Title: Breast Cancer Is Globally Emerging Challenging: Epidemiology, Pathogensis and Therapeutic Approach (Enzymatic and Non-Enzymatic Antioxidant) –A Review

Abstract

Breast cancer (BC) stands as the most predominant neoplastic growth worldwide, representing a significant global health challenge. With 7.8 million women diagnosed by the end of 2020 and 2.29 million new cases reported in 2022, breast cancer accounts for approximately 11.5% of all cancer diagnoses globally. While developed countries report higher incidence rates, low- and middle-income countries, including Pakistan, face disproportionately high mortality rates due to delayed diagnosis, limited access to effective therapies, and inadequate healthcare facilities. This review comprehensively examines the epidemiology, pathogenesis, risk factors, and therapeutic approaches for breast cancer, with particular emphasis on the role of oxidative stress and antioxidant systems. The pathogenesis of breast cancer involves complex mechanisms including genetic alterations (BRCA1/2 mutations, PIK3CA, TP53), hormonal homeostasis disturbances, and immune interference within the tumor microenvironment. Oxidative stress, generated from endogenous and exogenous sources, plays a dual role in carcinogenesis—promoting tumor development when antioxidant systems are insufficient while potentially inducing apoptosis at controlled levels. The cellular antioxidant defense system comprises enzymatic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, thioredoxin reductase, and peroxiredoxin) and non-enzymatic antioxidants (glutathione, thioredoxin, vitamins A, C, D, and E, along with micronutrients including zinc, magnesium, and selenium). Emerging evidence suggests that these antioxidants exhibit potential anticancer properties through various molecular mechanisms. Furthermore, nanotechnology-based drug delivery systems, including lipid-based nanocarriers and polymeric nanoparticles, offer promising strategies for targeted antioxidant delivery, enhancing bioavailability and therapeutic efficacy. This review highlights the critical value of developing preventive, protective, and treatment strategies against breast cancer, particularly in resource-limited settings, while exploring the therapeutic potential of antioxidant-based approaches in breast cancer management.