nach oben

18.05.2024 | Review

The Role of Obesity and Inflammation in Breast Cancer Recurrence

verfasst von: Sonya M. Chew, Bethina Liu, Sherry Shen, Neil M. Iyengar

Erschienen in: Current Breast Cancer Reports

Einloggen, um Zugang zu erhalten

Abstract

Purpose of review

The purpose of this study is to summarize the latest findings regarding the impact of obesity and inflammation on breast cancer recurrence risk.

Recent Findings

Obesity is a risk factor for breast cancer recurrence and cancer-specific mortality. Biologic mechanisms that drive this association vary by tumor subtype and include a dysfunctional tumor microenvironment and systemic inflammation. We discuss the impact of obesity on systemic therapy resistance and review current evidence supporting pharmacological, surgical, and lifestyle modifications for addressing obesity in the context of improving breast cancer survivorship.

Summary

Obesity is associated with poorer survival in breast cancer. Risk stratification by tumor and host-specific characteristics can help identify adjunctive interventions to improve breast cancer outcomes in patients with obesity.

Cancer of the Breast (Female) – Cancer Stat Facts SEER. [cited 2023 Sept 20]. Available from: https://seer.cancer.gov/statfacts/html/breast.html

• Boutari C, Mantzoros CS. A 2022 update on the epidemiology of obesity and a call to action: as its twin COVID-19 pandemic appears to be receding, the obesity and dysmetabolism pandemic continues to rage on. Metabolism. 2022;133:155217. https://doi.org/10.1016/j.metabol.2022.155217. This article highlights the updated incidence and prevalence of obesity worldwide.CrossRefPubMedPubMedCentral

Overweight & Obesity Statistics - NIDDK [cited 2023 Sept 20]. Available from: https://www.niddk.nih.gov/health-information/health-statistics/overweight-obesity

Nishida C, Ko GT, Kumanyika S. Body fat distribution and noncommunicable diseases in populations: overview of the 2008 WHO Expert Consultation on Waist Circumference and Waist-Hip Ratio. Eur J Clin Nutr. 2010;64(1):2–5. https://doi.org/10.1038/ejcn.2009.139.CrossRefPubMed

Aune D, Sen A, Prasad M, Norat T, Janszky I, Tonstad S, et al. BMI and all cause mortality: systematic review and non-linear dose-response meta-analysis of 230 cohort studies with 3.74 million deaths among 30.3 million participants. BMJ. 2016;353:i2156. https://doi.org/10.1136/bmj.i2156.CrossRefPubMedPubMedCentral

• Petrelli F, Cortellini A, Indini A, Tomasello G, Ghidini M, Nigro O, et al. Association of obesity with survival outcomes in patients with cancer: a systematic review and meta-analysis. JAMA Netw Open. 2021;4(3):e213520. https://doi.org/10.1001/jamanetworkopen.2021.3520. This meta-analysis provides an overview of cancer outcomes in obese patients and shows an association of obesity with increased mortality rate.CrossRefPubMedPubMedCentral

Chan DSM, Vieira AR, Aune D, Bandera EV, Greenwood DC, McTiernan A, et al. Body mass index and survival in women with breast cancer-systematic literature review and meta-analysis of 82 follow-up studies. Ann Oncol. 2014;25(10):1901–14. https://doi.org/10.1093/annonc/mdu042.CrossRefPubMedPubMedCentral

Blair CK, Wiggins CL, Nibbe AM, Storlie CB, Prossnitz ER, Royce M, et al. Obesity and survival among a cohort of breast cancer patients is partially mediated by tumor characteristics. NPJ Breast Cancer. 2019;5:33. https://doi.org/10.1038/s41523-019-0128-4.CrossRefPubMedPubMedCentral

• Olsson LT, Walens A, Hamilton AM, Benefield HC, Fleming JM, Carey LA, et al. Obesity and breast cancer metastasis across genomic subtypes. Cancer Epidemiol Biomarkers Prev. 2022;31(10):1944–51. https://doi.org/10.1158/1055-9965.EPI-22-0013. This study reports the incidence of metastasis in obese patients with breast cancer and indicates an increased risk of metastatic recurrence in the setting of obesity.CrossRefPubMedPubMedCentral

10.

von Drygalski A, Tran TB, Messer K, Pu M, Corringham S, Nelson C, et al. Obesity is an independent predictor of poor survival in metastatic breast cancer: retrospective analysis of a patient cohort whose treatment included high-dose chemotherapy and autologous stem cell support. Int J Breast Cancer. 2011;2011:523276. https://doi.org/10.4061/2011/523276.CrossRef

11.

• Saleh K, Carton M, Dieras V, Heudel PE, Brain E, D’Hondt V, et al. Impact of body mass index on overall survival in patients with metastatic breast cancer. Breast. 2021;55:16–24. https://doi.org/10.1016/j.breast.2020.11.014. This observational cohort study indicates that overweight and obesity are not associated with worse outcomes in women with metastatic breast cancer.CrossRefPubMed

12.

Barba M, Pizzuti L, Sperduti I, Natoli C, Gamucci T, Sergi D, et al. Body mass index and treatment outcomes in metastatic breast cancer patients treated with eribulin. J Cell Physiol. 2016;231(5):986–91. https://doi.org/10.1002/jcp.25213.CrossRefPubMed

13.

Iyengar NM, Gucalp A, Dannenberg AJ, Hudis CA. Obesity and cancer mechanisms: tumor microenvironment and inflammation. J Clin Oncol. 2016;34(35):4270–6. https://doi.org/10.1200/JCO.2016.67.4283.CrossRefPubMedPubMedCentral

14.

• Lee-Rueckert M, Canyelles M, Tondo M, Rotllan N, Kovanen PT, Llorente-Cortes et al. Obesity-induced changes in cancer cells and their microenvironment: mechanisms and therapeutic perspectives to manage dysregulated lipid metabolism. Semin Cancer Biol. 2023;6:S1044–579X(23)00076–7. https://doi.org/10.1016/j.semcancer.2023.05.002. This study provides an overview of the progress of research regarding the impact of obesity on the tumor microenvironment and crosstalk with systemic metabolic signaling.

15.

Olson OC, Quail DF, Joyce JA. Obesity and the tumor microenvironment. Science. 2017;358(6367):1130–1. https://doi.org/10.1126/science.aao5801.CrossRefPubMed

16.

Fulbright LE, Ellermann M, Arthur JC. The microbiome and the hallmarks of cancer. PLoS Pathog. 2017;13(9):e1006480. https://doi.org/10.1371/journal.ppat.1006480.CrossRefPubMedPubMedCentral

17.

Urbaniak C, Gloor GB, Brackstone M, Scott L, Tangney M, Reid G. The microbiota of breast tissue and its association with breast cancer. Appl Environ Microbiol. 2016;82(16):5039–48. https://doi.org/10.1128/AEM.01235-16.CrossRefPubMedPubMedCentral

18.

Franceschi C, Garagnani P, Parini P, Giuliani C, Santoro A. Inflammaging: a new immune-metabolic viewpoint for age-related diseases. Nat Rev Endocrinol. 2018;14(10):576–90. https://doi.org/10.1038/s41574-018-0059-4.CrossRefPubMed

19.

•• Nguyen HL, Geukens T, Maetens M, Aparicio S, Bassez A, Borg A, et al. Obesity-associated changes in molecular biology of primary breast cancer. Nat Commun. 2023;14(1):4418. https://doi.org/10.1038/s41467-023-39996-z. This article provides an overview of several genomic alterations that are differentially prevalent in overweight or obese patients compared to lean patients as well as evidence supporting an ageing accelerating effect of obesity at the genetic level.CrossRefPubMedPubMedCentral

20.

Gunter MJ, Hoover DR, Yu H, Wassertheil-Smoller S, Rohan TE, Manson JE, et al. Insulin, insulin-like growth factor-I, and risk of breast cancer in postmenopausal women. J Natl Cancer Inst. 2009;101(1):48–60. https://doi.org/10.1093/jnci/djn415.CrossRefPubMedPubMedCentral

21.

Hetemäki N, Savolainen-Peltonen H, Tikkanen MJ, Wang F, Paatela H, Hämäläinen E, et al. Estrogen metabolism in abdominal subcutaneous and visceral adipose tissue in postmenopausal women. J Clin Endocrinol Metab. 2017;102(12):4588–95. https://doi.org/10.1210/jc.2017-01474.CrossRefPubMed

22.

Sun XZ, Zhou D, Chen S. Autocrine and paracrine actions of breast tumor aromatase. A three-dimensional cell culture study involving aromatase transfected MCF-7 and T-47D cells. J Steroid Biochem Mol Biol. 1997;63(1–3):29–36. https://doi.org/10.1016/s0960-0760(97)00068-x.CrossRefPubMed

23.

Shen S, Iyengar NM. Insulin-lowering diets in metastatic cancer. Nutrients. 2022;14(17):3542. https://doi.org/10.3390/nu14173542.CrossRefPubMedPubMedCentral

24.

• De Santi M, Annibalini G, Marano G, Biganzoli G, Venturelli E, Pellegrini M, et al. Association between metabolic syndrome, insulin resistance, and IGF-1 in breast cancer survivors of DIANA-5 study. J Cancer Res Clin Oncol. 2023. https://doi.org/10.1007/s00432-023-04755-6. This study describes the association between IGF-1 levels and indices of insulin resistance in breast cancer survivors which could be a potential guide for to test strategies that modulate IGF-1 levels.CrossRefPubMedPubMedCentral

25.

Poloz Y, Stambolic V. Obesity and cancer, a case for insulin signaling. Cell Death Dis. 2015;6(12):e2037. https://doi.org/10.1038/cddis.2015.381.CrossRefPubMedPubMedCentral

26.

Key TJ, Appleby PN, Reeves GK, Roddam A, Dorgan JF, Longcope C, Endogenous Hormones Breast Cancer Collaborative, et al. Group Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women. J Natl Cancer Inst. 2003;95(16):1218–26. https://doi.org/10.1093/jnci/djg022.CrossRefPubMed

27.

Goodwin PJ, Ennis M, Pritchard KI, Trudeau ME, Koo J, Madarnas Y, et al. Fasting insulin and outcome in early-stage breast cancer: results of a prospective cohort study. J Clin Oncol. 2002;20(1):42–51. https://doi.org/10.1200/JCO.2002.20.1.42.CrossRefPubMed

28.

Pan K, Chlebowski RT, Mortimer JE, Gunter MJ, Rohan T, Vitolins MZ, et al. Insulin resistance and breast cancer incidence and mortality in postmenopausal women in the Women’s Health Initiative. Cancer. 2020;126(16):3638–47. https://doi.org/10.1002/cncr.33002.CrossRefPubMed

29.

• Ciminera AK, Shuck SC, Termini J. Elevated glucose increases genomic instability by inhibiting nucleotide excision repair. Life Sci Alliance. 2021;4(10):e202101159. https://doi.org/10.26508/lsa.202101159. This article describes the role of hyperglycemia and insulin in promoting genomic instability which in turn is a potential mechanism for increasing cancer risk in metabolic disease.CrossRefPubMedPubMedCentral

30.

• Acevedo F, Walbaum B, Muñiz S, Petric M, Martínez R, Guerra C, et al. Obesity is associated with early recurrence on breast cancer patients that achieved pathological complete response to neoadjuvant chemotherapy. Sci Rep. 2022;12(1):21145. https://doi.org/10.1038/s41598-022-25043-2. This study describes the association of obesity with breast cancer recurrence in the setting of pathologic complete response.CrossRefPubMedPubMedCentral

31.

Hillers-Ziemer LE, Kuziel G, Williams AE, Moore BN, Arendt LM. Breast cancer microenvironment and obesity: challenges for therapy. Cancer Metastasis Rev. 2022;41(3):627–47. https://doi.org/10.1007/s10555-022-10031-9.CrossRefPubMedPubMedCentral

32.

•• Bergman R, Berko YA, Sanchez V, Sanders ME, Gonzalez-Ericsson PI, Arteaga CL, et al. Obesity and metabolic syndrome are associated with short-term endocrine therapy resistance in early ER + breast cancer. Breast Cancer Res Treat. 2023;197(2):307–17. https://doi.org/10.1007/s10549-022-06794-y. This study describes the association of obesity with endocrine therapy resistance and reports a 1.4-fold increased risk of treatment resistance in patients with metabolic syndrome.CrossRefPubMed

33.

Ewertz M, Jensen MB, Gunnarsdóttir KÁ, Højris I, Jakobsen EH, Nielsen D, et al. Effect of obesity on prognosis after early-stage breast cancer. J Clin Oncol. 2011;29(1):25–31. https://doi.org/10.1200/JCO.2010.29.7614.CrossRefPubMed

34.

Dignam JJ, Wieand K, Johnson KA, Fisher B, Xu L, Mamounas EP. Obesity, tamoxifen use, and outcomes in women with estrogen receptor-positive early-stage breast cancer. J Natl Cancer Inst. 2003;95(19):1467–76. https://doi.org/10.1093/jnci/djg060.CrossRefPubMed

35.

Pfeiler G, Königsberg R, Fesl C, Mlineritsch B, Stoeger H, Singer CF, et al. Impact of body mass index on the efficacy of endocrine therapy in premenopausal patients with breast cancer: an analysis of the prospective ABCSG-12 trial. J Clin Oncol. 2011;29(19):2653–9. https://doi.org/10.1200/JCO.2010.33.2585.CrossRefPubMed

36.

Sestak I, Distler W, Forbes JF, Dowsett M, Howell A, Cuzick J. Effect of body mass index on recurrences in tamoxifen and anastrozole treated women: an exploratory analysis from the ATAC trial. J Clin Oncol. 2010;28(21):3411–5. https://doi.org/10.1200/JCO.2009.27.2021.CrossRefPubMed

37.

Ewertz M, Gray KP, Regan MM, Ejlertsen B, Price KN, Thürlimann B, et al. Obesity and risk of recurrence or death after adjuvant endocrine therapy with letrozole or tamoxifen in the breast international group 1–98 trial. J Clin Oncol. 2012;30(32):3967–75. https://doi.org/10.1200/JCO.2011.40.8666.CrossRefPubMedPubMedCentral

38.

Gelsomino L, Giordano C, Camera G, Sisci D, Marsico S, Campana A, et al. Leptin signaling contributes to aromatase inhibitor resistant breast cancer cell growth and activation of macrophages. Biomolecules. 2020;10(4):543. https://doi.org/10.3390/biom10040543.CrossRefPubMedPubMedCentral

39.

Bhardwaj P, Brown KA. Obese adipose tissue as a driver of breast cancer growth and development: update and emerging evidence. Front Oncol. 2021;30(11):638918. https://doi.org/10.3389/fonc.2021.638918.CrossRef

40.

Pfeiler G, Königsberg R, Hadji P, Fitzal F, Maroske M, Dressel-Ban G, et al. Impact of body mass index on estradiol depletion by aromatase inhibitors in postmenopausal women with early breast cancer. Br J Cancer. 2013;109(6):1522–7. https://doi.org/10.1038/bjc.2013.499.CrossRefPubMedPubMedCentral

41.

Folkerd EJ, Dixon JM, Renshaw L, A’Hern RP, Dowsett M. Suppression of plasma estrogen levels by letrozole and anastrozole is related to body mass index in patients with breast cancer. J Clin Oncol. 2012;30(24):2977–80. https://doi.org/10.1200/JCO.2012.42.0273.CrossRefPubMed

42.

Rosner GL, Hargis JB, Hollis DR, Budman DR, Weiss RB, Henderson IC, et al. Relationship between toxicity and obesity in women receiving adjuvant chemotherapy for breast cancer: results from cancer and leukemia group B study 8541. J Clin Oncol. 1996;14(11):3000–8. https://doi.org/10.1200/JCO.1996.14.11.3000.CrossRefPubMed

43.

Matikas A, Foukakis T, Moebus V, Greil R, Bengtsson NO, Steger GG, et al. Dose tailoring of adjuvant chemotherapy for breast cancer based on hematologic toxicities: further results from the prospective PANTHER study with focus on obese patients. Ann Oncol. 2019;30(1):109–14. https://doi.org/10.1093/annonc/mdy475.CrossRefPubMed

44.

Griggs JJ, Mangu PB, Anderson H, Balaban EP, Dignam JJ, Hryniuk WM, et al. Appropriate chemotherapy dosing for obese adult patients with cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2012;30(13):1553–61. https://doi.org/10.1200/JCO.2011.39.9436.CrossRefPubMed

45.

LeVee A, Mortimer J. The challenges of treating patients with breast cancer and obesity. Cancers (Basel). 2023;15(9):2526. https://doi.org/10.3390/cancers15092526.CrossRefPubMed

46.

•• Desmedt C, Fornili M, Clatot F, Demicheli R, De Bortoli D, Di Leo A, et al. Differential benefit of adjuvant docetaxel-based chemotherapy in patients with early breast cancer according to baseline body mass index. J Clin Oncol. 2020;38(25):2883–91. https://doi.org/10.1200/JCO.19.01771. This post hoc analysis of the adjuvant BIG 2-98 trial investigates the efficacy of docetaxel stratified by BMI, which demonstrated reduced DFS and OS in obese patients.CrossRefPubMed

47.

Ligorio F, Zambelli L, Fucà G, Lobefaro R, Santamaria M, Zattarin E, et al. Prognostic impact of body mass index (BMI) in HER2+ breast cancer treated with anti-HER2 therapies: from preclinical rationale to clinical implications. Ther Adv Med Oncol. 2022;8(14):17588359221079124. https://doi.org/10.1177/17588359221079123.CrossRef

48.

• Di Cosimo S, Porcu L, Agbor-Tarh D, Cinieri S, Franzoi MA, De Santis MC, et al. Effect of body mass index on response to neo-adjuvant therapy in HER2-positive breast cancer: an exploratory analysis of the NeoALTTO trial. Breast Cancer Res. 2020;22(1):115. https://doi.org/10.1186/s13058-020-01356-w. This post hoc analysis of the neoadjuvant NeoALTTO trial indicates an association between obesity and reduced pathologic complete response in patients with HER2+ BC.CrossRefPubMedPubMedCentral

49.

• Martel S, Lambertini M, Agbor-Tarh D, Ponde NF, Gombos A, Paterson V, et al. Body mass index and weight change in patients with HER2-positive early breast cancer: exploratory analysis of the ALTTO BIG 2–06 trial. J Natl Compr Canc Netw. 2021;19(2):181–9. https://doi.org/10.6004/jnccn.2020.7606. This post hoc analysis of the adjuvant ALTTO BIG2-06 trial examined the impact of BMI at BC diagnosis and weight change after 2 years on outcomes in patients with HER2+ early BC. Obesity and weight loss ≥5% was associated with significantly worse DFS.CrossRefPubMed

50.

Iyengar NM, Ligibel JA. Letter to the editor: lapatinib confounds post-hoc weight loss analysis in the ALTTO trial. J Natl Compr Canc Netw. 2022;20(1):xliv-xlv. https://doi.org/10.6004/jnccn.2021.7082.

51.

• Modi ND, Tan JQE, Rowland A, Koczwara B, Abuhelwa AY, Kichenadasse G, et al. The obesity paradox in early and advanced HER2 positive breast cancer: pooled analysis of clinical trial data. NPJ Breast Cancer. 2021;7(1):30. https://doi.org/10.1038/s41523-021-00241-9. This pooled analysis indicates an obesity paradox in patients in metastatic HER2+ breast cancer where higher BMI was associated with improved survival.CrossRefPubMedPubMedCentral

52.

Rock CL, Flatt SW, Byers TE, Colditz GA, Demark-Wahnefried W, Ganz PA, et al. Results of the exercise and nutrition to enhance recovery and good health for you (ENERGY) trial: a behavioral weight loss intervention in overweight or obese breast cancer survivors. J Clin Oncol. 2015;33(28):3169–76. https://doi.org/10.1200/JCO.2015.61.1095.

53.

Rock CL, Pande C, Flatt SW, Ying C, Pakiz B, Parker BA, et al. Favorable changes in serum estrogens and other biologic factors after weight loss in breast cancer survivors who are overweight or obese. Clin Breast Cancer. 2013;13(3):188–95. https://doi.org/10.1016/j.clbc.2012.12.002.CrossRefPubMedPubMedCentral

54.

Swisher AK, Abraham J, Bonner D, Gilleland D, Hobbs G, Kurian S, et al. Exercise and dietary advice intervention for survivors of triple-negative breast cancer: effects on body fat, physical function, quality of life, and adipokine profile. Support Care Cancer. 2015;23(10):2995–3003. https://doi.org/10.1007/s00520-015-2667-z.CrossRefPubMedPubMedCentral

55.

Demark-Wahnefried W, Jones LW, Snyder DC, Sloane RJ, Kimmick GG, Hughes DC, et al. Daughters and mothers against breast cancer (DAMES): main outcomes of a randomized controlled trial of weight loss in overweight mothers with breast cancer and their overweight daughters. Cancer. 2014;120(16):2522–34. https://doi.org/10.1002/cncr.28761.CrossRefPubMed

56.

Goodwin PJ, Segal RJ, Vallis M, Ligibel JA, Pond GR, Robidoux A, et al. The LISA randomized trial of a weight loss intervention in postmenopausal breast cancer. NPJ Breast Cancer. 2020;21(6):6. https://doi.org/10.1038/s41523-020-0149-z.CrossRef

57.

Demark-Wahnefried W, Morey MC, Sloane R, Snyder DC, Miller PE, Hartman TJ, et al. Reach out to enhance wellness home-based diet-exercise intervention promotes reproducible and sustainable long-term improvements in health behaviors, body weight, and physical functioning in older, overweight/obese cancer survivors. J Clin Oncol. 2012;30(19):2354–61. https://doi.org/10.1200/JCO.2011.40.0895.CrossRefPubMedPubMedCentral

58.

Harrigan M, Cartmel B, Loftfield E, Sanft T, Chagpar AB, Zhou Y, et al. Randomized trial comparing telephone versus in-person weight loss counseling on body composition and circulating biomarkers in women treated for breast cancer: the lifestyle, exercise, and nutrition (LEAN) study. J Clin Oncol. 2016;34(7):669–76. https://doi.org/10.1200/JCO.2015.61.6375.CrossRefPubMed

59.

Pierce JP, Natarajan L, Caan BJ, Parker BA, Greenberg ER, Flatt SW, et al. Influence of a diet very high in vegetables, fruit, and fiber and low in fat on prognosis following treatment for breast cancer: the women’s healthy eating and living (WHEL) randomized trial. JAMA. 2007;298(3):289–98. https://doi.org/10.1001/jama.298.3.289.CrossRefPubMedPubMedCentral

60.

Pakiz B, Flatt SW, Bardwell WA, Rock CL, Mills PJ. Effects of a weight loss intervention on body mass, fitness, and inflammatory biomarkers in overweight or obese breast cancer survivors. Int J Behav Med. 2011;18(4):333–41. https://doi.org/10.1007/s12529-010-9079-8.CrossRefPubMedPubMedCentral

61.

Sheppard VB, Hicks J, Makambi K, Hurtado-de-Mendoza A, Demark-Wahnefried W, Adams-Campbell L. The feasibility and acceptability of a diet and exercise trial in overweight and obese black breast cancer survivors: The stepping STONE study. Contemp Clin Trials. 2016;46:106–13. https://doi.org/10.1016/j.cct.2015.12.005.CrossRefPubMed

62.

Chlebowski RT, Blackburn GL, Thomson CA, Nixon DW, Shapiro A, Hoy MK, et al. Dietary fat reduction and breast cancer outcome: interim efficacy results from the women’s intervention nutrition study. J Natl Cancer Inst. 2006;98(24):1767–76. https://doi.org/10.1093/jnci/djj494.CrossRefPubMed

63.

Goodwin PJ, Segal RJ, Vallis M, Ligibel JA, Pond GR, Robidoux A, et al. Randomized trial of a telephone-based weight loss intervention in postmenopausal women with breast cancer receiving letrozole: the LISA trial. J Clin Oncol. 2014;32(21):2231–9.CrossRefPubMed

64.

Villarini A, Pasanisi P, Traina A, Mano MP, Bonanni B, Panico S, et al. Lifestyle and breast cancer recurrences: the DIANA-5 trial. Tumori J. 2012;98(1):1–18.CrossRef

65.

Bruno E, Krogh V, Gargano G, Grioni S, Bellegotti M, Venturelli E, et al. Adherence to dietary recommendations after one year of intervention in breast cancer women: the DIANA-5 trial. Nutrients. 2021;13(9):2990. https://doi.org/10.3390/nu13092990.CrossRefPubMedPubMedCentral

66.

Prevention of breast cancer recurrence through weight control, diet, and physical activity intervention (PREDICOP) [cited 2023 Sept 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT02035631

67.

Rack B, Andergassen U, Neugebauer J, Salmen J, Hepp P, Sommer H, et al. The German SUCCESS C study – the first European lifestyle study on breast cancer. Breast Care (Basel). 2010;5(6):395–400. https://doi.org/10.1159/000322677.CrossRefPubMed

68.

•• Ligibel JA, Ballman KV, McCall LM, Goodwin PJ, Weiss A, Delahanty L, et al. Effect of a telephone-based weight loss intervention (WLI) on weight at 12-months in women with early breast cancer: results from the breast cancer weight loss (BWEL) trial. J Clin Oncol. 2023;41(16_suppl):12001–12001. This study abstract presented at ASCO 2023 reports a telephone-based weight-loss intervention that induced significant, clinically meaningful weight loss in patients with stage II or III breast cancer with overweight or obesity. Longer follow-up is required to evaluate whether the intervention improves disease outcomes in this patient population.CrossRef

69.

Ligibel JA, Barry WT, Alfano CM, Hershman DL, Irwin ML, Neuhouser M, et al. The breast cancer weight loss (BWEL) trial: randomized phase III trial evaluating the role of weight loss in adjuvant treatment of overweight and obese women with early-stage breast cancer (Alliance A011401). J Clin Oncol. 2018;36(15_suppl):TPS598–TPS598.CrossRef

70.

Pierce JP. Diet and breast cancer prognosis: making sense of the Women’s Healthy Eating and Living and women’s intervention nutrition study trials. Curr Opin Obstet Gynecol. 2009;21(1):86–91. https://doi.org/10.1097/gco.0b013e32831da7f2.CrossRefPubMedPubMedCentral

71.

Iyengar NM, Jones LW. Development of exercise as interception therapy for cancer: a review. JAMA Oncol. 2019;5(11):1620–7.CrossRefPubMedPubMedCentral

72.

A study of the body’s response to exercise and a plant-based diet in overweight postmenopausal women with breast cancer [cited 2023 Sept 20]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT04298086

73.

Cejuela M, Martin-Castillo B, Menendez JA, Pernas S. Metformin and breast cancer: where are we now? Int J Mol Sci. 2022;23(5):2705. https://doi.org/10.3390/ijms23052705.CrossRefPubMedPubMedCentral

74.

• Bellerba F, Chatziioannou AC, Jasbi P, Robinot N, Keski-Rahkonen P, Trolat A, et al. Metabolomic profiles of metformin in breast cancer survivors: a pooled analysis of plasmas from two randomized placebo-controlled trials. J Transl Med. 2022;20(1):629. https://doi.org/10.1186/s12967-022-03809-6. This study investigated the metabolomic effects of metformin therapy in patients with BC and indicates changes in biochemical pathways implicated in cancer cell growth.CrossRefPubMedPubMedCentral

75.

Coyle C, Cafferty FH, Vale C, Langley RE. Metformin as an adjuvant treatment for cancer: a systematic review and meta-analysis. Ann Oncol. 2016;27(12):2184–95. https://doi.org/10.1093/annonc/mdw410.CrossRefPubMedPubMedCentral

76.

• El-Attar AA, Ibrahim OM, Alhassanin SA, Essa ES, Mostafa TM. Effect of metformin as an adjuvant therapy to letrozole on estradiol and other biomarkers involved in the pathogenesis of breast cancer in overweight and obese postmenopausal women: a pilot study. Eur J Clin Pharmacol. 2023;79(2):299–309. https://doi.org/10.1007/s00228-022-03444-6. This study investigated the effect of metformin on biomarkers associated with breast cancer recurrence and found improvement in prognostic biomarkers.CrossRefPubMed

77.

Patterson RE, Marinac CR, Sears DD, Kerr J, Hartman SJ, Cadmus-Bertram L, et al. The effects of metformin and weight loss on biomarkers associated with breast cancer outcomes. J Natl Cancer Inst. 2018Nov 1;110(11):1239–47. https://doi.org/10.1093/jnci/djy040.CrossRefPubMedPubMedCentral

78.

Sonnenblick A, Agbor-Tarh D, Bradbury I, Di Cosimo S, Azim HA Jr, Fumagalli D, et al. Impact of diabetes, insulin, and metformin use on the outcome of patients with human epidermal growth factor receptor 2-positive primary breast cancer: analysis from the ALTTO phase III randomized trial. J Clin Oncol. 2017;35(13):1421–9. https://doi.org/10.1200/JCO.2016.69.7722.CrossRefPubMedPubMedCentral

79.

•• Goodwin PJ, Chen BE, Gelmon KA, Whelan TJ, Ennis M, Lemieux J, et al. Effect of metformin vs placebo on invasive disease-free survival in patients with breast cancer: the MA.32 randomized clinical trial. JAMA. 2022;327(20):1963–73. https://doi.org/10.1001/jama.2022.6147. This definitive trial investigated the efficacy of adjuvant metformin versus placebo in patients with primary breast cancer. Addition of metformin to standard breast cancer treatment did not improve invasive disease-free survival.CrossRefPubMedPubMedCentral

80.

Gallagher EJ, Kase NG, Bickell NA, LeRoith D. Metformin and cancer: is this the end? Endocr Pract. 2022;28(8):832–4. https://doi.org/10.1016/j.eprac.2022.06.005.CrossRefPubMed

81.

Drucker DJ. Mechanisms of action and therapeutic application of glucagon-like peptide-1. Cell Metab. 2018;27(4):740–56. https://doi.org/10.1016/j.cmet.2018.03.001.CrossRefPubMed

82.

Pi-Sunyer X, Astrup A, Fujioka K, et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. N Engl J Med. 2015;373(1):11–22. https://doi.org/10.1056/NEJMoa1411892.CrossRefPubMed

83.

Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384(11):989–1002. https://doi.org/10.1056/NEJMoa2032183.CrossRefPubMed

84.

Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387(3):205–16. https://doi.org/10.1056/NEJMoa2206038.CrossRefPubMed

85.

Ligumsky H, Wolf I, Israeli S, et al. The peptide-hormone glucagon-like peptide-1 activates cAMP and inhibits growth of breast cancer cells. Breast Cancer Res Treat. 2012;132(2):449–61. https://doi.org/10.1007/s10549-011-1585-0.CrossRefPubMed

86.

Iwaya C, Nomiyama T, Komatsu S, et al. Exendin-4, a glucagonlike peptide-1 receptor agonist, attenuates breast cancer growth by inhibiting NF-κB activation. Endocrinology. 2017;158(12):4218–32. https://doi.org/10.1210/en.2017-00461.CrossRefPubMed

87.

Martin-Castillo B, Pernas S, Dorca J, Álvarez I, Martínez S, Pérez-Garcia JM, et al. A phase 2 trial of neoadjuvant metformin in combination with trastuzumab and chemotherapy in women with early HER2-positive breast cancer: the METTEN study. Oncotarget. 2018;9(86):35687–704. https://doi.org/10.18632/oncotarget.26286.CrossRefPubMedPubMedCentral

88.

•• Huang J, Tong Y, Hong J, Huang O, Wu J, He J, et al. Neoadjuvant docetaxel, epirubicin, and cyclophosphamide with or without metformin in breast cancer patients with metabolic abnormality: results from the randomized phase II NeoMET trial. Breast Cancer Res Treat. 2023;197(3):525–33. https://doi.org/10.1007/s10549-022-06821-y. This trial investigated the efficacy of adding metformin to neoadjuvant chemotherapy in early breast cancer. Addition of metformin did not significantly improve pathological complete response rates.CrossRefPubMed

89.

• Yee D, Isaacs C, Wolf DM, Yau C, Haluska P, Giridhar KV, et al. Ganitumab and metformin plus standard neoadjuvant therapy in stage 2/3 breast cancer. NPJ Breast Cancer. 2021;7(1):131. https://doi.org/10.1038/s41523-021-00337-2. This trial explores the efficacy of adding metformin and ganitumab to neoadjuvant chemotherapy in stage 2/3 breast cancer. Although an improved pathological complete response rate was observed, the trial did not meet the prespecified threshold for advancement to phase 3 testing.CrossRefPubMedPubMedCentral

90.

Topart P. Obesity surgery: which procedure should we choose and why? J Visc Surg. 2023;160(2S):S30–7. https://doi.org/10.1016/j.jviscsurg.2022.12.010.CrossRefPubMed

91.

Eisenberg D, Shikora SA, Aarts E, Aminian A, Angrisani L, Cohen RV, et al. 2022 American Society for Metabolic and Bariatric Surgery (ASMBS) and International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO): indications for metabolic and bariatric surgery. Surg Obes Relat Dis. 2022;18(12):1345–56. https://doi.org/10.1016/j.soard.2022.08.013.CrossRefPubMed

92.

Mackenzie H, Markar SR, Askari A, Faiz O, Hull M, Purkayastha S, et al. Obesity surgery and risk of cancer. Br J Surg. 2018;105(12):1650–7. https://doi.org/10.1002/bjs.10914.CrossRefPubMed

93.

•Doumouras AG, Lovrics O, Paterson JM, Sutradhar R, Paszat L, Sivapathasundaram B et al. Residual Risk of Breast Cancer After Bariatric Surgery. JAMA Surg. 2023;12:e230530. https://doi.org/10.1001/jamasurg.2023.0530. Epub ahead of print. In this matched cohort study, bariatric surgery was associated with a reduction in breast cancer risk.

94.

•• Aminian A, Wilson R, Al-Kurd A, Tu C, Milinovich A, Kroh M, et al. Association of bariatric surgery with cancer risk and mortality in adults with obesity. JAMA. 2022;327(24):2423–33. https://doi.org/10.1001/jama.2022.9009. The SPLENDID matched cohort study investigated time to incidence of obesity induced cancers in patients treated with and without bariatric surgery. Bariatric surgery was associated with a significantly lower incidence of obesity-associated cancers and cancer-related mortality.CrossRefPubMedPubMedCentral

95.

Wilson RB, Lathigara D, Kaushal D. Systematic review and meta-analysis of the impact of bariatric surgery on future cancer risk. Int J Mol Sci. 2023;24(7):6192. https://doi.org/10.3390/ijms24076192.CrossRefPubMedPubMedCentral

96.

Zhang S, Ikramuddin S, Beckwith HC, Sheka AC, Wirth KM, Blaes AH. The impact of bariatric surgery on breast cancer recurrence: case series and review of literature. Obes Surg. 2020;30(2):780–5. https://doi.org/10.1007/s11695-019-04099-6.CrossRefPubMedPubMedCentral

97.

BariaTric Surgery After Breast Cancer Treatment (BATS) [cited 2023 Sept 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT03946423

98.

Rothman KJ. BMI-related errors in the measurement of obesity. Int J Obes (Lond). 2008;32(Suppl 3):S56–9. https://doi.org/10.1038/ijo.2008.87.CrossRefPubMed

99.

Deurenberg P, Andreoli A, Borg P, Kukkonen-Harjula K, de Lorenzo A, van Marken Lichtenbelt WD, et al. The validity of predicted body fat percentage from body mass index and from impedance in samples of five European populations. Eur J Clin Nutr. 2001;55(11):973–9. https://doi.org/10.1038/sj.ejcn.1601254.CrossRefPubMed

100.

Ruderman NB, Schneider SH, Berchtold P. The, “metabolically-obese”, normal-weight individual. Am J Clin Nutr. 1981;34(8):1617–21. https://doi.org/10.1093/ajcn/34.8.1617.CrossRefPubMed

101.

Stefan N, Schick F, Häring HU. Causes, characteristics, and consequences of metabolically unhealthy normal weight in humans. Cell Metab. 2017;26(2):292–300. https://doi.org/10.1016/j.cmet.2017.07.008.CrossRefPubMed

102.

Franco LP, Morais CC, Cominetti C. Normal-weight obesity syndrome: diagnosis, prevalence, and clinical implications. Nutr Rev. 2016;74(9):558–70. https://doi.org/10.1093/nutrit/nuw019.CrossRefPubMed

103.

• Arthur RS, Dannenberg AJ, Kim M, Rohan TE. The association of body fat composition with risk of breast, endometrial, ovarian and colorectal cancers among normal weight participants in the UK Biobank. Br J Cancer. 2021;124(9):1592–605. This study reports an association between body fat levels and risk of several cancers in normal weight individuals; high body fat levels were associated with increased risk of obesity-related cancers in this normal weight population.CrossRefPubMedPubMedCentral

104.

Kim JW, Ahn ST, Oh MM, Moon DG, Han K, Park HS. Incidence of prostate cancer according to metabolic health status: a nationwide cohort study. J Korean Med Sci. 2019;34(6):e49–e49.CrossRefPubMedPubMedCentral

105.

Kabat GC, Kim MY, Stefanick M, Ho GYF, Lane DS, Odegaard AO, et al. Metabolic obesity phenotypes and risk of colorectal cancer in postmenopausal women. Int J Cancer. 2018;143(3):543–51.CrossRefPubMedPubMedCentral

106.

Liu B, Giffney HE, Arthur RS, Rohan TE, Dannenberg AJ. Cancer risk in normal weight individuals with metabolic obesity: a narrative review. Cancer Prev Res (Phila). 2021;14(5):509–20. https://doi.org/10.1158/1940-6207.CAPR-20-0633.CrossRefPubMed

107.

Iyengar NM, Arthur R, Manson JE, Chlebowski RT, Kroenke CH, Peterson L, et al. Association of body fat and risk of breast cancer in postmenopausal women with normal body mass index: a secondary analysis of a randomized clinical trial and observational study. JAMA Oncol. 2019;5(2):155–63. https://doi.org/10.1001/jamaoncol.2018.5327.CrossRefPubMed

108.

Park YM, White AJ, Nichols HB, O’Brien KM, Weinberg CR, Sandler DP. The association between metabolic health, obesity phenotype and the risk of breast cancer. Int J Cancer. 2017;140(12):2657–66. https://doi.org/10.1002/ijc.30684.CrossRefPubMedPubMedCentral

109.

Gunter MJ, Xie X, Xue X, Kabat GC, Rohan TE, Wassertheil-Smoller S, Ho GY, Wylie-Rosett J, Greco T, Yu H, Beasley J, Strickler HD. Breast cancer risk in metabolically healthy but overweight postmenopausal women. Cancer Res. 2015;75(2):270–4. https://doi.org/10.1158/0008-5472.CAN-14-2317.CrossRefPubMedPubMedCentral

110.

Ogundiran TO, Huo D, Adenipekun A, Campbell O, Oyesegun R, Akang E, Adebamowo C, Olopade OI. Body fat distribution and breast cancer risk: findings from the Nigerian breast cancer study. Cancer Causes Control. 2012;23(4):565–74. https://doi.org/10.1007/s10552-012-9916-y.CrossRefPubMedPubMedCentral

Titel: The Role of Obesity and Inflammation in Breast Cancer Recurrence
verfasst von: Sonya M. Chew
Bethina Liu
Sherry Shen
Neil M. Iyengar
Publikationsdatum: 18.05.2024
Verlag: Springer US
Erschienen in: Current Breast Cancer Reports
Print ISSN: 1943-4588
Elektronische ISSN: 1943-4596
DOI: https://doi.org/10.1007/s12609-024-00550-5

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

The Role of Obesity and Inflammation in Breast Cancer Recurrence

Abstract

Purpose of review

Recent Findings

Summary

Neu im Fachgebiet Onkologie

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

15% bedauern gewählte Blasenkrebs-Therapie

Erhöhtes Risiko fürs Herz unter Checkpointhemmer-Therapie

Costims – das nächste heiße Ding in der Krebstherapie?

Update Onkologie

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Purpose of review

Recent Findings

Summary

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Neu im Fachgebiet Onkologie

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

15% bedauern gewählte Blasenkrebs-Therapie

Erhöhtes Risiko fürs Herz unter Checkpointhemmer-Therapie

Costims – das nächste heiße Ding in der Krebstherapie?

Update Onkologie