2015) Effect of metformin vs placebo on and metabolic factors in NCIC CTG MA.32. J Natl Cancer Inst 107(3):djv006. https://​doi.​org/​10.​1093/​jnci/​djv006CrossRefPubMedPubMedCentral
81.
Zurück zum Zitat Key T, Appleby P, Barnes I, Reeves G (2002) Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst 94(8):606–616CrossRefPubMed Key T, Appleby P, Barnes I, Reeves G (2002) Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst 94(8):606–616CrossRefPubMed
84.
Zurück zum Zitat Gastrointestinal surgery for severe obesity: National Institutes of Health Consensus Development Conference Statement (1991) Am J Clin Nutr 9(1):1–20 Gastrointestinal surgery for severe obesity: National Institutes of Health Consensus Development Conference Statement (1991) Am J Clin Nutr 9(1):1–20
85.
Zurück zum Zitat Andersson DP, Dahlman I, Eriksson Hogling D, Backdahl J, Toft E, Qvisth V, Naslund E, Thorell A, Ryden M, Arner P (2019) Improved metabolism and body composition beyond normal levels following gastric bypass surgery: a longitudinal study. J Intern Med 285(1):92–101. https://doi.org/10.1111/joim.12824CrossRefPubMed Andersson DP, Dahlman I, Eriksson Hogling D, Backdahl J, Toft E, Qvisth V, Naslund E, Thorell A, Ryden M, Arner P (2019) Improved metabolism and body composition beyond normal levels following gastric bypass surgery: a longitudinal study. J Intern Med 285(1):92–101. https://​doi.​org/​10.​1111/​joim.​12824CrossRefPubMed
86.
Metadaten
Titel
Body composition and breast cancer risk and treatment: mechanisms and impact
verfasst von
Toshiaki Iwase
Xiaoping Wang
Tushaar Vishal Shrimanker
Mikhail G. Kolonin
Naoto T. Ueno
Publikationsdatum
21.01.2021
Verlag
Springer US
Erschienen in
Breast Cancer Research and Treatment / Ausgabe 2/2021
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-020-06092-5

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