Somatic Mutations in HER2 and Implications for Current Treatment Paradigms in HER2-Positive Breast Cancer.

Somatic Mutations in HER2 and Implications for Current Treatment Paradigms in HER2-Positive Breast Cancer. J Oncol. 2020;2020:6375956 Authors: Gaibar M, Beltrán L, Romero-Lorca A, Fernández-Santander A, Novillo A Abstract In one of every four or five cases of breast cancer, the human epidermal growth factor receptor-2 (HER2) gene is overexpressed. These carcinomas are known as HER2-positive. HER2 overexpression is linked to an aggressive phenotype and a lower rate of disease-free and overall survival. Drugs such as trastuzumab, pertuzumab, lapatinib, neratinib, and the more recent afatinib target the deregulation of HER2 expression. Some authors have attributed somatic mutations in HER2, a role in resistance to anti-HER2 therapy as differential regulation of HER2 has been observed among patients. Recently, studies in metastatic ER + tumors suggest that some HER2 mutations emerge as a mechanism of acquired resistance to endocrine therapy. In an effort to identify possible biomarkers of the efficacy of anti-HER2 therapy, we here review the known single-nucleotide polymorphisms (SNPs) of the HER2 gene found in HER2-positive breast cancer patients and their relationship with clinical outcomes. Information was recompiled on 11 somatic HER2 SNPs. Seven polymorphisms are located in the tyrosine kinase domain region of the gene contrasting with the low number of mutations found in extracellular and transmembrane areas. HER2-positive pa...
Source: Journal of Oncology - Category: Cancer & Oncology Tags: J Oncol Source Type: research