Abstract S4-06: PIK3CA mutation predicts resistance to anti-HER2/chemotherapy in primary HER2-positive/hormone-receptor-positive breast cancer – Prospective analysis of 737 participants of the GeparSixto and GeparQuinto studies

摘要: Background: Phosphatidylinositol 3-kinase (PI3K)/AKT pathway aberrations are common in breast cancer (BC), PIK3CA mutations being the most common. Mutations frequently found hot-spots located helical and kinase domains (exons 9 20). Reported data is discrepant with regard to prognostic or predictive value of especially HER2+ve BC. We therefore investigated frequency associations triple negative (TN) primary BC by treated neoadjuvant therapy. Methods: prospectively evaluated 512 participants Geparsixto (G6) study (von Minckwitz et al. ASCO 2013) validated 225 GeparQuinto (G5) (Untch 2012). The G6 investigates effect adding carboplatin a non-pegylated liposomal doxorubicin/taxane combination for treatment patients TN All received trastuzumab lapatinib, bevacizumab. G5 showed that added EC-Doc results significantly higher pCR rate than lapatinib. HER2, hormone receptors (HR), Ki67 were centrally assessed both studies. was genotyped tumor material from formalin-fixed, paraffin embedded core biopsies taken before therapy cell content ≥20% using classical Sanger sequencing exon 20. Results: In study, 595 have been randomized 09/2011 11/2012. Median age 47 years (range 21-78); tumors cT2 (65%); cN0 (57%); ductal invasive (93%), grade 3 within group 62% HR-positive. Currently, genotype available - 240 272 disease. Overall, 13.1% at least one mutation, HER2+ve: 19.2% TNBC: 7.7%. numerically more frequent HER2+ve/HR+ve compared HER2+ve/HR-ve group: 21.5% vs 15.4% respectively (p = 0.245. lower mutant wt (22.7% vs. 43.6%; p 0.001).This only significant (17.8% 36.8%; 0.015) TNBC (33.3% 49%; 0.168). Within HER2+ve/HR+ subgroup pts had 6.5% 30.8% 0.005). contrast there no difference (42.9% 46.1%) according mutation status 0.825) group. 620 biomaterial genotyping central confirmation HER2 hormone-receptor status. analyses ongoing lapatinib cohorts will be presented meeting. Conclusion: Pts resistant chemotherapy dual anti-HER2 treatment. Other options needed tested this project has funded EU-FP7 RESPONSIFY No 278659. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr S4-06.