Abstract 1220: <i>PIK3CA</i> mutations in primary HER2-positive and triple negative breast cancer.
Authors: Sibylle Loibl, Carsten Denkert, Sherene Loi, Fabrice Andre, Annika Lehmann, Andreas Schneeweiss, Jens Uwe Blohmer, Christian Jackisch, Stephan Gade, Peter Fasching, Christian Schem, Christos Sotiriou, Michael Untch, Gunter von Minckwitz
Journal: Cancer Research (2013)

Abstract Background: Phosphatidylinositol 3-kinase (PI3K)/AKT pathway aberrations are common in breast cancer. PIK3CA mutations are the most frequent ones in breast cancer. Mutations were most frequently found in exons 9 and 20. Reported data is discrepant with regard to prognostic or predictive value of PIK3CA mutations especially in HER2+ve breast cancer. We therefore investigate PIK3CA mutations in HER2+ve and triple negative (TN) primary breast cancer (BC) and correlate the mutations with pathological complete response (pCR) after neoadjuvant therapy. Methods: We prospectively evaluated PIK3CA mutations in the 600 participants of the neoadjuvant Geparsixto study (NCT01426880). The study investigates the effect of adding carboplatin to a liposomal doxorubicin/taxane combination for the treatment of patients with HER2+ve and TN primary BC. HER2+ve patients received concomitantly trastuzumab and lapatinib, the TN patients bevacizumab. HER2, hormone receptors (HR), and Ki67 were centrally confirmed. PIK3CA genotyped in tumor material from formalin fixed, paraffin embedded core biopsies before therapy using classical Sanger sequencing of exon 9 and 20. Results: From September 2011 to November 2012, 600 patients with centrally confirmed HER2+ve or TN primary BC have been included in the Geparsixto study. Median age was 46 years (range 21-78); most tumors were cT2 (66%); cN0 (60%); ductal invasive (92%), grade 3 (65%); within the HER2+ve group 62% were HR positive. So far, in 344 randomized patients PIK3CA mutations have been evaluated, 155 with HER2+ve and 189 with TN disease. Overall at least one mutation could be detected in 17.9%; in 19.4% of the HER2+ve and 6.3% of the TN BC. An exon 9 mutation could be detected in 7.8% of the HER2+ve and 3.2 of the TNBC cases and an exon 20 mutation in 12.6% of the HER2+ve and 4.2 of the TN cases. A mutation in both exons was detectable in one case only. PIK3CA mutations were more frequent in the HER2+ve/HR+ve group 22.9% vs 13.6% in the HER2+ve/HR-ve group. Conclusion: PIK3CA mutations are more frequent in HER2+ve than in TN BC which is in line with previous reports. Results on all 600 patients and correlation with pCR in the two subgroups will be presented at the meeting. The project has been funded within the EU-FP7 project RESPONSIFY No 278659. Citation Format: Sibylle Loibl, Carsten Denkert, Sherene Loi, Fabrice Andre, Annika Lehmann, Andreas Schneeweiss, Jens Uwe Blohmer, Christian Jackisch, Stephan Gade, Peter Fasching, Christian Schem, Christos Sotiriou, Michael Untch, Gunter von Minckwitz. PIK3CA mutations in primary HER2-positive and triple negative breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1220. doi:10.1158/1538-7445.AM2013-1220