BREAST CANCER: INSIGHTS INTO THE MAJOR SIGNALING PATHWAYS IMPLICATED IN MOLECULAR PATHOGENESIS -

As the most commonly occurring cancer in women worldwide, breast cancer poses a formidable public health challenge on a global scale. Breast cancer encompasses of a group of biologically and molecularly heterogeneous diseases originated from the breast. Regarding gene profile studies, breast cancer can be categorized, according to the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor (HER)-2 expression, into five molecular subtypes: luminal A, luminal B, HER2-overexpressing, triple negative and normal-like breast cancer. ER pathway plays prominent roles in development and progression of carcinogenesis by preventing apoptosis especially in ER+ breast cancer. In addition, breast cancer proliferation is enhanced by epidermal growth factor (EGF), which stimulates signaling through the PI3K/AKT/mTOR and RAS/RAF/MEK/ERK pathways by activation of the epidermal growth factor receptor (EGFR) axes. These pathways are tightly interconnected with ER-activated signaling and multiple points of cross talks are now elucidated. The latent relevance of ER, PI3K/AKT/mTOR and Raf/ MEK/ERK signaling pathways to all major subtypes of breast cancer will be discussed in this review.