Abstract
In breast cancer, HER2 receptor over expression is associated with aggressive phenotype and poor prognosis. Trastuzumab, a monoclonal antibody against HER2, accrues significant clinical benefit in the metastatic and adjuvant settings. However, only 20% of patients are found positive for HER2-overexpression (HER2-positive) and receive Trastuzumab. Moreover, activating mutations in HER2 gene that play a key role in tumorigenesis are sparsely studied. Herein we perform a genetic study of the HER2 tyrosine kinase domain (TKD) in HER2-negative breast cancer patients. 50 formalin-fixed and paraffin-embedded tissues of breast cancer were assessed for expression of HER2 receptor by immune histochemistry (IHC). HER2-negative tumors were subjected to DNA sequencing to detect potential activating mutations in the TKD of HER2 gene. Twenty seven tumors were revealed with IHC score 0 or 1+ and classified as HER2-negative. Through Sanger sequencing of the exons 18-22, two heterozygote variants V750L and A751S located at exon 19 were detected in tumor tissue of one patient among 27 explored. The detected variants, not previously reported, need confirmation and to be classified as either somatic or germline. Exploration of larger cohort would be necessary to draw strong conclusions.