Outcome impact of PIK3CA mutations in HER2-positive breast cancer patients treated with trastuzumab

Background: Phosphatidylinositol 3-kinase (PI3K) pathway activation has been suggested to negatively influence response to anti-HER2 therapy in breast cancer patients. The present study focused on mutations of the PIK3CA gene, encoding one of the two PI3K subunits. Methods: PIK3CA mutations were assessed by direct sequencing in 80 HER2-positive patients treated with 1 year of trastuzumab. All patients preoperatively received four cycles of anthracycline-based chemotherapy, followed by four cycles of docetaxel and 1 year of trastuzumab, starting either before surgery with the first cycle of docetaxel and continuing after surgery (neoadjuvant trastuzumab arm, n =43), or only after surgery (adjuvant trastuzumab arm, n =37). Results: PIK3CA mutations were found in 17 tumours (21.3%). Better disease-free survival (DFS) was observed in patients with PIK3CA wild-type compared with mutated tumours ( P =0.0063). By combining PIK3CA status and treatment arms, four separate prognostic groups with significantly different DFS ( P =0.0013) were identified. Conclusion: These results confirm that the outcome of HER2-positive patients treated with trastuzumab is significantly worse in patients with PIK3CA- mutated compared with wild-type tumours.