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HER2 is a member of the human epidermal growth factor receptor (HER/EGFR/ERBB) family. But contrary to other members of the ERBB family, HER2 does not directly bind ligand. HER2 activation results from heterodimerization with another ERBB member or by homodimerization when HER2 concentration are high, for instance in cancer. [8]
The overexpression of HER2 is determined by immunohistochemistry (IHC), or with fluorescent in situ hybridization in those equivocal cases where IHC does not provide a clear result. Different molecular subtypes of breast cancer have also been described, which loosely align with receptor status: Luminal A (ER and/or PR positive; HER2 negative)
Cells with none of these receptors are called basal-like or triple negative. HER2-low has some HER2 proteins on the cell surface, but not enough to be classified as HER2-positive. [4] Trastuzumab deruxtecan is the first approved therapy by the US Food and Drug Administration (FDA) targeted to people with the HER2-low breast cancer subtype. [4]
The epidermal growth factor receptor is a member of the ErbB family of receptors, a subfamily of four closely related receptor tyrosine kinases: EGFR (ErbB-1), HER2/neu (ErbB-2), Her 3 (ErbB-3) and Her 4 (ErbB-4). In many cancer types, mutations affecting EGFR expression or activity could result in cancer. [6]
The HER2 gene (also known as HER2/neu and ErbB2 gene) is amplified in 20–30% of early-stage breast cancers. [43] Trastuzumab is a monoclonal antibody targeting HER2, inducing an immune-mediated response that causes internalization and recycling of HER2. It may also upregulate cell cycle inhibitors such as p21 Waf1 and p27 Kip1. [57]
Triple-negative breast cancer (TNBC) is any breast cancer that either lacks or shows low levels of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) overexpression and/or gene amplification (i.e. the tumor is negative on all three tests giving the name triple-negative). [1]
All four ErbB receptor family members are nearly same in the structure having single-chain of modular glycoproteins. [4] This structure is made up of an extracellular region or ectodomain or ligand binding region that contains approximately 620 amino acids, a single transmembrane-spanning region containing approximately 23 residues, and an intracellular cytoplasmic tyrosine kinase domain ...
Fulvestrant, sold under the brand name Faslodex among others, is an antiestrogenic medication used to treat hormone receptor (HR)-positive metastatic breast cancer in postmenopausal women with disease progression as well as HR-positive, HER2-negative advanced breast cancer in combination with abemaciclib or palbociclib in women with disease progression after endocrine therapy. [2]
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