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The review links hyperglycemia to mTOR activation, emphasizes estrogen’s centrality in estrogen-receptor-positive breast cancer, and highlights the need to further investigate ROS in both pathogenesis and therapy. 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The Role of Obesity in Breast Cancer Pathogenesis. Cells 2023, 12, 2061 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)cells12162061  \nAcademic Editors: Robert Clarke and Abhishek Tyagi  \nReceived: 22 May 2023  \nRevised: 3 August 2023  \nAccepted: 11 August 2023  \nPublished: 14 August 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA; [nghia.le@westernu.edu](nghia.le@westernu.edu) (N.L.); [aamna.asif@westernu.edu](aamna.asif@westernu.edu) (A.A.); [cheldonann.alcantara@westernu.edu](cheldonann.alcantara@westernu.edu) (C.A.A.); [mercedeh.mirhosseini@westernu.edu](mercedeh.mirhosseini@westernu.edu) (M.M.)  \n2 Corona Regional Medical Center, Department of Emergency Medicine, Corona, CA 92882, USA  \n* [Correspondence: vvenketaraman@westernu.edu](Correspondence: vvenketaraman@westernu.edu)  \nAbstract: Research has shown that obesity increases the risk for type 2 diabetes mellitus (Type 2 DM) by promoting insulin resistance, increases serum estrogen levels by the upregulation of aromatase, and promotes the release of reactive oxygen species (ROS) by macrophages. Increased circulating glucose has been shown to activate mammalian target of rapamycin (mTOR), a significant signaling pathway in breast cancer pathogenesis. Estrogen plays an instrumental role in estrogenreceptor-positive breast cancers. The role of ROS in breast cancer warrants continued investigation, in relation to both pathogenesis and treatment of breast cancer. We aim to review the role of obesity in breast cancer pathogenesis and novel therapies mediating obesity-associated breast cancer development. We explore the association between body mass index (BMI) and breast cancer incidence and the mechanisms by which oxidative stress modulates breast cancer pathogenesis. We discuss the role of glutathione, a ubiquitous antioxidant, in breast cancer therapy. Lastly, we review breast cancer therapies targeting mTOR signaling, leptin signaling, blood sugar reduction, and novel immunotherapy targets.  \nKeywords: obesity; diabetes mellitus; breast cancer; glutathione; mTOR; leptin; BMI  \n1. Introduction  \nAccording to the American Cancer Society (ACS), an estimated 300,590 new cases and 43,700 deaths due to breast cancer are expected in the US in 2023 [1] . Breast cancer is the most common malignancy diagnosed in women worldwide; it is estimated that the risk of a woman developing breast cancer in her lifetime is 12.9%[1] . Concurrently, the CDC reports that the US is experiencing unprecedented increases in obesity, with obesity prevalence increasing from 30.5% in 2017 to 41.9% in March 2020, and during this period, the prevalence of severe obesity increased from 4.7% to 9.2% .  \nThe growing obesity epidemic has nearly tripled since 1975 . Obesity is a complex and multifactorial disease which leads to an increased risk of morbidity and mortality [2] . Obesity can be affected by genetic, behavioral, socioeconomic, and environmental factors. While these factors play an important role, changes in diet and lifestyle have had the biggest impact on the rise in obesity. Globally, there has been an amplified intake of energydense foods ","cbCaibhT7HzLckWu","https://ap.wps.com/l/cbCaibhT7HzLckWu","pdf",1254042,24,"English","# Introduction\n## Obesity as a multifactorial disease and its health impact\n## Diabetes, insulin resistance, and pancreatic beta-cell dysfunction\n## Links between obesity, metabolic syndrome, and breast cancer risk","[{\"question\":\"Which therapeutic targets related to obesity are discussed?\",\"answer\":\"The review addresses therapies targeting mTOR signaling and leptin signaling, approaches aimed at blood-sugar reduction, and novel immunotherapy targets. It also discusses the role of glutathione as an antioxidant in breast cancer therapy.\"}]","The Role of Obesity in Breast Cancer Pathogenesis | PDF",1790239769]