Mechanistic Targets and Nutritionally Relevant Intervention Strategies to Break Obesity-Breast Cancer Links

Ximena M Bustamante-Marin, Jenna L Merlino, Emily Devericks, Meredith S Carson, Stephen D Hursting, Delisha A Stewart, Ximena M Bustamante-Marin, Jenna L Merlino, Emily Devericks, Meredith S Carson, Stephen D Hursting, Delisha A Stewart

Abstract

The worldwide prevalence of overweight and obesity has tripled since 1975. In the United States, the percentage of adults who are obese exceeds 42.5%. Individuals with obesity often display multiple metabolic perturbations, such as insulin resistance and persistent inflammation, which can suppress the immune system. These alterations in homeostatic mechanisms underlie the clinical parameters of metabolic syndrome, an established risk factor for many cancers, including breast cancer. Within the growth-promoting, proinflammatory milieu of the obese state, crosstalk between adipocytes, immune cells and breast epithelial cells occurs via obesity-associated hormones, angiogenic factors, cytokines, and other mediators that can enhance breast cancer risk and/or progression. This review synthesizes evidence on the biological mechanisms underlying obesity-breast cancer links, with emphasis on emerging mechanism-based interventions in the context of nutrition, using modifiable elements of diet alone or paired with physical activity, to reduce the burden of obesity on breast cancer.

Keywords: breast cancer; hormone signaling; immunosuppression; inflammation; metabolism; nutrition; obesity.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Bustamante-Marin, Merlino, Devericks, Carson, Hursting and Stewart.

Figures

Figure 1
Figure 1
Mechanisms linking obesity with breast cancer development and intervention strategies to break Obesity-Breast Cancer Links. Increased energy intake and low physical activity results in obesity. Excess adiposity causes systemic changes, such as increased circulating levels of insulin/IGF-1, aromatase activity, estrogen production, and leptin:adiponectin ratio. Local changes due to the hyperplasia and hypertrophy of adipocytes, leads to a pro-inflammatory response promoting the secretion of cytokines and inflammatory molecules. These systemic and local changes activate key signaling pathways (PI3K/AKT/mTOR, RAS/RAF/MAPK, and JAK/STAT). The complex interplay among all of these alterations generates a microenvironment favorable for breast epithelial cell transformation and increase breast cancer risk and progression. Dysfunctional adipocytes, distant and present within the tumor microenvironment, produce high levels of leptin that contributes to chronic inflammation and BC progression. Obesity promotes cell proliferation, migration and invasion, epithelial-mesenchymal transition (EMT), angiogenesis and recruitment of immune cells. Obesity increases myofibroblast content, which stiffens the extracellular matrix (ECM) and enhances cancer cell growth. All these effects stimulate the entry of invasive cells into the circulation and the subsequent metastatic colonization of distant organs, such as bone, lung, liver and brain. Nutritional interventions, such as calorie restricted diets with balanced protein content and intermittent fasting can break the obesity-BC links, the benefits of the dietary interventions can be further improved by increasing daily physical activity.

References

    1. Ford NA, Devlin KL, Lashinger LM, Hursting SD. Deconvoluting the Obesity and Breast Cancer Link: Secretome, Soil and Seed Interactions. J Mammary Gland Biol Neoplasia (2013) 18(3):267–75. 10.1007/s10911-013-9301-9
    1. WHO . Obesity and Overweight 2020. Geneva: World Health Organization; (2020). Available at: .
    1. 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. 10.1016/j.mce.2017.09.014
    1. Kelly T, Yang W, Chen CS, Reynolds K, He J. Global burden of obesity in 2005 and projections to 2030. Int J Obes (2008) 32(9):1431–7. 10.1038/ijo.2008.102
    1. Center for Disease Control and Prevention (CDC) HW . Nutrition, and Physical Activity. The Health Effects of Overweight and Obesity (2020) Atlanta, GA. Available at: .
    1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin (2018) 68(6):394–424. 10.3322/caac.21492
    1. Herschkowitz JI, Simin K, Weigman VJ, Mikaelian I, Usary J, Hu Z, et al. . Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors. Genome Biol (2007) 8(5):R76. 10.1186/gb-2007-8-5-r76
    1. Harbeck N, Penault-Llorca F, Cortes J, Gnant M, Houssami N, Poortmans P, et al. . Breast cancer. Nat Rev Dis Primers (2019) 5(1):66. 10.1038/s41572-019-0111-2
    1. Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. . Molecular portraits of human breast tumours. Nature (2000) 406(6797):747–52. 10.1038/35021093
    1. Shiovitz S, Korde LA. Genetics of breast cancer: a topic in evolution. Ann Oncol: Off J Eur Soc Med Oncol (2015) 26(7):1291–9. 10.1093/annonc/mdv022
    1. Danaei G, Vander Hoorn S, Lopez AD, Murray CJ, Ezzati M. Causes of cancer in the world: comparative risk assessment of nine behavioural and environmental risk factors. Lancet (London England) (2005) 366(9499):1784–93. 10.1016/s0140-6736(05)67725-2
    1. Rose DP, Vona-Davis L. Interaction between menopausal status and obesity in affecting breast cancer risk. Maturitas (2010) 66(1):33–8. 10.1016/j.maturitas.2010.01.019
    1. Agurs-Collins T, Ross SA, Dunn BK. The Many Faces of Obesity and Its Influence on Breast Cancer Risk. Front Oncol (2019) 9:765. 10.3389/fonc.2019.00765
    1. Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet (London England) (2008) 371(9612):569–78. 10.1016/s0140-6736(08)60269-x
    1. Suzuki R, Orsini N, Saji S, Key TJ, Wolk A. Body weight and incidence of breast cancer defined by estrogen and progesterone receptor status–a meta-analysis. Int J Cancer (2009) 124(3):698–712. 10.1002/ijc.23943
    1. Dietze EC, Chavez TA, Seewaldt VL. Obesity and Triple-Negative Breast Cancer: Disparities, Controversies, and Biology. Am J Pathol (2018) 188(2):280–90. 10.1016/j.ajpath.2017.09.018
    1. Bandera EV, Maskarinec G, Romieu I, John EM. Racial and ethnic disparities in the impact of obesity on breast cancer risk and survival: a global perspective. Adv Nutr (Bethesda Md) (2015) 6(6):803–19. 10.3945/an.115.009647
    1. Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K, et al. . Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. Jama (2006) 295(21):2492–502. 10.1001/jama.295.21.2492
    1. Santa-Maria CA, Yan J, Xie X-J, Euhus DM. Aggressive estrogen-receptor-positive breast cancer arising in patients with elevated body mass index. Int J Clin Oncol (2015) 20(2):317–23. 10.1007/s10147-014-0712-4
    1. Chan DS, Norat T. Obesity and breast cancer: not only a risk factor of the disease. Curr Treat Options Oncol (2015) 16(5):22. 10.1007/s11864-015-0341-9
    1. Argolo DF, Hudis CA, Iyengar NM. The Impact of Obesity on Breast Cancer. Curr Oncol Rep (2018) 20(6):47. 10.1007/s11912-018-0688-8
    1. Lee K, Kruper L, Dieli-Conwright CM, Mortimer JE. The Impact of Obesity on Breast Cancer Diagnosis and Treatment. Curr Oncol Rep (2019) 21(5):41–. 10.1007/s11912-019-0787-1
    1. Rossi EL, de Angel RE, Bowers LW, Khatib SA, Smith LA, Van Buren E, et al. . Obesity-Associated Alterations in Inflammation, Epigenetics, and Mammary Tumor Growth Persist in Formerly Obese Mice. Cancer Prev Res (Phila) (2016) 9(5):339–48. 10.1158/1940-6207.CAPR-15-0348
    1. Goodwin PJ, Ennis M, Pritchard KI, Trudeau ME, Koo J, Taylor SK, et al. . Insulin- and Obesity-Related Variables in Early-Stage Breast Cancer: Correlations and Time Course of Prognostic Associations. J Clin Oncol (2012) 30(2):164–71. 10.1200/JCO.2011.36.2723
    1. Haywood NJ, Slater TA, Matthews CJ, Wheatcroft SB. The insulin like growth factor and binding protein family: Novel therapeutic targets in obesity & diabetes. Mol Metab (2019) 19:86–96. 10.1016/j.molmet.2018.10.008
    1. Cheng T-YD, Omilian AR, Yao S, Sanchez PV, Polk LZ, Zhang W, et al. . Body fatness and mTOR pathway activation of breast cancer in the Women’s Circle of Health Study. NPJ Breast Cancer (2020) 6:45–. 10.1038/s41523-020-00187-4
    1. Allard JB, Duan C. IGF-Binding Proteins: Why Do They Exist and Why Are There So Many? Front Endocrinol (Lausanne) (2018) 9:117. 10.3389/fendo.2018.00117
    1. Engin A. Obesity-associated Breast Cancer: Analysis of risk factors. In: Engin AB, Engin A, editors. Obesity and Lipotoxicity. Cham: Springer International Publishing; (2017). p. 571–606.
    1. Bowers LW, Cavazos DA, Maximo IX, Brenner AJ, Hursting SD, deGraffenried LA. Obesity enhances nongenomic estrogen receptor crosstalk with the PI3K/Akt and MAPK pathways to promote in vitro measures of breast cancer progression. Breast Cancer Res: BCR (2013) 15(4):R59. 10.1186/bcr3453
    1. Giovannucci E, Harlan DM, Archer MC, Bergenstal RM, Gapstur SM, Habel LA, et al. . Diabetes and cancer: a consensus report. Diabetes Care (2010) 33(7):1674–85. 10.2337/dc10-0666
    1. Dankner R, Shanik MH, Keinan-Boker L, Cohen C, Chetrit A. Effect of elevated basal insulin on cancer incidence and mortality in cancer incident patients: the Israel GOH 29-year follow-up study. Diabetes Care (2012) 35(7):1538–43. 10.2337/dc11-1513
    1. Hemkens LG, Grouven U, Bender R, Günster C, Gutschmidt S, Selke GW, et al. . Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues: a cohort study. Diabetologia (2009) 52(9):1732–44. 10.1007/s00125-009-1418-4
    1. Nam S, Park S, Park HS, Kim S, Kim JY, Kim SI. Association Between Insulin Resistance and Luminal B Subtype Breast Cancer in Postmenopausal Women. Medicine (2016) 95(9):e2825. 10.1097/MD.0000000000002825
    1. Key T, Appleby P, Barnes I, Reeves G. Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst (2002) 94(8):606–16. 10.1093/jnci/94.8.606
    1. Bulun SE, Chen D, Moy I, Brooks DC, Zhao H. Aromatase, breast cancer and obesity: a complex interaction. Trends Endocrinol Metab (2012) 23(2):83–9. 10.1016/j.tem.2011.10.003
    1. Cleary MP, Grossmann ME. Minireview: Obesity and breast cancer: the estrogen connection. Endocrinology (2009) 150(6):2537–42. 10.1210/en.2009-0070
    1. Ahn J, Schatzkin A, Lacey JV Jr., Albanes D, Ballard-Barbash R, Adams KF, et al. . Adiposity, adult weight change, and postmenopausal breast cancer risk. Arch Internal Med (2007) 167(19):2091–102. 10.1001/archinte.167.19.2091
    1. Han YM, Kang GM, Byun K, Ko HW, Kim J, Shin M-S, et al. . Leptin-promoted cilia assembly is critical for normal energy balance. J Clin Invest (2014) 124(5):2193–7. 10.1172/JCI69395
    1. Vaisse C, Reiter JF, Berbari NF. Cilia and Obesity. Cold Spring Harbor Perspect Biol (2017) 9(7):a028217. 10.1101/cshperspect.a028217
    1. Lee JM, Kim SR, Yoo SJ, Hong OK, Son HS, Chang SA. The relationship between adipokines, metabolic parameters and insulin resistance in patients with metabolic syndrome and type 2 diabetes. J Int Med Res (2009) 37(6):1803–12. 10.1177/147323000903700616
    1. Ozenoglu A, Balci H, Ugurlu S, Caglar E, Uzun H, Sarkis C, et al. . The relationships of leptin, adiponectin levels and paraoxonase activity with metabolic and cardiovascular risk factors in females treated with psychiatric drugs. Clinics (Sao Paulo Brazil) (2008) 63(5):651–60. 10.1590/s1807-59322008000500014
    1. Frühbeck G, Catalán V, Rodríguez A, Gómez-Ambrosi J. Adiponectin-leptin ratio: A promising index to estimate adipose tissue dysfunction. Relation with obesity-associated cardiometabolic risk. Adipocyte (2018) 7(1):57–62. 10.1080/21623945.2017.1402151
    1. Mullen M, Gonzalez-Perez RR. Leptin-Induced JAK/STAT Signaling and Cancer Growth. Vaccines (Basel) (2016) 4(3):26. 10.3390/vaccines4030026
    1. Pérez-Pérez A, Vilariño-García T, Fernández-Riejos P, Martín-González J, Segura-Egea JJ, Sánchez-Margalet V. Role of leptin as a link between metabolism and the immune system. Cytokine Growth Fact Rev (2017) 35:71–84. 10.1016/j.cytogfr.2017.03.001
    1. Ollberding NJ, Kim Y, Shvetsov YB, Wilkens LR, Franke AA, Cooney RV, et al. . Prediagnostic leptin, adiponectin, C-reactive protein, and the risk of postmenopausal breast cancer. Cancer Prev Res (Phila) (2013) 6(3):188–95. 10.1158/1940-6207.CAPR-12-0374
    1. Nyasani E, Munir I, Perez M, Payne K, Khan S. Linking obesity-induced leptin-signaling pathways to common endocrine-related cancers in women. Endocrine (2019) 63(1):3–17. 10.1007/s12020-018-1748-4
    1. Dunlap SM, Chiao LJ, Nogueira L, Usary J, Perou CM, Varticovski L, et al. . Dietary energy balance modulates epithelial-to-mesenchymal transition and tumor progression in murine claudin-low and basal-like mammary tumor models. Cancer Prev Res (Phila) (2012) 5(7):930–42. 10.1158/1940-6207.CAPR-12-0034
    1. Dallal CM, Brinton LA, Matthews CE, Pfeiffer RM, Hartman TJ, Lissowska J, et al. . Association of Active and Sedentary Behaviors with Postmenopausal Estrogen Metabolism. Med Sci Sports Exerc (2016) 48(3):439–48. 10.1249/MSS.0000000000000790
    1. Oh H, Arem H, Matthews CE, Wentzensen N, Reding KW, Brinton LA, et al. . Sitting, physical activity, and serum oestrogen metabolism in postmenopausal women: the Women’s Health Initiative Observational Study. Br J Cancer (2017) 117(7):1070–8. 10.1038/bjc.2017.268
    1. Pizot C, Boniol M, Mullie P, Koechlin A, Boniol M, Boyle P, et al. . Physical activity, hormone replacement therapy and breast cancer risk: A meta-analysis of prospective studies. Eur J Cancer (Oxford England: 1990) (2016) 52:138–54. 10.1016/j.ejca.2015.10.063
    1. Cox CE. Role of Physical Activity for Weight Loss and Weight Maintenance. Diabetes Spectr (2017) 30(3):157–60. 10.2337/ds17-0013
    1. National Cancer Institute (NCI) . Physical Activity and Cancer. NCI at the National Institutes of Health, Bethesda, MD: (2020). Available at: .
    1. Papadimitriou N, Dimou N, Tsilidis KK, Banbury B, Martin RM, Lewis SJ, et al. . Physical activity and risks of breast and colorectal cancer: a Mendelian randomisation analysis. Nat Commun (2020) 11(1):597. 10.1038/s41467-020-14389-8
    1. Moore SC, Lee IM, Weiderpass E, Campbell PT, Sampson JN, Kitahara CM, et al. . Association of Leisure-Time Physical Activity With Risk of 26 Types of Cancer in 1.44 Million Adults. JAMA Internal Med (2016) 176(6):816–25. 10.1001/jamainternmed.2016.1548
    1. Juiz-Valiña P, Pena-Bello L, Cordido M, Outeiriño-Blanco E, Pértega S, Varela-Rodriguez B, et al. . Altered GH-IGF-1 Axis in Severe Obese Subjects is Reversed after Bariatric Surgery-Induced Weight Loss and Related with Low-Grade Chronic Inflammation. J Clin Med (2020) 9(8):2614. 10.3390/jcm9082614
    1. Fontana L, Weiss EP, Villareal DT, Klein S, Holloszy JO. Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans. Aging Cell (2008) 7(5):681–7. 10.1111/j.1474-9726.2008.00417.x
    1. Kazemi A, Speakman JR, Soltani S, Djafarian K. Effect of calorie restriction or protein intake on circulating levels of insulin like growth factor I in humans: A systematic review and meta-analysis. Clin Nutr (2020) 39(6):1705–16. 10.1016/j.clnu.2019.07.030
    1. Yang HF, Lin XJ, Wang XH. [Effects of aerobic exercise plus diet control on serum levels of total IGF-1 and IGF-1 binding protein-3 in female obese youths and adolescents]. Zhongguo Ying Yong Sheng Li Xue Za Zhi (2018) 34(1):78–82. 10.12047/j.cjap.5571.2018.020
    1. Mason C, Xiao L, Duggan C, Imayama I, Foster-Schubert KE, Kong A, et al. . Effects of dietary weight loss and exercise on insulin-like growth factor-I and insulin-like growth factor-binding protein-3 in postmenopausal women: a randomized controlled trial. Cancer Epidemiol Biomarkers Prev (2013) 22(8):1457–63. 10.1158/1055-9965.EPI-13-0337
    1. Kelly L, Holmberg PM, Schroeder ET, Loza A, Lin X, Moody A, et al. . Effect of home-based strength training program on IGF-I, IGFBP-1 and IGFBP-3 in obese Latino boys participating in a 16-week randomized controlled trial. J Pediatr Endocrinol Metabol: JPEM (2019) 32(10):1121–9. 10.1515/jpem-2019-0073
    1. Al-Regaiey K, Alshubrami S, Al-Beeshi I, Alnasser T, Alwabel A, Al-Beladi H, et al. . Effects of gastric sleeve surgery on the serum levels of GH, IGF-1 and IGF-binding protein 2 in healthy obese patients. BMC Gastroenterol (2020) 20(1):199. 10.1186/s12876-020-01309-9
    1. Bowers LW, Rossi EL, O’Flanagan CH, deGraffenried LA, Hursting SD. The Role of the Insulin/IGF System in Cancer: Lessons Learned from Clinical Trials and the Energy Balance-Cancer Link. Front Endocrinol (Lausanne) (2015) 6:77. 10.3389/fendo.2015.00077
    1. de Groot S, Vreeswijk MP, Welters MJ, Gravesteijn G, Boei JJ, Jochems A, et al. . The effects of short-term fasting on tolerance to (neo) adjuvant chemotherapy in HER2-negative breast cancer patients: a randomized pilot study. BMC Cancer (2015) 15:652. 10.1186/s12885-015-1663-5
    1. Bauersfeld SP, Kessler CS, Wischnewsky M, Jaensch A, Steckhan N, Stange R, et al. . The effects of short-term fasting on quality of life and tolerance to chemotherapy in patients with breast and ovarian cancer: a randomized cross-over pilot study. BMC Cancer (2018) 18(1):476. 10.1186/s12885-018-4353-2
    1. Yamamoto M, Iguchi G, Fukuoka H, Suda K, Bando H, Takahashi M, et al. . SIRT1 regulates adaptive response of the growth hormone–insulin-like growth factor-I axis under fasting conditions in liver. Proc Natl Acad Sci United States America (2013) 110(37):14948–53. 10.1073/pnas.1220606110
    1. Lee C, Safdie FM, Raffaghello L, Wei M, Madia F, Parrella E, et al. . Reduced levels of IGF-I mediate differential protection of normal and cancer cells in response to fasting and improve chemotherapeutic index. Cancer Res (2010) 70(4):1564–72. 10.1158/0008-5472.can-09-3228
    1. Nogueira LM, Dunlap SM, Ford NA, Hursting SD. Calorie restriction and rapamycin inhibit MMTV-Wnt-1 mammary tumor growth in a mouse model of postmenopausal obesity. Endocr Relat Cancer (2012) 19(1):57–68. 10.1530/erc-11-0213
    1. Jin J, Qiu S, Wang P, Liang X, Huang F, Wu H, et al. . Cardamonin inhibits breast cancer growth by repressing HIF-1α-dependent metabolic reprogramming. J Exp Clin Cancer Res: CR (2019) 38(1):377. 10.1186/s13046-019-1351-4
    1. Peng X, Chang H, Gu Y, Chen J, Yi L, Xie Q, et al. . 3,6-Dihydroxyflavone Suppresses Breast Carcinogenesis by Epigenetically Regulating miR-34a and miR-21. Cancer Prev Res (Phila) (2015) 8(6):509–17. 10.1158/1940-6207.Capr-14-0357
    1. Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis (2009) 30(7):1073–81. 10.1093/carcin/bgp127
    1. Del Prete A AP, Santoro G, Fumarulo R, Corsi MM, Mantovani A. Molecular pathways in cancer-related inflammation. Biochem Med (Zagreb) (2011) 21(3):264–75. 10.11613/bm.2011.036
    1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell (2011) 144(5):646–74. 10.1016/j.cell.2011.02.013
    1. Crouch M, Al-Shaer A, Shaikh SR. Hormonal Dysregulation and Unbalanced Specialized Pro-Resolving Mediator Biosynthesis Contribute toward Impaired B Cell Outcomes in Obesity. Mol Nutr Food Res (2021) 65(1):e1900924. 10.1002/mnfr.201900924
    1. Rius J, Guma M, Schachtrup C, Akassoglou K, Zinkernagel AS, Nizet V, et al. . NF-kappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha. Nature (2008) 453(7196):807–11. 10.1038/nature06905
    1. Sica A. Role of tumour-associated macrophages in cancer-related inflammation. Exp Oncol (2010) 32(3):153–8. 10.1007/978-1-4614-0662-4_11
    1. Hagemann T, Lawrence T, McNeish I, Charles KA, Kulbe H, Thompson RG, et al. . “Re-educating” tumor-associated macrophages by targeting NF-kappaB. J Exp Med (2008) 205(6):1261–8. 10.1084/jem.20080108
    1. Stewart DA, Yang Y, Makowski L, Troester MA. Basal-like breast cancer cells induce phenotypic and genomic changes in macrophages. Mol Cancer Res (2012) 10(6):727–38. 10.1158/1541-7786.MCR-11-0604
    1. Hollmen M, Roudnicky F, Karaman S, Detmar M. Characterization of macrophage–cancer cell crosstalk in estrogen receptor positive and triple-negative breast cancer. Sci Rep (2015) 5:9188. 10.1038/srep09188
    1. Dinarello CA. Historical insights into cytokines. Eur J Immunol (2007) 37(Suppl 1):S34–45. 10.1002/eji.200737772
    1. Karin M. Nuclear factor-kappaB in cancer development and progression. Nature (2006) 441(7092):431–6. 10.1038/nature04870
    1. Bukowski RM, Olencki T, McLain D, Finke JH. Pleiotropic effects of cytokines: clinical and preclinical studies. Stem Cells (1994) 12(Suppl 1):129–40. discussion 40-1.
    1. Daghestani HN, Kraus VB. Inflammatory biomarkers in osteoarthritis. Osteoarthr Cartil (2015) 23(11):1890–6. 10.1016/j.joca.2015.02.009
    1. Lappas M. Activation of inflammasomes in adipose tissue of women with gestational diabetes. Mol Cell Endocrinol (2014) 382(1):74–83. 10.1016/j.mce.2013.09.011
    1. Lu H, Ouyang W, Huang C. Inflammation, a key event in cancer development. Mol Cancer Res (2006) 4(4):221–33. 10.1158/1541-7786.MCR-05-0261
    1. Chin AR, Wang SE. Cytokines driving breast cancer stemness. Mol Cell Endocrinol (2014) 382(1):598–602. 10.1016/j.mce.2013.03.024
    1. Ma B, Hottiger MO. Crosstalk between Wnt/beta-Catenin and NF-kappaB Signaling Pathway during Inflammation. Front Immunol (2016) 7:378. 10.3389/fimmu.2016.00378
    1. Jiang X, Shapiro DJ. The immune system and inflammation in breast cancer. Mol Cell Endocrinol (2014) 382(1):673–82. 10.1016/j.mce.2013.06.003
    1. Ono M. Molecular links between tumor angiogenesis and inflammation: inflammatory stimuli of macrophages and cancer cells as targets for therapeutic strategy. Cancer Sci (2008) 99(8):1501–6. 10.1111/j.1349-7006.2008.00853.x
    1. Karki R, Kanneganti TD. Diverging inflammasome signals in tumorigenesis and potential targeting. Nat Rev Cancer (2019) 19(4):197–214. 10.1038/s41568-019-0123-y
    1. Whiteside TL. Regulatory T cell subsets in human cancer: are they regulating for or against tumor progression? Cancer Immunol Immunother (2014) 63(1):67–72. 10.1007/s00262-013-1490-y
    1. Gray MJ, Gong J, Hatch MM, Nguyen V, Hughes CC, Hutchins JT, et al. . Phosphatidylserine-targeting antibodies augment the anti-tumorigenic activity of anti-PD-1 therapy by enhancing immune activation and downregulating pro-oncogenic factors induced by T-cell checkpoint inhibition in murine triple-negative breast cancers. Breast Cancer Res (2016) 18(1):50. 10.1186/s13058-016-0708-2
    1. Chaib M, Chauhan SC, Makowski L. Friend or Foe? Recent Strategies to Target Myeloid Cells in Cancer. Front Cell Dev Biol (2020) 8:3516. 10.3389/fcell.2020.00351
    1. Fleming JM, Miller TC, Kidacki M, Ginsburg E, Stuelten CH, Stewart DA, et al. . Paracrine interactions between primary human macrophages and human fibroblasts enhance murine mammary gland humanization in vivo. Breast Cancer Res (2012) 14(3):R97. 10.1186/bcr3215
    1. Dias JA, Fredrikson GN, Ericson U, Gullberg B, Hedblad B, Engström G, et al. . Low-Grade Inflammation, Oxidative Stress and Risk of Invasive Post-Menopausal Breast Cancer - A Nested Case-Control Study from the Malmö Diet and Cancer Cohort. PloS One (2016) 11(7):e0158959. 10.1371/journal.pone.0158959
    1. Kumar R, Litoff EJ, Boswell WT, Baldwin WS. High fat diet induced obesity is mitigated in Cyp3a-null female mice. Chem Biol Interact (2018) 289:129–40. 10.1016/j.cbi.2018.05.001
    1. Wang K, Chen X, Ward SC, Liu Y, Ouedraogo Y, Xu C, et al. . CYP2A6 is associated with obesity: studies in human samples and a high fat diet mouse model. Int J Obes (Lond) (2019) 43(3):475–86. 10.1038/s41366-018-0037-x
    1. 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. 10.3322/caac.21405
    1. Grimm EA, Sikora AG, Ekmekcioglu S. Molecular pathways: inflammation-associated nitric-oxide production as a cancer-supporting redox mechanism and a potential therapeutic target. Clin Cancer Res (2013) 19(20):5557–63. 10.1158/1078-0432.CCR-12-1554
    1. Levano KS, Jung EH, Kenny PA. Breast cancer subtypes express distinct receptor repertoires for tumor-associated macrophage derived cytokines. Biochem Biophys Res Commun (2011) 411(1):107–10. 10.1016/j.bbrc.2011.06.102
    1. 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. 10.1007/s12609-018-0264-0
    1. Monk JM, Turk HF, Liddle DM, De Boer AA, Power KA, Ma DW, et al. . n-3 polyunsaturated fatty acids and mechanisms to mitigate inflammatory paracrine signaling in obesity-associated breast cancer. Nutrients (2014) 6(11):4760–93. 10.3390/nu6114760
    1. Itoh M, Suganami T, Satoh N, Tanimoto-Koyama K, Yuan X, Tanaka M, et al. . Increased adiponectin secretion by highly purified eicosapentaenoic acid in rodent models of obesity and human obese subjects. Arterioscler Thromb Vasc Biol (2007) 27(9):1918–25. 10.1161/ATVBAHA.106.136853
    1. Rossmeisl M, Jilkova ZM, Kuda O, Jelenik T, Medrikova D, Stankova B, et al. . Metabolic effects of n-3 PUFA as phospholipids are superior to triglycerides in mice fed a high-fat diet: possible role of endocannabinoids. PloS One (2012) 7(6):e38834. 10.1371/journal.pone.0038834
    1. Rossmeisl M, Medrikova D, van Schothorst EM, Pavlisova J, Kuda O, Hensler M, et al. . Omega-3 phospholipids from fish suppress hepatic steatosis by integrated inhibition of biosynthetic pathways in dietary obese mice. Biochim Biophys Acta (2014) 1841(2):267–78. 10.1016/j.bbalip.2013.11.010
    1. MacLennan MB, Clarke SE, Perez K, Wood GA, Muller WJ, Kang JX, et al. . Mammary tumor development is directly inhibited by lifelong n-3 polyunsaturated fatty acids. J Nutr Biochem (2013) 24(1):388–95. 10.1016/j.jnutbio.2012.08.002
    1. Leslie MA, Abdelmagid SA, Perez K, Muller WJ, Ma DW. Mammary tumour development is dose-dependently inhibited by n-3 polyunsaturated fatty acids in the MMTV-neu(ndl)-YD5 transgenic mouse model. Lipids Health Dis (2014) 13:96. 10.1186/1476-511X-13-96
    1. Kanaya N, Adams L, Takasaki A, Chen S. Whole blueberry powder inhibits metastasis of triple negative breast cancer in a xenograft mouse model through modulation of inflammatory cytokines. Nutr Cancer (2014) 66(2):242–8. 10.1080/01635581.2014.863366
    1. Tabung FK, Steck SE, Liese AD, Zhang J, Ma Y, Johnson KC, et al. . Patterns of change over time and history of the inflammatory potential of diet and risk of breast cancer among postmenopausal women. Breast Cancer Res Treat (2016) 159(1):139–49. 10.1007/s10549-016-3925-6
    1. de Almeida-Souza CB, Antunes MM, Godoy G, Schamber CR, Silva M, Bazotte RB. Interleukin-12 as a biomarker of the beneficial effects of food restriction in mice receiving high fat diet or high carbohydrate diet. Braz J Med Biol Res (2018) 51(12):e7900. 10.1590/1414-431X20187900
    1. Lindahl G, Rzepecka A, Dabrosin C. Increased Extracellular Osteopontin Levels in Normal Human Breast Tissue at High Risk of Developing Cancer and Its Association With Inflammatory Biomarkers in situ. Front Oncol (2019) 9:746. 10.3389/fonc.2019.00746
    1. Jaworski DM, Sideleva O, Stradecki HM, Langlois GD, Habibovic A, Satish B, et al. . Sexually dimorphic diet-induced insulin resistance in obese tissue inhibitor of metalloproteinase-2 (TIMP-2)-deficient mice. Endocrinology (2011) 152(4):1300–13. 10.1210/en.2010-1029
    1. Fjaere E, Andersen C, Myrmel LS, Petersen RK, Hansen JB, Tastesen HS, et al. . Tissue Inhibitor Of Matrix Metalloproteinase-1 Is Required for High-Fat Diet-Induced Glucose Intolerance and Hepatic Steatosis in Mice. PloS One (2015) 10(7):e0132910. 10.1371/journal.pone.0132910
    1. Soldati L, Di Renzo L, Jirillo E, Ascierto PA, Marincola FM, De Lorenzo A. The influence of diet on anti-cancer immune responsiveness. J Transl Med (2018) 16(1):75. 10.1186/s12967-018-1448-0
    1. Zeisel SH. Precision (Personalized) Nutrition: Understanding Metabolic Heterogeneity. Annu Rev Food Sci Technol (2020) 11:71–92. 10.1146/annurev-food-032519-051736
    1. Adelman J, Haushofer L. Introduction: Food as Medicine, Medicine as Food. J Hist Med Allied Sci (2018) 73(2):127–34. 10.1093/jhmas/jry010
    1. Witkamp RF, van Norren K. Let thy food be thy medicine….when possible. Eur J Pharmacol (2018) 836:102–14. 10.1016/j.ejphar.2018.06.026
    1. Kim J. Pericytes in Breast Cancer. Adv Exp Med Biol (2019) 1147:93–107. 10.1007/978-3-030-16908-4_3
    1. Guo Y, Zhang S, Yuan H, Song D, Jin S, Guo Z, et al. . A platinum(iv) prodrug to defeat breast cancer through disrupting vasculature and inhibiting metastasis. Dalton Trans (2019) 48(11):3571–5. 10.1039/C9DT00335E
    1. Wagenblast E, Soto M, Gutiérrez-Ángel S, Hartl CA, Gable AL, Maceli AR, et al. . A model of breast cancer heterogeneity reveals vascular mimicry as a driver of metastasis. Nature (2015) 520(7547):358–62. 10.1038/nature14403
    1. Norton K-A, Jin K, Popel AS. Modeling triple-negative breast cancer heterogeneity: Effects of stromal macrophages, fibroblasts and tumor vasculature. J Theor Biol (2018) 452:56–68. 10.1016/j.jtbi.2018.05.003
    1. Yang D, Feng L, Dougherty CA, Luker KE, Chen D, Cauble MA, et al. . In vivo targeting of metastatic breast cancer via tumor vasculature-specific nano-graphene oxide. Biomaterials (2016) 104:361–71. 10.1016/j.biomaterials.2016.07.029
    1. Kozłowski J, Kozłowska A, Kocki J. Breast cancer metastasis - insight into selected molecular mechanisms of the phenomenon. Postepy Hig Med Dosw (2015) 69:447–51. 10.5604/17322693.1148710
    1. Leek RD, Lewis CE, Whitehouse R, Greenall M, Clarke J, Harris AL. Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma. Cancer Res (1996) 56(20):4625–9.
    1. Kolb R, Phan L, Borcherding N, Liu Y, Yuan F, Janowski AM, et al. . Obesity-associated NLRC4 inflammasome activation drives breast cancer progression. Nat Commun (2016) 7:13007. 10.1038/ncomms13007
    1. Kolb R, Kluz P, Tan ZW, Borcherding N, Bormann N, Vishwakarma A, et al. . Obesity-associated inflammation promotes angiogenesis and breast cancer via angiopoietin-like 4. Oncogene (2019) 38(13):2351–63. 10.1038/s41388-018-0592-6
    1. Folkman J. Role of angiogenesis in tumor growth and metastasis. Semin Oncol (2002) 29(6 Suppl 16):15–8. 10.1053/sonc.2002.37263
    1. Esteves M, Monteiro MP, Duarte JA. Role of Regular Physical Exercise in Tumor Vasculature: Favorable Modulator of Tumor Milieu. Int J Sports Med (2020). 10.1055/a-1308-3476
    1. Wen ZH, Su YC, Lai PL, Zhang Y, Xu YF, Zhao A, et al. . Critical role of arachidonic acid-activated mTOR signaling in breast carcinogenesis and angiogenesis. Oncogene (2013) 32(2):160–70. 10.1038/onc.2012.47
    1. Merendino N, Costantini L, Manzi L, Molinari R, D’Eliseo D, Velotti F. Dietary ω -3 polyunsaturated fatty acid DHA: a potential adjuvant in the treatment of cancer. BioMed Res Int (2013) 2013:310186. 10.1155/2013/310186
    1. Darwito D, Dharmana E, Riwanto I, Budijitno S, Suwardjo S, Purnomo J, et al. . Effects of Omega-3 Supplementation on Ki-67 and VEGF Expression Levels and Clinical Outcomes of Locally Advanced Breast Cancer Patients Treated with Neoadjuvant CAF Chemotherapy: A Randomized Controlled Trial Report. Asian Pac J Cancer Prev APJCP (2019) 20(3):911–6. 10.31557/apjcp.2019.20.3.911
    1. Aiyengar TM, Chiranjeevi P, Rani HS. Role of Endothelial Nitric Oxide Synthase in Breast Cancer. In: Saravi SS, editor. Nitric Oxide Synthase - Simple Enzyme-Complex Roles: InTech (2017).
    1. Keshet R, Erez A. Arginine and the metabolic regulation of nitric oxide synthesis in cancer. Dis Models Mech (2018) 11(8):dmm033332. 10.1242/dmm.033332
    1. Kornfeld S, Goupille C, Vibet S, Chevalier S, Pinet A, Lebeau J, et al. . Reducing endothelial NOS activation and interstitial fluid pressure with n –3 PUFA offset tumor chemoresistance. Carcinogenesis (2011) 33(2):260–7. 10.1093/carcin/bgr274
    1. 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):1–14. 10.1186/s13058-019-1153-9
    1. Barone I, Giordano C, Bonofiglio D, Andò S, Catalano S. The weight of obesity in breast cancer progression and metastasis: Clinical and molecular perspectives. Semin Cancer Biol (2020) 60:274–84. 10.1016/j.semcancer.2019.09.001
    1. Haakinson DJ, Leeds SG, Dueck AC, Gray RJ, Wasif N, Stucky C-CH, et al. . The Impact of Obesity on Breast Cancer: A Retrospective Review. Breast Oncol (2012) 19: (9):3012–8. 10.1245/s10434-012-2320-8
    1. Osman MA, Hennessy BT. Obesity Correlation with Metastases Development and Response to First-Line Metastatic Chemotherapy in Breast Cancer. Clin Med Insights: Oncol (2015) 9:CMO.S32812. 10.4137/cmo.s32812
    1. Bousquenaud M, Fico F, Solinas G, Rüegg C, Santamaria-Martínez A. Obesity promotes the expansion of metastasis-initiating cells in breast cancer. Breast Cancer Res (2018) 20(104). 10.1186/s13058-018-1029-4
    1. Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, et al. . Human Adipose Tissue Is a Source of Multipotent Stem Cells. Mol Biol Cell (2002) 13(12):4279–95. 10.1091/mbc.e02-02-0105
    1. Janssen LME, Ramsay EE, Logsdon CD, Overwijk WW. The immune system in cancer metastasis: friend or foe? J ImmunoTher Cancer (2017) 5(1):1–14. 10.1186/s40425-017-0283-9
    1. Coffelt SB, Wellenstein MD, De Visser KE. Neutrophils in cancer: neutral no more. Nat Rev Cancer (2016) 16(7):431–46. 10.1038/nrc.2016.52
    1. Quail DF, Olson OC, Bhardwaj P, Walsh LA, Akkari L, Quick ML, et al. . Obesity alters the lung myeloid cell landscape to enhance breast cancer metastasis through IL5 and GM-CSF. Nat Cell Biol (2017) 19(8):974–87. 10.1038/ncb3578
    1. Cozzo AJ, Fuller, Ashley M, Makowski L. Contribution of Adipose Tissue to Development of Cancer. Compr Physiol (2018) 8(1):237–82. 10.1002/cphy.c170008
    1. Donohoe CL, Lysaght J, O’Sullivan J, Reynolds JV. Emerging Concepts Linking Obesity with the Hallmarks of Cancer. Trends Endocrinol Metabol (2016) 28(1):46–62. 10.1016/j.tem.2016.08.004
    1. Joint WHOFAOUNUEC . Protein and amino acid requirements in human nutrition. World Health Organ Tech Rep Ser (2007) (935):1–265.
    1. Rand WM, Pellett PL, Young VR. Meta-analysis of nitrogen balance studies for estimating protein requirements in healthy adults. Am J Clin Nutr (2003) 77(1):109–27. 10.1093/ajcn/77.1.109
    1. Medicine. Io . Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. Washington, DC: The National Academies Press; (2006).
    1. Medicine. Io . Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. The National Academies Collection: Reports funded by National Institutes of Health. Washington (DC: The National Academies Press; (1997) p. 1–449.
    1. Medicine. Io . Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington (DC: The National Academies Press; (2000) p. 1–530.
    1. Medicine. Io . Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press; (2005).
    1. Medicine. Io . Dietary Reference Intakes Research Synthesis: Workshop Summary. Washington, DC: The National Academies Press; (2006).
    1. National Academies of Sciences E, and Medicine . Dietary Reference Intakes for Sodium and Potassium. In: Oria M, Harrison M, Stallings VA, editors. Dietary Reference Intakes for Sodium and Potassium. The National Academies Collection: Reports funded by National Institutes of Health. Washington (DC: The National Academies Press; (2019). p. 1–595.
    1. National Academies of Sciences E . Medicine. Guiding Principles for Developing Dietary Reference Intakes Based on Chronic Disease. Kumanyika S, Oria MP, editors. Washington, DC: The National Academies Press; (2017). p. 334.
    1. U.S. Department of Health and Human Services and U.S. Department of Agriculture . 2015–2020 Dietary Guidelines for Americans. 8th Edition. Washington, D. C. (2015) p. 1–144.
    1. National Academies of Sciences E, and Medicine . A Health Equity Approach to Obesity Efforts: Proceedings of a Workshop. In: Callahan EA, editor. A Health Equity Approach to Obesity Efforts: Proceedings of a Workshop. Washington (DC: The National Academies Press; (2019). p. 1–123.
    1. Speakman JR. Use of high-fat diets to study rodent obesity as a model of human obesity. Int J Obes (Lond) (2019) 43(8):1491–2. 10.1038/s41366-019-0363-7
    1. Hu S, Wang L, Yang D, Li L, Togo J, Wu Y, et al. . Dietary Fat, but Not Protein or Carbohydrate, Regulates Energy Intake and Causes Adiposity in Mice. Cell Metab (2018) 28(3):415–31 e4. 10.1016/j.cmet.2018.06.010
    1. Ning M, Jeong H. High-Fat Diet Feeding Alters Expression of Hepatic Drug-Metabolizing Enzymes in Mice. Drug Metab Dispos (2017) 45(7):707–11. 10.1124/dmd.117.075655
    1. Núñez NP CC, Perkins SN, Berrigan D, Jaque SV, Ingles SA, Bernstein L, et al. . Extreme obesity reduces bone mineral density: complementary evidence from mice and women. Obes (Silver Spring) (2007) 15(8):1980–7. 10.1038/oby.2007.236
    1. Sadler NC, Webb-Robertson BM, Clauss TR, Pounds JG, Corley R, Wright AT. High-Fat Diets Alter the Modulatory Effects of Xenobiotics on Cytochrome P450 Activities. Chem Res Toxicol (2018) 31(5):308–18. 10.1021/acs.chemrestox.8b00008
    1. Clemmensen C, Smajilovic S, Madsen AN, Klein AB, Holst B, Brauner-Osborne H. Increased susceptibility to diet-induced obesity in GPRC6A receptor knockout mice. J Endocrinol (2013) 217(2):151–60. 10.1530/JOE-12-0550
    1. De Angel RE, Blando JM, Hogan MG, Sandoval MA, Lansakara PD, Dunlap SM, et al. . Stearoyl gemcitabine nanoparticles overcome obesity-induced cancer cell resistance to gemcitabine in a mouse postmenopausal breast cancer model. Cancer Biol Ther (2013) 14(4):357–64. 10.4161/cbt.23623
    1. Ford NA, Rossi EL, Barnett K, Yang P, Bowers LW, Hidaka BH, et al. . Omega-3-Acid Ethyl Esters Block the Protumorigenic Effects of Obesity in Mouse Models of Postmenopausal Basal-like and Claudin-Low Breast Cancer. Cancer Prev Res (Phila) (2015) 8(9):796–806. 10.1158/1940-6207.CAPR-15-0018
    1. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med (2003) 348(17):1625–38. 10.1056/NEJMoa021423
    1. Chen S, Chen CM, Zhou Y, Zhou RJ, Yu KD, Shao ZM. Obesity or overweight is associated with worse pathological response to neoadjuvant chemotherapy among Chinese women with breast cancer. PloS One (2012) 7(7):e41380. 10.1371/journal.pone.0041380
    1. Shi Z, Rundle A, Genkinger JM, Cheung YK, Ergas IJ, Roh JM, et al. . Distinct trajectories of fruits and vegetables, dietary fat, and alcohol intake following a breast cancer diagnosis: the Pathways Study. Breast Cancer Res Treat (2020) 179(1):229–40. 10.1007/s10549-019-05457-9
    1. 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. 10.1016/j.clbc.2012.07.013
    1. Dydjow-Bendek D, Zagozdzon P. Total Dietary Fats, Fatty Acids, and Omega-3/Omega-6 Ratio as Risk Factors of Breast Cancer in the Polish Population - a Case-Control Study. In Vivo (2020) 34(1):423–31. 10.21873/invivo.11791
    1. Go Y, Chung M, Park Y. Dietary Patterns for Women With Triple-negative Breast Cancer and Dense Breasts. Nutr Cancer (2016) 68(8):1281–8. 10.1080/01635581.2016.1225102
    1. Prieto-Hontoria PL, Perez-Matute P, Fernandez-Galilea M, Bustos M, Martinez JA, Moreno-Aliaga MJ. Role of obesity-associated dysfunctional adipose tissue in cancer: a molecular nutrition approach. Biochim Biophys Acta (2011) 1807(6):664–78. 10.1016/j.bbabio.2010.11.004
    1. Christ A, Lauterbach M, Latz E. Western Diet and the Immune System: An Inflammatory Connection. Immunity (2019) 51(5):794–811. 10.1016/j.immuni.2019.09.020
    1. Hariharan D, Vellanki K, Kramer H. The Western Diet and Chronic Kidney Disease. Curr Hypertens Rep (2015) 17(3):16. 10.1007/s11906-014-0529-6
    1. Hintze KJ, Benninghoff AD, Cho CE, Ward RE. Modeling the Western Diet for Preclinical Investigations. Adv Nutr (Bethesda Md) (2018) 9(3):263–71. 10.1093/advances/nmy002
    1. Shively CA, Register TC, Appt SE, Clarkson TB, Uberseder B, Clear KYJ, et al. . Consumption of Mediterranean versus Western Diet Leads to Distinct Mammary Gland Microbiome Populations. Cell Rep (2018) 25(1):47–56.e3. 10.1016/j.celrep.2018.08.078
    1. Varlamov O. Western-style diet, sex steroids and metabolism. Biochim Biophys Acta Mol Basis Dis (2017) 1863(5):1147–55. 10.1016/j.bbadis.2016.05.025
    1. Zinöcker MK, Lindseth IA. The Western Diet-Microbiome-Host Interaction and Its Role in Metabolic Disease. Nutrients (2018) 10(3). 10.3390/nu10030365
    1. Ho VW, Leung K, Hsu A, Luk B, Lai J, Shen SY, et al. . A low carbohydrate, high protein diet slows tumor growth and prevents cancer initiation. Cancer Res (2011) 71(13):4484–93. 10.1158/0008-5472.CAN-10-3973
    1. Kiilerich P, Myrmel LS, Fjaere E, Hao Q, Hugenholtz F, Sonne SB, et al. . Effect of a long-term high-protein diet on survival, obesity development, and gut microbiota in mice. Am J Physiol Endocrinol Metab (2016) 310(11):E886–99. 10.1152/ajpendo.00363.2015
    1. Moulton CJVR, Layman DK, Devkota S, Singletary KW, Wallig MA, Donovan SM. A high protein moderate carbohydrate diet fed at discrete meals reduces early progression of N-methyl-N-nitrosourea-induced breast tumorigenesis in rats. Nutr Metab (Lond) (2010) 7(1):1–7. 10.1186/1743-7075-7-1
    1. Park YM, Steck SE, Fung TT, Merchant AT, Elizabeth Hodgson M, Keller JA, et al. . Higher diet-dependent acid load is associated with risk of breast cancer: Findings from the sister study. Int J Cancer (2019) 144(8):1834–43. 10.1002/ijc.31889
    1. Levine ME, Suarez JA, Brandhorst S, Balasubramanian P, Cheng CW, Madia F, et al. . Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population. Cell Metab (2014) 19(3):407–17. 10.1016/j.cmet.2014.02.006
    1. Mittendorfer B, Klein S, Fontana L. A word of caution against excessive protein intake. Nat Rev Endocrinol (2020) 16(1):59–66. 10.1038/s41574-019-0274-7
    1. Castelló A, Pollán M, Buijsse B, Ruiz A, Casas AM, Baena-Cañada JM, et al. . Spanish Mediterranean diet and other dietary patterns and breast cancer risk: case–control EpiGEICAM study. Br J Cancer (2014) 111(7):1454–62. 10.1038/bjc.2014.434
    1. Limon-Miro AT, Lopez-Teros V, Astiazaran-Garcia H. Dietary Guidelines for Breast Cancer Patients: A Critical Review. Adv Nutr (Bethesda Md) (2017) 8(4):613–23. 10.3945/an.116.014423
    1. De Cicco P, Catani MV, Gasperi V, Sibilano M, Quaglietta M, Savini I. Nutrition and Breast Cancer: A Literature Review on Prevention, Treatment and Recurrence. Nutrients (2019) 11(7):1–28. 10.3390/nu11071514
    1. Naghshi S, Sadeghi O, Willett WC, Esmaillzadeh A. Dietary intake of total, animal, and plant proteins and risk of all cause, cardiovascular, and cancer mortality: systematic review and dose-response meta-analysis of prospective cohort studies. BMJ (2020) 370(m2412):1–17. 10.1136/bmj.m2412

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa