Body Mass Index and Metabolic Phenotypes in Breast Cancer Risk: A Meta-Analysis and Systematic Review
DOI:
https://doi.org/10.6000/1929-6029.2024.13.09Keywords:
Obesity, metabolism, overweight, Breast Neoplasms (Source: MeSH NLM)Abstract
Introduction: Numerous studies have established that obesity, often assessed through body mass index (BMI), is one of the most significant risk factors for the development of breast cancer (BC). However, not all individuals with obesity have the same risk of developing BC and vice versa.
Objective: To determine the association between metabolic states and the risk of BC.
Materials: AS systematic review (SR) with a meta-analysis of cohort studies was conducted. The search was performed in four databases: PubMed/Medline, SCOPUS, Web of Science, and EMBASE. Metabolic states were classified as Metabolically Healthy Normal Weight (MHNW), Metabolically Unhealthy Normal Weight (MUNW), Metabolically Healthy Obesity (MHO), and Metabolically Unhealthy Obesity (MUO). Association measures were presented as hazard ratios (HR) with their 95% confidence intervals (CI95%).
Results: A total of four studies were evaluated. The meta-analysis found a statistically significant association between the development of BC and the MHO state (HR: 1.14; CI95% 1.02, 1.28) and MUO state (HR: 1.37; CI95% 1.16, 1.62) compared to individuals with MHNW. No association was found with the MUNW state.
Conclusions: The findings suggest that obesity, as determined by BMI, is significantly associated with an increased risk of BC, regardless of metabolic state. Additionally, metabolically unhealthy states, especially in obese individuals, appear to increase the risk of BC. Proposed mechanisms include systemic inflammation, metabolic dysfunction, and altered hormone production. These results have important public health implications, emphasizing the need for prevention strategies focused on obesity management and awareness of its associated BC risks.
References
Cancer today [Internet]. [citado el 11 de junio de 2023]. Disponible en: http://gco.iarc.fr/today/home
Rakha EA, Tan PH, Quinn C, Provenzano E, Shaaban AM, Deb R, et al. UK recommendations for HER2 assessment in breast cancer: an update. J Clin Pathol 2023; 76(4): 217-27. https://doi.org/10.1136/jcp-2022-208632 DOI: https://doi.org/10.1136/jcp-2022-208632
Cáncer de mama [Internet]. [citado el 11 de junio de 2023]. Disponible en: https://www.who.int/es/news-room/fact-sheets/detail/breast-cancer
Islami F, Goding Sauer A, Miller KD, Siegel RL, Fedewa SA, Jacobs EJ, et al. Proportion and number of cancer cases and deaths attributable to potentially modifiable risk factors in the United States. CA Cancer J Clin 2018; 68(1): 31-54. https://doi.org/10.3322/caac.21440 DOI: https://doi.org/10.3322/caac.21440
DeSantis CE, Miller KD, Goding Sauer A, Jemal A, Siegel RL. Cancer statistics for African Americans, 2019. CA Cancer J Clin 2019; 69(3): 211-33. https://doi.org/10.3322/caac.21555 DOI: https://doi.org/10.3322/caac.21555
Amadou A, Ferrari P, Muwonge R, Moskal A, Biessy C, Romieu I, et al. Overweight, obesity and risk of premenopausal breast cancer according to ethnicity: a systematic review and dose-response meta-analysis. Obes Rev 2013; 14(8): 665-78. https://doi.org/10.1111/obr.12028 DOI: https://doi.org/10.1111/obr.12028
Peruchet-Noray L, Dimou N, Sedlmeier AM, Fervers B, Romieu I, Viallon V, et al. Body Shape Phenotypes and Breast Cancer Risk: A Mendelian Randomization Analysis. Cancers (Basel) 2023; 15(4): 1296. https://doi.org/10.3390/cancers15041296 DOI: https://doi.org/10.3390/cancers15041296
Cheraghi Z, Poorolajal J, Hashem T, Esmailnasab N, Doosti Irani A. Effect of body mass index on breast cancer during premenopausal and postmenopausal periods: a meta-analysis. PLoS One 2012; 7(12): e51446. https://doi.org/10.1371/journal.pone.0051446 DOI: https://doi.org/10.1371/journal.pone.0051446
Park Y-MM, 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 DOI: https://doi.org/10.1002/ijc.30684
Kabat GC, Kim MY, Lee JS, Ho GY, Going SB, Beebe-Dimmer J, et al. Metabolic Obesity Phenotypes and Risk of Breast Cancer in Postmenopausal Women. Cancer Epidemiol Biomarkers Prev 2017; 26(12): 1730-5. https://doi.org/10.1158/1055-9965.EPI-17-0495 DOI: https://doi.org/10.1158/1055-9965.EPI-17-0495
Park B, Kim S, Kim H, Cha C, Chung MS. Associations between obesity, metabolic health, and the risk of breast cancer in East Asian women. Br J Cancer 2021; 125(12): 1718-25. https://doi.org/10.1038/s41416-021-01540-5 DOI: https://doi.org/10.1038/s41416-021-01540-5
Sun M, Fritz J, Häggström C, Bjørge T, Nagel G, Manjer J, et al. Metabolically (un)healthy obesity and risk of obesity-related cancers: a pooled study. J Natl Cancer Inst 2023; 115(4): 456-67. https://doi.org/10.1093/jnci/djad008 DOI: https://doi.org/10.1093/jnci/djad008
Wildman RP, Muntner P, Reynolds K, McGinn AP, Rajpathak S, Wylie-Rosett J, et al. The Obese Without Cardiometabolic Risk Factor Clustering and the Normal Weight With Cardiometabolic Risk Factor Clustering: Prevalence and Correlates of 2 Phenotypes Among the US Population (NHANES 1999-2004). Arch Intern Med 2008; 168(15): 1617-24. https://doi.org/10.1001/archinte.168.15.1617 DOI: https://doi.org/10.1001/archinte.168.15.1617
Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009; 6(7): e1000097. https://doi.org/10.1371/journal.pmed.1000097 DOI: https://doi.org/10.1371/journal.pmed.1000097
Ottawa Hospital Research Institute [Internet]. [citado el 11 de julio de 2022]. Disponible en: https://www.ohri.ca/programs/ clinical_epidemiology/oxford.asp
Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21(11): 1539-58. https://doi.org/10.1002/sim.1186 DOI: https://doi.org/10.1002/sim.1186
Cochrane Handbook for Systematic Reviews of Interventions [Internet]. [citado el 27 de noviembre de 2021]. Disponible en: https://training.cochrane.org/handbook
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA 2001; 285(19): 2486-97. https://doi.org/10.1001/jama.285.19.2486 DOI: https://doi.org/10.1001/jama.285.19.2486
Excess Weight and Breast Cancer: What’s the Risk? [Internet]. [citado el 17 de diciembre de 2023]. Disponible en: https://www.breastcancer.org/risk/risk-factors/being-overweight
Naaman SC, Shen S, Zeytinoglu M, Iyengar NM. Obesity and Breast Cancer Risk: The Oncogenic Implications of Metabolic Dysregulation. J Clin Endocrinol Metab 2022; 107(8): 2154-66. https://doi.org/10.1210/clinem/dgac241 DOI: https://doi.org/10.1210/clinem/dgac241
Seiler A, Chen MA, Brown RL, Fagundes CP. Obesity, Dietary Factors, Nutrition, and Breast Cancer Risk. Curr Breast Cancer Rep 2018; 10(1): 14-27. https://doi.org/10.1007/s12609-018-0264-0 DOI: https://doi.org/10.1007/s12609-018-0264-0
Zhang K, Chen L, Zheng H, Zeng Y. Cytokines secreted from adipose tissues mediate tumor proliferation and metastasis in triple negative breast cancer. BMC Cancer 2022; 22(1): 886. https://doi.org/10.1186/s12885-022-09959-6 DOI: https://doi.org/10.1186/s12885-022-09959-6
Hildebrandt X, Ibrahim M, Peltzer N. Cell death and inflammation during obesity: “Know my methods, WAT(son)”. Cell Death Differ 2023; 30(2): 279-92. https://doi.org/10.1038/s41418-022-01062-4 DOI: https://doi.org/10.1038/s41418-022-01062-4
Kern L, Mittenbühler MJ, Vesting AJ, Ostermann AL, Wunderlich CM, Wunderlich FT. Obesity-Induced TNFα and IL-6 Signaling: The Missing Link between Obesity and Inflammation-Driven Liver and Colorectal Cancers. Cancers (Basel) 2018; 11(1): 24. https://doi.org/10.3390/cancers11010024 DOI: https://doi.org/10.3390/cancers11010024
Gallagher EJ, LeRoith D. Hyperinsulinaemia in cancer. Nat Rev Cancer 2020; 20(11): 629-44. https://doi.org/10.1038/s41568-020-0295-5 DOI: https://doi.org/10.1038/s41568-020-0295-5
Zhang AMY, Wellberg EA, Kopp JL, Johnson JD. Hyperinsulinemia in Obesity, Inflammation, and Cancer. Diabetes Metab J 2021; 45(3): 285-311. https://doi.org/10.4093/dmj.2020.0250 DOI: https://doi.org/10.4093/dmj.2020.0250
Bhardwaj P, Brown KA. Obese Adipose Tissue as a Driver of Breast Cancer Growth and Development: Update and Emerging Evidence. Front Oncol 2021; 11: 638918. https://doi.org/10.3389/fonc.2021.638918 DOI: https://doi.org/10.3389/fonc.2021.638918
Mair KM, Gaw R, MacLean MR. Obesity, estrogens and adipose tissue dysfunction - implications for pulmonary arterial hypertension. Pulm Circ 2020; 10(3): 2045894020952019. https://doi.org/10.1177/2045894020952023 DOI: https://doi.org/10.1177/2045894020952023
Gérard C, Brown KA. Obesity and breast cancer - Role of estrogens and the molecular underpinnings of aromatase regulation in breast adipose tissue. Mol Cell Endocrinol 2018; 466: 15-30. https://doi.org/10.1016/j.mce.2017.09.014 DOI: https://doi.org/10.1016/j.mce.2017.09.014
Avagliano A, Ruocco MR, Aliotta F, Belviso I, Accurso A, Masone S, et al. Mitochondrial Flexibility of Breast Cancers: A Growth Advantage and a Therapeutic Opportunity. Cells 2019; 8(5): 401. https://doi.org/10.3390/cells8050401 DOI: https://doi.org/10.3390/cells8050401
Brown KA. Metabolic pathways in obesity-related breast cancer. Nat Rev Endocrinol 2021; 17(6): 350-63. https://doi.org/10.1038/s41574-021-00487-0 DOI: https://doi.org/10.1038/s41574-021-00487-0
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