Introduction: Reactive oxygen and nitrogen species (RONS) are produced by several endogenous and exogenous processes, and their negative effects are neutralized by antioxidant defenses. Oxidative stress (OS) occurs from the imbalance between RONS production and these antioxidant defenses. Previous studies indicate the important roles of oxidative stress in different tumour pathogenesis including colorectal, bladder, endometrial carcinoma and breast cancer. Breast carcinoma is one of the most common neoplasms in women and is a leading cause of cancer-related deaths worldwide. We conducted this review to summarize the most recent published literature on oxidative stress biomarkers and breast cancer.
Methods: A review literature search of eligible studies was conducted in PubMed database from 2010 to 2021 for studies evaluating the association between oxidative stress and breast cancer using the following search strategy: ("oxidative stress" OR "RONS") AND ("breast carcinoma" or "breast cancer") as keywords. Studies (systematic review and metanalysis) were included in this review.
Results: Studies suggest that in this disease oxidative stress is increased. Many mechanisms are effective in enhancing oxidative stress, including genetic variations in antioxidant enzymes, estrogen therapy, and excess reactive oxygen species. It has been shown that breast carcinoma DNA contains high concentrations of base modifications. An increased level of 8-hydroxy-2′-deoxyguanosine (8-OHdG) was observed in estrogen receptor (ER) positive malignant tissues which suggests that ROS may play an important role in the early phases of carcinogenesis. Moreover, increased ROS has been found in the tumor environment that plays an important role in cancer progression by altering the expression of suppressor genes involved in apoptosis, increasing the expression of cytokines involved in angiogenesis, creates changes in the connections between cells and their effects on the metalloproteinase activity of proteinase involved in metastasis.
Conclusion: Destruction caused by oxidative stress has an impressive role in the occurrence and progression of breast cancer. In other words, an increase in cell proliferation leading to tumor mass requires a constant blood supply. Hypoxic tumor cells are affected. Hypoxia leads to increased free radicals, stimulates the expression of HIF-1α, VEGF expression, and angiogenesis in the tumor environment. Furthermore, increased ROS leads to a reduction in intercellular adhesion and the activation of metalloproteinases involved in metastasis. This process facilitates the migration of cancer cells to other parts of the body. Thus, increases in free radicals and oxidative stress both play important roles in the development of cancer.
Keywords: Reactive oxygen and nitrogen species, antioxidant defenses, Oxidative stress.