Reactive oxygen species (ROS): Critical roles in breast tumor microenvironment

ROS in breast carcinogenesis and TME reprogramming. ROS promotes carcinogenesis by damaging proteins, membrane lipids, and nucleic acids. They also promote reprogramming of cancer, stromal and immune cells by various mechanisms. Therapeutic strategies based on ROS modulation such as phytochemicals, chemotherapeutics, gene therapy, nanotherapy, and immune therapy can target the TME and reduces breast cancer metastasis. [Display omitted] •ROS promote the reprogramming of breast TME cells by various mechanisms.•They promote genetic and epigenetic changes, metastasis, and drug resistance.•ROS mediate TME regulation by microRNA, exosomes, and autophagy.•Phytochemical responsive ROS target TME signaling pathways.•Chemotherapeutic responsive ROS enhance antitumor immunity. Increases in Reactive oxygen species (ROS) have been reported in breast tumors and their surrounding tumor microenvironment (TME) cells. ROS are critical factors in breast TME as they ensure bidirectional communication among various components and mediate multi-faceted roles in tumor progression and metastasis. This paper presents a detailed and comprehensive review of the studies exploring ROS and various forms of oxidative stress in cancer progression, specifically breast cancer (BC), its microenvironment and associated cell types. The paper focuses on several diverse aspects of cellular and molecular biology of cancer, with pharmacological implications of phytochemicals in BC. We also describe the role of ROS in the genetic and epigenetic reprogramming of the TME, metastasis, and drug resistance as well as regulators of BC TME. Additionally, we discuss ROS-mediated TME therapy and the therapeutic conundrum of breast TME. These contributions could prompt the development of personalized anti-cancer drugs for the treatment of highly complex and aggressive BCs.