The Molecular Mechanisms Involved in Suppressing Triple Negative Breast Cancer Using Natural Agents

Introduction

Breast cancer is incessant and primary cause of death among women globally (Maurya et al., 2020). In 2018, around 2,088,849 women were affected which is about 11.6% of all cancer and among which 626,679 women died which is 6.6 percentage of all cancer deaths among women (Bray et al., 2018). Individuals in developed countries, diagnosed with breast cancer have high survival rate than breast cancer individuals in developing countries (Green and Raina, 2008). The number of breast cancer patients are two time higher in South East Asia than that of in United States. (Parkin et al., 2005). Globally, India alone accounts for 2.7% of risk of developing breast cancer along with 1.5 percentage of death risk (Monica et al., 2020). In USA, breast cancer is more observed in women whose age is in the range of 60-69 (DeSantis et al., 2019). In India, women residing in urban areas, of age between 40-45 were more prone to breast cancer, while in rural areas women of age between 60-65 were more prone to breast cancer (Chauhan et al., 2011) along with report of 26% of Northern India women diagnosed with breast cancer were below 35 years (Agarwal et al., 2007).

Breast cancer has various subtypes based on the presence or absence of progesterone receptor (PR), estrogen receptor (ER), and human epidermal growth factor-2 (HER2). Triple negative breast cancer (TNBC) is a class of breast cancer where the expression of PR, ER, and over expression of HER2 is absent (Dawood, 2010). Due to absence of receptors, TNBC is aggressive in nature and often leads to poor diagnosis resulting in lack of targeted therapies (Mersin et al., 2008). TNBC contributes approximately 10 percent of all the breast cancer (De-la-Cruz-Ku et al., 2020). Individuals with TNBC has low survival rate when compared to non-TNBC (Onitilo et al., 2009). Women under the age of 40 are more prone to TNBC. There is a two-fold higher risk of TNBC in women under the age of 40 when compared to women over age of 50 (Trivers et al., 2009). It is reported that in India, TNBC is more common and has higher incidence when compared to western population (Sandhu et al., 2016). Based on differentiation stages and expression of cell marks, TNBC are classified into three sub groups which is molecular apocrine, claudin low and basal like cells. The molecular apocrine subgroup is found in progressive stages and most differentiated subgroup accounting for 0.5 to 4 percentage of TNBC with characteristics such as absence of ER, PR and HER2 with presence of androgen receptor. Basal like subgroup accounts for 75 percentage of TNBC which lacks DNA repair and overexpression of EGFR (Ma et al., 2010). Claudin subgroup of TNBC consists of poorly differentiated mesenchymal stem cells along with characteristics of CD⁴⁴⁺/CD^24- and upregulation of mesenchymal markers that played an important role in tumour return (Kwon, 2013). TNBC are further classified into six subtypes based on gene expression, which are basal like 1 (BL1), basal like 2 (BL2), immunomodulatory (IM), mesenchymal (M), mesenchymal stem like (MSL), luminal androgen receptor (LAR) which is characterized based on androgen receptor signaling (Hubalek et al., 2017; Lehmann et al., 2011)