PI3K Mutation Profiles on Exons 9 (E545K and E542K) and 20 (H1047R) in Mexican Patients With HER‐2 Overexpressed Breast Cancer and Its Relevance on Clinical–Pathological and Survival Biological Effects

Abstract

<b>Background</b>: Trastuzumab resistance is associated with overexpressing the human epidermal growth factor receptor 2 (HER-2), which results from the altered phosphoinositide 3-kinase (PI3K) pathway in breast cancer patients. <b>Objective</b>: We quantified the frequency of PI3K enzyme single and double-point mutations in Mexican patients with HER-2 overexpressing breast cancer and its association with clinical-pathological variables. <b>Methods</b>: We embedded HER-2 breast samples in paraffin from 60 patients, extracted their DNA, and evaluated PI3K mutations in 49 HER-2-positive breast tumors. We focused on mutations for one exon 20 (H1047R) and two exon 9 PI3K (E545K, E542K) hotspots and characterized them as single and double-point mutations. The mean patient follow-up was 86 months. <b>Results</b>: Of 49 patients who tested positive for HER-2 breast cancer, 14.28% showed mutations in PI3K, 71.42% single-point, and 28.56% double-point mutations. We found single-point mutations in H1047R (42.85%) and E545K (28.57%). Only two patients exhibited double-point mutations: one in E542K/E545K and another in H1047R/E545K (14.28% each). Although we observed lower survival in patients with mutations in PI3K, we did not find a significant association between these factors (<i>p</i> = 0.191). However, single and double-point mutations in PI3K were significantly associated with the clinical stages of diagnosis and tumor size (<i>p</i> = 0.027 and <i>p</i> = 0.04, respectively). <b>Conclusion</b>: Single and double-point mutations in PI3K are related to tumor size and advanced clinical-pathological traits in Mexican patients with HER-2 overexpression, and future molecular studies are necessary to understand these findings.