BRAF V600E mutation detected using ARMS-PCR technology in Iraqi Women Patients with Breast Cancer treated with Vemurafenib

Background: Breast cancer is the most common cancer in Iraqi women and often has an aggressive biological phenotype, occurring at a relatively young age. Introduction: Despite the importance of their clinical utility, most common somatic alterations in melanoma and colorectal cancer Such as mutations affecting BRAFV600EA group BRAF mutation p.Val600Glu (p.V600E) questions how often or significant these BRAF mutations BRAF act as robust biomarkers for breast carcinoma especially in studies in Middle Eastern populations such as those being studied here.,32684197. Selective small-molecule inhibitors against BRAF mutated tumors, including Vemurafenib, are emerging as promising new opportunities for targeted therapy. Objective: To conduct a pilot study that screens for BRAF p.Val600Glu mutation in germline/somatic mutations from a small population of patients (n100) with progressive AdvancedAnalysis of the status of B-Raf mutations and clinical response profiles to vemurafenib therapy in a cohort of Iraqi women breast cancer patients using Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR) Methods: Genomic DNA was extracted from hundred (100) FFPE tissue and matching peripheral blood samples. An ARMS-PCR assay was designed using allele-specific inner primers composed of a 3-prime terminus mismatch, which provided highly sensitive and specific discrimination between the c.1799T>A nucleotide substitution. PCR products were confirmed by subjecting 2% agarose gel electrophoresis. Patients with confirmed mutations were treated with vemurafenib tailored to the mutation and monitored for objective clinical response. Results: Among 100 patients screened by ARMS-PCR, only thirteen (13%) tested positive for the BRAF p.Val600Glu mutation. mutation-positive cases had aggressive, poorly differentiated TNBC subtypes. We initiated therapy and all patients demonstrated an initial partial response and stabilization of disease to Vemurafenib, but had progressive disease at < 6 months in a manner consistent with known feedback-loop pathways including EGFR reactivation. Conclusion: The BRAF p.Val600Glu mutation is an infrequent but clinically relevant oncogenic driver in a subset of aggressive Iraqi breast cancers. ARMS-PCR is a powerful, rapid and low-cost molecular diagnostic technique for high-throughput mutational screening. Epithelial breast tumors can be resistant to single-agent Vemurafenib; therefore a combination therapeutic regimen should be tested.