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

• Published in: International journal of breast cancer 2024, Vol.2024 (1), p.9058033
• Main Authors: Nieto-Coronel, T, Alette, Ortega-Gómez, Yacab, R, Fernández-Figueroa, E A, Lopez-Camarillo, C, Marchat, L, Astudillo-de la Vega, H, Ruiz-Garcia, E
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Binding sites; Breast cancer; Cell growth; Clinical outcomes; Cloning; Enzymes; Epidermal growth factor; ErbB-2 protein; Estrogens; Ethylenediaminetetraacetic acid; Exons; Gene mutations; Genetic aspects; Growth factors; Kinases; Lymphatic system; Medical prognosis; Mutation; Patients; Proteins; Tumors; Type 2 diabetes; Womens health
• ISSN: 2090-3170; 2090-3189; 2090-3189
• DOI: 10.1155/2024/9058033

: 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. : 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. : 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. : 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 ( = 0.191). However, single and double-point mutations in PI3K were significantly associated with the clinical stages of diagnosis and tumor size ( = 0.027 and = 0.04, respectively). : 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.