PIK3CA mutations in primary HER2-positive and triple negative breast cancer.

Abstract

11061 Background: Phosphatidylinositol 3-kinase (PI3K)/AKT pathway aberrations are common in breast cancer (BC), PIK3CA mutations being the most common. Mutations are frequently found in hot-spots located in the helical and kinase domains (exons 9 and 20). Reported data is discrepant with regard to prognostic or predictive value of PIK3CA mutations especially in HER2+ve BC. We therefore investigated the frequency and prognostic associations of PIK3CA mutations in HER2+ve and triple negative (TN) primary BC by treated with neoadjuvant therapy. Methods: We prospectively evaluated PIK3CA mutations in the 595 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. All HER2+ve patients received trastuzumab and lapatinib, the TN patients received bevacizumab. HER2, hormone receptors (HR), and Ki67 were centrally assessed. PIK3CAwas genotyped in tumor material from formalin-fixed, paraffin embedded core biopsies taken before therapy using classical Sanger sequencing of exon 9 and 20. Results: From 09/2011 to 11/2012, 595 patients with HER2+ve or TN primary BC have been randomized in the Geparsixto study. Median age was 47 years (range 21-78); most tumors were cT2 (65%); cN0 (57%); ductal invasive (93%), grade 3 (65%); within the HER2+ve group 28% were HR positive. So far, PIK3CA genotype was evaluated in 395 randomized patients - 176 with HER2+ve and 219 with TN disease. Overall, 11.1% were found to have at least one mutation, in HER2+ve: 18.2% and TN BC: 5.5%. An exon 9 mutation was detected in 6.3% of the HER2+ve and 2.7% of the TNBC cases and an exon 20 mutation in 11.9% of the HER2+ve and 3.6% of the TN cases. A mutation in both exons was detected in 2 TN cases. PIK3CAmutations were more frequent in the HER2+ve/HR+ve compared to the HER2+ve/HR-ve group: 22.8% vs 10.6% respectively (p=0.047). Conclusions: PIK3CAmutations are more frequent in HER2+ve then in TN BC which is in line with previous reports. Results on all 595 patients and the correlation with response to therapy (pCR) will be presented at the meeting. The project has been funded within the EU-FP7 project RESPONSIFY No 278659. Clinical trial information: NCT01426880.