PIK3CA Mutations Are Associated With Lower Rates of Pathologic Complete Response to Anti–Human Epidermal Growth Factor Receptor 2 (HER2) Therapy in Primary HER2-Overexpressing Breast Cancer

摘要: Purpose Phosphatidylinositol 3-kinase (PI3K)/AKT pathway aberrations are common in breast cancer, with mutations PIK3CA being the most common. This study investigated association between genotype and pathologic complete response (pCR) rates human epidermal growth factor receptor 2 (HER2) ‐positive cancer treated either dual or single anti-HER2 treatment addition to neoadjuvant chemotherapy. Patients Methods 504 tumor samples from participants GeparQuattro, GeparQuinto, GeparSixto studies were evaluated. All HER2-positive patients received trastuzumab lapatinib combination plus anthracycline-taxane evaluated formalin-fixed, paraffin-embedded tissues core biopsies a cell content of 20% by using classical Sanger sequencing exon 9 20. Results Overall, 21.4% harbored mutation. Detection mutation was significantly associated lower pCR rate (19.4% v 32.8% wild-type; odds ratio [OR], 0.49; 95% CI, 0.29 0.83; P .008). In 291 hormone (HR) tumors, 11.3% compared 27.5% wild-type (OR, 0.34; 0.15 0.78; .011). 213 HR-negative 30.4% 40.1% without 0.65; 0.32 1.32; .233; interaction test .292). multivariable analysis, HR status provided independent predictive information. mutation, 16%, 24.3%, 17.4% lapatinib, trastuzumab, combination, respectively (P .654) group, they 18.2%, 33.%, 37.1%, .017). Disease-free survival overall not statistically different mutant PIK3CA. Conclusion carcinomas less likely achieve after anthracycline-taxane‐based chemotherapy treatment, even if is given. J Clin Oncol 32:3212-3220. © 2014 American Society Clinical Oncology