Association between obesity and triple-negative breast cancer: a systematic qualitative review

Authors

DOI:

https://doi.org/10.29289/2594539420230035

Keywords:

obesity, breast neoplasm, triple negative breast cancer

Abstract

Introduction: The relation between obesity and triple-negative breast cancer (TNBC) is not totally elucidated. TNBC represents a heterogeneous group of aggressive growth neoplasms. The concepts related to the development of hormone receptor-positive tumors cannot be directly extended to this group. To evaluate the association between obesity and TNBC, considering as primary outcome the assessment of the incidence of this tumor subtype in this population and as secondary outcomes the specific pathophysiology, prognosis, and treatment in this context. Methods: This was a systematic review following the Preferred Reporting Items for Systematic reviews and Meta-Analyses — PRISMA statement. PubMed/MEDLINE and Cochrane were the databases used as primary paper sources. Inclusion according to titles and abstracts allowed a secondary selection by reference list revision. The final full-text review was done on the most opportune studies identified. Results: A total of 52 articles were included. Epidemiology: A higher frequency of obesity among TNBC patients compared to other subtypes and TNBC in obese women was observed in the literature. It is uncertain whether premenopausal status is an aggravating factor. Pathophysiology: Several studies identified the production of different factors by obese adipose tissue and their regulation of genes related to the expression of stem-like cell properties, mainly leptin, IL-6, and IL-8. Prognosis: Most studies pointed out that disease-free survival and overall survival are independent of body mass index. Treatment: Weight reduction showed no significant power in improving prognosis but may favor primary incidence prevention. Drugs based on obesity-related pathways are still in research, and various potential targets were raised. Conclusions: Obesity is a risk factor for TNBC. Obese-related inflammatory cytokines may contribute to tumor development. Once TNBC is established, the prognosis does not differ according to initial body mass index changes. No target drug for obesity-related tumorigenic pathways is currently available for clinical use.

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References

1. Cleary MP, Grossmann ME. Minireview: obesity and breast cancer: the estrogen connection. Endocrinology. 2009;150(6):2537-42. https://doi.org/10.1210/en.2009-0070

2. Foulkes WD, Smith IE, Reis-Filho JS. Triple-negative breast cancer. N Engl J Med. 2010;363(20):1938-48. https://doi.org/10.1056/NEJMra1001389

3. Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535. https://doi.org/10.1136/bmj.b2535

4. Millikan RC, Newman B, Tse CK, Moorman PG, Conway K, Dressler LG, et al. Epidemiology of basal-like breast cancer. Breast Cancer Res Treat. 2008;109(1):123-39. https://doi.org/10.1007/s10549-007-9632-6

5. Vona-Davis L, Rose DP, Hazard H, Howard-McNatt M, Adkins F, Partin J, et al. Triple-negative breast cancer and obesity in a rural Appalachian population. Cancer Epidemiol Biomarkers Prev. 2008;17(12):3319-24. https://doi.org/10.1158/1055-9965.EPI-08-0544

6. Trivers KF, Lund MJ, Porter PL, Liff JM, Flagg EW, Coates RJ, et al. The epidemiology of triple-negative breast cancer, including race. Cancer Causes Control. 2009;20(7):1071-82. https://doi.org/10.1007/s10552-009-9331-1

7. Kwan ML, Kushi LH, Weltzien E, Maring B, Kutner SE, Fulton RS, et al. Epidemiology of breast cancer subtypes in two prospective cohort studies of breast cancer survivors. Breast Cancer Res. 2009;11(3): R31. https://doi.org/10.1186/bcr2261

8. Yang XR, Chang-Claude J, Goode EL, Couch FJ, Nevanlinna H, Milne RL, et al. Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium studies. J Natl Cancer Inst. 2011;103(3):250-63. https://doi.org/10.1093/jnci/djq526

9. Gaudet MM, Press MF, Haile RW, Lynch CF, Glaser SL, Schildkraut J, et al. Risk factors by molecular subtypes of breast cancer across a population-based study of women 56 years or younger. Breast Cancer Res Treat. 2011;130(2):587-97. https://doi.org/10.1007/s10549-011-1616-x

10. Pierobon M, Frankenfeld CL. Obesity as a risk factor for triple-negative breast cancers: a systematic review and meta-analysis. Breast Cancer Res Treat. 2013;137(1):307-14. https://doi.org/10.1007/s10549-012-2339-3

11. Chen L, Cook LS, Tang MTC, Porter PL, Hill DA, Wiggins CL, et al. Body mass index and risk of luminal, HER2-overexpressing, and triple negative breast cancer. Breast Cancer Res Treat. 2016;157(3):545-54. https://doi.org/10.1007/s10549-016-3825-9

12. Picon-Ruiz M, Morata-Tarifa C, Valle-Goffin JJ, Friedman ER, Slingerland JM. Obesity and adverse breast cancer risk and outcome: mechanistic insights and strategies for intervention. CA Cancer J Clin. 2017;67(5):378-97. https://doi.org/10.3322/caac.21405

13. Somali I, Ustaoglu BY, Tarhan MO, Yigit SC, Demir L, Ellidokuz H, et al. Clinicopathologic and demographic evaluation of triple- negative breast cancer patients among a Turkish patient population: a single center experience. Asian Pac J Cancer Prev. 2013;14(10):6013-7. https://doi.org/10.7314/apjcp.2013.14.10.6013

14. Enger SM, Ross RK, Paganini-Hill A, Carpenter CL, Bernstein L. Body size, physical activity, and breast cancer hormone receptor status: results from two case-control studies. Cancer Epidemiol Biomarkers Prev. 2000;9(7):681-7. PMID: 10919738.

15. Maiti B, Kundranda MN, Spiro TP, Daw HA. The association of metabolic syndrome with triple-negative breast cancer. Breast Cancer Res Treat. 2010;121(2):479-83. https://doi.org/10.1007/s10549-009-0591-y

16. Siddharth S, Sharma D. Racial disparity and triple-negative breast cancer in african-american women: a multifaceted affair between obesity, biology, and socioeconomic determinants. Cancers (Basel). 2018;10(12):514. https://doi.org/10.3390/cancers10120514

17. Zheng Q, Banaszak L, Fracci S, Basali D, Dunlap SM, Hursting SD, et al. Leptin receptor maintains cancer stem-like properties in triple negative breast cancer cells. Endocr Relat Cancer. 2013;20(6):797-808. https://doi.org/10.1530/ERC-13-0329

18. Sultana R, Kataki AC, Borthakur BB, Basumatary TK, Bose S. Imbalance in leptin-adiponectin levels and leptin receptor expression as chief contributors to triple negative breast cancer progression in Northeast India. Gene. 2017;621:51-8. https://doi.org/10.1016/j.gene.2017.04.021

19. Kolb R, Zhang W. Obesity and breast cancer: a case of inflamed adipose tissue. Cancers (Basel). 2020;12(6):1686. https://doi.org/10.3390/cancers12061686

20. Dietze EC, Chavez TA, Seewaldt VL. Obesity and triple-negative breast cancer: disparities, controversies, and biology. Am J Pathol. 2018;188(2):280-90. https://doi.org/10.1016/j.ajpath.2017.09.018

21. Tiwari P, Blank A, Cui C, Schoenfelt KQ, Zhou G, Xu Y, et al. Metabolically activated adipose tissue macrophages link obesity to triple-negative breast cancer. J Exp Med. 2019;216(6):1345-58. https://doi.org/10.1084/jem.20181616

22. Tian W, Wang L, Yuan L, Duan W, Zhao W, Wang S, et al. A prognostic risk model for patients with triple negative breast cancer based on stromal natural killer cells, tumor-associated macrophages and growth-arrest specific protein 6. Cancer Sci. 2016;107(7):882-9. https://doi.org/10.1111/cas.12964

23. Laue T, Wrann CD, Hoffmann-Castendiek B, Pietsch D, Hübner L, Kielstein H. Altered NK cell function in obese healthy humans. BMC Obes. 2015;2:1. https://doi.org/10.1186/s40608-014-0033-1

24. Naik A, Monjazeb AM, Decock J. The obesity paradox in cancer, tumor immunology, and immunotherapy: potential therapeutic implications in triple negative breast cancer. Front Immunol. 2019;10:1940. https://doi.org/10.3389/fimmu.2019.01940

25. Teslow EA, Mitrea C, Bao B, Mohammad RM, Polin LA, Dyson G, et al. Obesity-induced MBD2_v2 expression promotes tumor-initiating triple-negative breast cancer stem cells. Mol Oncol. 2019;13(4):894-908. https://doi.org/10.1002/1878-0261.12444

26. Sabol RA, Bowles AC, Côté A, Wise R, O'Donnell B, Matossian MD, et al. Leptin produced by obesity-altered adipose stem cells promotes metastasis but not tumorigenesis of triple-negative breast cancer in orthotopic xenograft and patient-derived xenograft models. Breast Cancer Res. 2019;21(1):67. https://doi.org/10.1186/s13058-019-1153-9

27. D'Esposito V, Liguoro D, Ambrosio MR, Collina F, Cantile M, Spinelli R, et al. Adipose microenvironment promotes triple negative breast cancer cell invasiveness and dissemination by producing CCL5. Oncotarget. 2016;7(17):24495-509. https://doi.org/10.18632/oncotarget.8336

28. Ewertz M, Jensen MB, Gunnarsdóttir KA, 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

29. Mei L, He L, Song Y, Lv Y, Zhang L, Hao F, et al. Association between obesity with disease-free survival and overall survival in triple-negative breast cancer: a meta-analysis. Medicine (Baltimore). 2018;97(19):e0719. https://doi.org/10.1097/MD.0000000000010719

30. Ademuyiwa FO, Groman A, O'Connor T, Ambrosone C, Watroba N, Edge SB. Impact of body mass index on clinical outcomes in triple-negative breast cancer. Cancer. 2011;117(18):4132-40. https://doi.org/10.1002/cncr.26019

31. Dawood S, Lei X, Litton JK, Buchholz TA, Hortobagyi GN, Gonzalez-Angulo AM. Impact of body mass index on survival outcome among women with early stage triple-negative breast cancer. Clin Breast Cancer. 2012;12(5):364-72. https://doi.org/10.1016/j.clbc.2012.07.013

32. Mowad R, Chu QD, Li BDL, Burton GV, Ampil FL, Kim RH. Does obesity have an effect on outcomes in triple-negative breast cancer? J Surg Res. 2013;184(1):253-59. https://doi.org/10.1016/j.jss.2013.05.037

33. Tait S, Pacheco JM, Gao F, Bumb C, Ellis MJ, Ma CX. Body mass index, diabetes, and triple-negative breast cancer prognosis. Breast Cancer Res Treat. 2014;146(1):189-97. https://doi.org/10.1007/s10549-014-3002-y

34. Schmidt G, Schneider C, Gerlinger C, Endrikat J, Gabriel L, Ströder R, et al. Impact of body mass index, smoking habit, alcohol consumption, physical activity and parity on disease course of women with triple-negative breast cancer. Arch Gynecol Obstet. 2020;301(2):603-9. https://doi.org/10.1007/s00404-019-05413-4

35. Turkoz FP, Solak M, Petekkaya I, Keskin O, Kertmen N, Sarici F, et al. The prognostic impact of obesity on molecular subtypes of breast cancer in premenopausal women. J BUON. 2013;18(2):335-41. PMID: 23818343.

36. Loi S, Milne RL, Friedlander ML, McCredie MRE, Giles GG, Hopper JL, et al. Obesity and outcomes in premenopausal and postmenopausal breast cancer. Cancer Epidemiol Biomarkers Prev. 2005;14(7):1686-91. https://doi.org/10.1158/1055-9965.EPI-05-0042

37. Hao S, Liu Y, Yu KD, Chen S, Yang WT, Shao ZM. Overweight as a prognostic factor for triple-negative breast cancers in chinese women. PLoS One. 2015;10(6):e0129741. https://doi.org/10.1371/journal.pone.0129741

38. Bao PP, Cai H, Peng P, Gu K, Su Y, Shu XO, et al. Body mass index and weight change in relation to triple-negative breast cancer survival. Cancer Causes Control. 2016;27(2):229-36. https://doi.org/10.1007/s10552-015-0700-7

39. Al Jarroudi O, Abda N, Seddik Y, Brahmi SA, Afqir S. Overweight: is it a prognostic factor in women with triple-negative breast cancer? Asian Pac J Cancer Prev. 2017;18(6):1519-23. https://doi.org/10.22034/APJCP.2017.18.6.1519

40. Choi Y, Park SK, Ahn KJ, Cho H, Kim TH, Yoon HK, et al. Being overweight or obese increases the risk of progression in triple-negative breast cancer after surgical resection. J Korean Med Sci. 2016;31(6):886-91. https://doi.org/10.3346/jkms.2016.31.6.886

41. Chen HL, Ding A, Wang ML. Impact of central obesity on prognostic outcome of triple negative breast cancer in Chinese women. Springerplus. 2016;5:594. https://doi.org/10.1186/s40064-016-2200-y

42. Maehle BO, Tretli S. Pre-morbid body-mass-index in breast cancer: reversed effect on survival in hormone receptor negative patients. Breast Cancer Res Treat. 1996;41(2):123-30. https://doi.org/10.1007/BF01807157

43. Eliassen AH, Colditz GA, Rosner B, Willett WC, Hankinson SE. Adult weight change and risk of postmenopausal breast cancer. JAMA. 2006;296(2):193-201. https://doi.org/10.1001/jama.296.2.193

44. Sundaram S, Le TL, Essaid L, Freemerman AJ, Huang MJ, Galanko JA, et al. Weight loss reversed obesity-induced HGF/c-Met pathway and basal-like breast cancer progression. Front Oncol. 2014;4:175. https://doi.org/10.3389/fonc.2014.00175

45. Qin Y, Sundaram S, Essaid L, Chen X, Miller SM, Yan F, et al. Weight loss reduces basal-like breast cancer through kinome reprogramming. Cancer Cell Int. 2016;16:26. https://doi.org/10.1186/s12935-016-0300-y

46. Bao J, Borja N, Rao M, Huth J, Leitch AM, Rivers A, et al. Impact of weight change during neoadjuvant chemotherapy on pathologic response in triple-negative breast cancer. Cancer Med. 2015;4(4):500-6. https://doi.org/10.1002/cam4.388

47. Wang T, Fahrmann JF, Lee H, Li YJ, Tripathi SC, Yue C, et al. JAK/STAT3-regulated fatty acid β-oxidation is critical for breast cancer stem cell self-renewal and chemoresistance. Cell Metab. 2018;27(1):136-50.e5. https://doi.org/10.1016/j.cmet.2017.11.001

48. Otvos Jr L, Kovalszky I, Riolfi M, Ferla R, Olah J, Sztodola A, et al. Efficacy of a leptin receptor antagonist peptide in a mouse model of triple-negative breast cancer. Eur J Cancer. 2011;47(10):1578-84. https://doi.org/10.1016/j.ejca.2011.01.018

49. Gourgue F, Mignion L, Van Hul M, Dehaen N, Bastien E, Payen V, et al. Obesity and triple-negative-breast-cancer: Is apelin a new key target? J Cell Mol Med. 2020;24(17):10233-44. https://doi.org/10.1111/jcmm.15639

50. Mamidi TKK, Wu J, Tchounwou PB, Miele L, Hicks C. whole genome transcriptome analysis of the association between obesity and triple-negative breast cancer in caucasian women. Int J Environ Res Public Health. 2018;15(11):2338. https://doi.org/10.3390/ijerph15112338

51. Potischman N, Swanson CA, Siiteri P, Hoover RN. Reversal of relation between body mass and endogenous estrogen concentrations with menopausal status. J Natl Cancer Inst. 1996;88(11):756-8. https://doi.org/10.1093/jnci/88.11.756

52. Sun H, Zou J, Chen L, Zu X, Wen G, Zhong J. Triple-negative breast cancer and its association with obesity. Mol Clin Oncol. 2017;7(6):935-42. https://doi.org/10.3892/mco.2017.1429

53. Irwin ML, McTiernan A, Manson JE, Thomson CA, Sternfeld B, Stefanick ML, et al. Physical activity and survival in postmenopausal women with breast cancer: results from the women's health initiative. Cancer Prev Res (Phila). 2011;4(4):522-9. https://doi.org/10.1158/1940-6207.CAPR-10-0295

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Published

2024-10-11

How to Cite

Iervolino, L. L., de Moraes, S. R., Filassi, J. R., Baracat, E. C., & Masili-Oku, S. (2024). Association between obesity and triple-negative breast cancer: a systematic qualitative review. Mastology, 34. https://doi.org/10.29289/2594539420230035

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Review Articles