The Impact of Estrogen Levels on the Development of Breast Cancer in Postmenopausal Women with Diagnosed Obesity or Overweight
DOI:
https://doi.org/10.12775/QS.2026.49.67137Keywords
breast cancer, estrogens, estrogen receptors, postmenopausal, hormone therapy, aromatase inhibitors, oncogenesis, tumor cell proliferation, estrogen receptor modulators, therapeutic strategies, obesityAbstract
Breast cancer is one of the most commonly diagnosed malignancies in women. Its development is largely influenced by hormonal factors. Estrogens, as key female sex hormones, play a crucial role in the proliferation of mammary gland cells, which may contribute to the initiation and progression of tumorigenesis. In postmenopausal women, estrogens are primarily derived from the conversion of androgens in adipose tissue, leading to hormonal changes that impact breast cancer risk.
This study aims to examine the influence of estrogen levels on breast cancer development in postmenopausal women with overweight and obesity, as well as to elucidate the underlying biological mechanisms of this association. The molecular actions of estrogens and their effects on estrogen receptor (ER) expression in the context of breast cancer will be discussed. Additionally, the role of obesity as a risk factor for breast cancer in postmenopausal women will be presented.
This article seeks to enhance the understanding of the role of obesity in oncogenesis among women whose physiological estrogen levels should correspond to their age-appropriate hormonal balance.
References
[1] Barzaman K, Karami J, Zarei Z, Hosseinzadeh A, Kazemi MH, Moradi-Kalbolandi S, Safari E, Farahmand L. Breast cancer: Biology, biomarkers, and treatments. Int Immunopharmacol. 2020 Jul;84:106535. doi: 10.1016/j.intimp.2020.106535. Epub 2020 Apr 29. PMID: 32361569.
[2] Nagarajan, D.; McArdle, S.E.B. Immune Landscape of Breast Cancers. Biomedicines 2018, 6, 20. https://doi.org/10.3390/biomedicines6010020
[3] Linda Björnström, Maria Sjöberg, Mechanisms of Estrogen Receptor Signaling: Convergence of Genomic and Nongenomic Actions on Target Genes, Molecular Endocrinology, Volume 19, Issue 4, 1 April 2005, Pages 833–842, https://doi.org/10.1210/me.2004-0486
[4] Burns, K.A., Korach, K.S. Estrogen receptors and human disease: an update. Arch Toxicol 86, 1491–1504 (2012). https://doi.org/10.1007/s00204-012-0868-5
[5] Williams Cecilia, Lin Chin-Yo (2013) Oestrogen receptors in breast cancer: basic mechanisms and clinical implications ecancer 7 370
[6] Prall OW, Rogan EM, Musgrove EA, Watts CK, Sutherland RL. c-Myc or cyclin D1 mimics estrogen effects on cyclin E-Cdk2 activation and cell cycle reentry. Mol Cell Biol. 1998 Aug;18(8):4499-508. doi: 10.1128/MCB.18.8.4499. PMID: 9671459; PMCID: PMC109035.
[7] Zhu J, Blenis J, Yuan J. Activation of PI3K/Akt and MAPK pathways regulates Myc-mediated transcription by phosphorylating and promoting the degradation of Mad1. Proc Natl Acad Sci U S A. 2008 May 6;105(18):6584-9. doi: 10.1073/pnas.0802785105. Epub 2008 May 1. PMID: 18451027; PMCID: PMC2373325.
[8] Finn, R.S., Aleshin, A. & Slamon, D.J. Targeting the cyclin-dependent kinases (CDK) 4/6 in estrogen receptor-positive breast cancers. Breast Cancer Res 18, 17 (2016). https://doi.org/10.1186/s13058-015-0661-5
[9] Cariou S, Donovan JC, Flanagan WM, Milic A, Bhattacharya N, Slingerland JM. Down-regulation of p21WAF1/CIP1 or p27Kip1 abrogates antiestrogen-mediated cell cycle arrest in human breast cancer cells. Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):9042-6. doi: 10.1073/pnas.160016897. PMID: 10908655; PMCID: PMC16818.
[10] Sasanuma H, Tsuda M, Morimoto S, Saha LK, Rahman MM, Kiyooka Y, Fujiike H, Cherniack AD, Itou J, Callen Moreu E, Toi M, Nakada S, Tanaka H, Tsutsui K, Yamada S, Nussenzweig A, Takeda S. BRCA1 ensures genome integrity by eliminating estrogen-induced pathological topoisomerase II-DNA complexes. Proc Natl Acad Sci U S A. 2018 Nov 6;115(45):E10642-E10651. doi: 10.1073/pnas.1803177115. Epub 2018 Oct 23. PMID: 30352856; PMCID: PMC6233096.
[11] Richard J. Santen, Wei Yue, Ji-Ping Wang, Estrogen metabolites and breast cancer, Steroids,
Volume 99, Part A, 2015, Pages 61-66, ISSN 0039-128X, https://doi.org/10.1016/j.steroids.2014.08.003.
[12] Periyasamy, L. et al. (2022). Reactive Oxygen Species: Induced Epigenetic Modification in the Expression Pattern of Oncogenic Proteins. In: Chakraborti, S. (eds) Handbook of Oxidative Stress in Cancer: Therapeutic Aspects. Springer, Singapore. https://doi.org/10.1007/978-981-16-1247-3_68-1
[13] Molinelli C, Jacobs F, Agostinetto E, Nader-Marta G, Ceppi M, Bruzzone M, Blondeaux E, Schettini F, Prat A, Viale G, Del Mastro L, Lambertini M, de Azambuja E. Prognostic value of HER2-low status in breast cancer: a systematic review and meta-analysis. ESMO Open. 2023 Aug;8(4):101592. doi: 10.1016/j.esmoop.2023.101592. Epub 2023 Jul 4. PMID: 37413762; PMCID: PMC10485402.
[14] Biuletyn Polskiego Towarzystwa Onkologicznego, NOWOTWORY 2017, tom 2, nr 6, 448–458 © Polskie Towarzystwo Onkologiczne, ISSN 2543–5248.
[15] 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 May 5;466:15-30. doi: 10.1016/j.mce.2017.09.014. Epub 2017 Sep 15. PMID: 28919302.
[16] Bulun SE, Chen D, Moy I, Brooks DC, Zhao H. Aromatase, breast cancer and obesity: a complex interaction. Trends Endocrinol Metab. 2012 Feb;23(2):83-9. doi: 10.1016/j.tem.2011.10.003. Epub 2011 Dec 12. PMID: 22169755; PMCID: PMC3428377.
[17] Enriori CL, Reforzo-Membrives J. Peripheral aromatization as a risk factor for breast and endometrial cancer in postmenopausal women: a review. Gynecol Oncol. 1984 Jan;17(1):1-21. doi: 10.1016/0090-8258(84)90055-6. PMID: 6319245.
[18] Khan S, Shukla S, Sinha S, Meeran SM. Role of adipokines and cytokines in obesity-associated breast cancer: therapeutic targets. Cytokine Growth Factor Rev. 2013 Dec;24(6):503-13. doi: 10.1016/j.cytogfr.2013.10.001. Epub 2013 Oct 21. PMID: 24210902.
[19] Szablewski L. Insulin Resistance: The Increased Risk of Cancers. Curr Oncol. 2024 Feb 13;31(2):998-1027. doi: 10.3390/curroncol31020075. PMID: 38392069; PMCID: PMC10888119.
[20] Tsugane S, Inoue M. Insulin resistance and cancer: epidemiological evidence. Cancer Sci. 2010 May;101(5):1073-9. doi: 10.1111/j.1349-7006.2010.01521.x. Epub 2010 Feb 3. PMID: 20345478; PMCID: PMC11159937.
[21] Arcidiacono B, Iiritano S, Nocera A, Possidente K, Nevolo MT, Ventura V, Foti D, Chiefari E, Brunetti A. Insulin resistance and cancer risk: an overview of the pathogenetic mechanisms. Exp Diabetes Res. 2012;2012:789174. doi: 10.1155/2012/789174. Epub 2012 Jun 4. PMID: 22701472; PMCID: PMC3372318.
[22] Iyengar, N.M., Morris, P.G., Hudis, C.A., Dannenberg, A.J. (2013). Obesity, Inflammation, and Breast Cancer. In: Dannenberg, A., Berger, N. (eds) Obesity, Inflammation and Cancer. Energy Balance and Cancer, vol 7. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6819-6_8
[23] Artac, M., Altundag, K. Leptin and breast cancer: an overview. Med Oncol 29, 1510–1514 (2012). https://doi.org/10.1007/s12032-011-0056-0
[24] Kelesidis I, Kelesidis T, Mantzoros CS. Adiponectin and cancer: a systematic review. Br J Cancer. 2006 May 8;94(9):1221-5. doi: 10.1038/sj.bjc.6603051. PMID: 16570048; PMCID: PMC2361397.
[25] Kubiak, Tomasz. "Correlation between iron metabolism and development of breast cancer
in pre- and postmenopausal women." Menopause Review/Przegląd Menopauzalny, vol. 12, no. 4, 2013, pp. 339-342. doi:10.5114/pm.2013.37852.
[26] Włodarczyk, M.; Nowicka, G. Obesity, DNA Damage, and Development of Obesity-Related Diseases. Int. J. Mol. Sci. 2019, 20, 1146. https://doi.org/10.3390/ijms20051146
[27] Dietze EC, Chavez TA, Seewaldt VL. Obesity and Triple-Negative Breast Cancer: Disparities, Controversies, and Biology. Am J Pathol. 2018 Feb;188(2):280-290. doi: 10.1016/j.ajpath.2017.09.018. Epub 2017 Nov 9. PMID: 29128565; PMCID: PMC5785535.
[28] Simpson, E. R., & Brown, K. A. (2013). Obesity and breast cancer: role of inflammation and aromatase. Journal of Molecular Endocrinology, 51(3), T51-T59. Retrieved Mar 2, 2025, from https://doi.org/10.1530/JME-13-0217
[29] Ioannides SJ, Barlow PL, Elwood JM, Porter D. Effect of obesity on aromatase inhibitor efficacy in postmenopausal, hormone receptor-positive breast cancer: a systematic review. Breast Cancer Res Treat. 2014 Sep;147(2):237-48. doi: 10.1007/s10549-014-3091-7. Epub 2014 Aug 14. PMID: 25119728.
[30] Slawinski CGV, Barriuso J, Guo H, Renehan AG. Obesity and Cancer Treatment Outcomes: Interpreting the Complex Evidence. Clin Oncol (R Coll Radiol). 2020 Sep;32(9):591-608. doi: 10.1016/j.clon.2020.05.004. Epub 2020 Jun 25. PMID: 32595101.
[31] Vucenik I, Stains JP. Obesity and cancer risk: evidence, mechanisms, and recommendations. Ann N Y Acad Sci. 2012 Oct;1271(1):37-43. doi: 10.1111/j.1749-6632.2012.06750.x. PMID: 23050962; PMCID: PMC3476838.
[32] Jiralerspong S, Goodwin PJ. Obesity and Breast Cancer Prognosis: Evidence, Challenges, and Opportunities. J Clin Oncol. 2016 Dec 10;34(35):4203-4216. doi: 10.1200/JCO.2016.68.4480. Epub 2016 Nov 7. PMID: 27903149.
[33] Harborg. Obesity and Risk of Recurrence in Patients With Breast Cancer Treated With
Aromatase Inhibitors. JAMA Netw Open. Published October 13, 2023.
doi:10.1001/jamanetworkopen.2023.37780
[34] Harborg, Sixten & Zachariae, Robert & Olsen, Julia & Johannsen, Maja & Cronin-Fenton, Deirdre & Bøggild, Henrik & Borgquist, Signe. (2021). Overweight and prognosis in triple-negative breast cancer patients: a systematic review and meta-analysis. npj Breast Cancer. 7. 119. 10.1038/s41523-021-00325-6.
[35] Holly R. Harris, Walter C. Willett, Kathryn L. Terry, Karin B. Michels, Body Fat Distribution and Risk of Premenopausal Breast Cancer in the Nurses’ Health Study II, JNCI: Journal of the National Cancer Institute, Volume 103, Issue 3, 2 February 2011, Pages 273–278, https://doi.org/10.1093/jnci/djq500
[36] Pan K, Nelson RA, Wactawski-Wende J, Lee DJ, Manson JE, Aragaki AK, Mortimer JE, Phillips LS, Rohan T, Ho GYF, Saquib N, Shadyab AH, Nassir R, Rhee JJ, Hurria A, Chlebowski RT. Insulin Resistance and Cancer-Specific and All-Cause Mortality in Postmenopausal Women: The Women's Health Initiative. J Natl Cancer Inst. 2020 Feb 1;112(2):170-178. doi: 10.1093/jnci/djz069. PMID: 31184362; PMCID: PMC7019097.
[37] Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data on 53 297 women with breast cancer and 100 239 women without breast cancer from 54 epidemiological studies. Lancet. 1996 Jun 22;347(9017):1713-27. doi: 10.1016/s0140-6736(96)90806-5. PMID: 8656904.
[38] Freeman EW, Sammel MD, Lin H, Gracia CR. Obesity and reproductive hormone levels in the transition to menopause. Menopause. 2010 Jul;17(4):718-26. doi: 10.1097/gme.0b013e3181cec85d. PMID: 20216473; PMCID: PMC2888623.
[39] Siregar MF, Terauchi M, Sari RA, Adella CA, Prabudi MO, Barus MN, Rivany R, Tobing ID, Azmeila S. Comparison of leptin and estrone levels between normal body mass index and obese menopausal women. Narra J. 2024 Aug;4(2):e745. doi: 10.52225/narra.v4i2.745. Epub 2024 May 27. PMID: 39280324; PMCID: PMC11391983.
[40] Mahabir S, Baer DJ, Johnson LL, Hartman TJ, Dorgan JF, Campbell WS, Clevidence BA, Taylor PR. Usefulness of body mass index as a sufficient adiposity measurement for sex hormone concentration associations in postmenopausal women. Cancer Epidemiol Biomarkers Prev. 2006 Dec;15(12):2502-7. doi: 10.1158/1055-9965.EPI-06-0499. PMID: 17164376.
[41] Karim R, Mack WJ, Hodis HN, Roy S, Stanczyk FZ. Influence of age and obesity on serum estradiol, estrone, and sex hormone binding globulin concentrations following oral estrogen administration in postmenopausal women. J Clin Endocrinol Metab. 2009 Nov;94(11):4136-43. doi: 10.1210/jc.2009-0643. Epub 2009 Oct 6. PMID: 19808850; PMCID: PMC2775642.
[42] Cyganek, K., Katra, B., & Sieradzki, J. (2005). Porównanie pomiaru tkanki tłuszczowej u otyłych chorych metodą impedancji i densytometryczną. XVIII Zjazd Polskiego Towarzystwa Endokrynologicznego, Kraków, 22-25.09.2005. Katedra i Klinika Chorób Metabolicznych, Collegium Medicum, Uniwersytet Jagielloński.
[43] American Diabetes Association. (2023). Standards of medical care in diabetes—2023. Diabetes Care, 46(Suppl. 1), S1–S291. https://doi.org/10.2337/dc23-Srev
[44] Campos, A. M. R., Andrade, C. R., & Ferreira, S. R. G. (2024). Reference values for insulin and HOMA-IR in Brazilian adults without obesity and metabolic disorders: Results from the ELSA-Brasil study. Archives of Endocrinology and Metabolism, ahead of print. https://pubmed.ncbi.nlm.nih.gov/39529982
[45] Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. (2002). 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) final report. Circulation, 106(25), 3143–3421. https://doi.org/10.1161/circ.106.25.3143
[46] Engin, A. (2017). Obesity-associated Breast Cancer: Analysis of risk factors. Advances in Experimental Medicine and Biology, 571–606. doi:10.1007/978-3-319-48382-5_25
[47] Ding S, Madu CO, Lu Y. The Impact of Hormonal Imbalances Associated with Obesity on the Incidence of Endometrial Cancer in Postmenopausal Women. J Cancer 2020; 11(18):5456-5465. doi:10.7150/jca.47580. https://www.jcancer.org/v11p5456.htm
[48] Soni AC, Conroy MB, Mackey RH, Kuller LH. Ghrelin, leptin, adiponectin, and insulin levels and concurrent and future weight change in overweight, postmenopausal women. Menopause. 2011 Mar;18(3):296-301. doi: 10.1097/gme.0b013e3181f2e611. PMID: 21449093; PMCID: PMC3069721.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Jakub Pochopień, Mikołaj Pograniczny, Adrianna Mielżyńska, Adrianna Pacołta, Marcelina Nalepka
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Stats
Number of views and downloads: 13
Number of citations: 0
