An integrative analysis of PIK3CA mutation, PTEN, and INPP4B expression in terms of trastuzumab efficacy in HER2-positive breast cancer

摘要: The phosphoinositide-3-kinase (PI3K) pathway is commonly deregulated in breast cancer through several mechanisms, including PIK3CA mutation and loss of phosphatase tensin homolog (PTEN) inositol polyphosphate 4phosphatase-II (INPP4B). We aimed to evaluate the predictive relevance these biomarkers trastuzumab efficacy HER2-positive disease. evaluated effect 43 patients with HER2-overexpression who received neoadjuvant treatment. was examined by direct sequencing digital PCR assay, copy number assessed assay pretreatment tissues. PTEN, pAkt, INPP4B were immunohistochemistry. Direct detected mutant DNA 21% all patients, but incidence increased 49% using PCR. pathological complete response (pCR) rate mutations 29% compared 67% for those without (P50.093), when defined as positive if proportion more than 10% total genetic content Low PTEN expression associated less pCR high (33% versus 72%, P50.034). There no significant associations number, pAKt, or efficacy. In multivariate analysis, activation PI3K due either low related poorer (OR 0.11, 95%CI; 0.03–0.48). conclusion, activating trastuzumab-based treatment cancer. Combined analysis