When limited to patients treated with paclitaxel plus trastuzumab-based therapy (only trastuzumab or trastuzumab plus lapatinib)...At a median follow-up of 9 years, PIK3CA mutations were significantly associated with worse EFS in the overall cohort (hazard ratio, 2.58 [95% CI, 1.24-5.35]; P = .01), which persisted in a multivariable model including pCR, HR status, stage, and IMS (hazard ratio, 2.52 [95% CI, 1.16-5.47]; P = .02)....In this cohort study of CALGB 40601, PIK3CA mutations were significantly associated with lower pCR rates among patients receiving trastuzumab-based therapy. PIK3CA mutations were also associated with worse EFS in univariable and multivariable Cox proportional hazards regression models, which appeared to be associated with HR-positive and luminal ERBB2/HER2-positive BC.

In our study, the presence of PIK3CA mutation was significantly associated with lower pCR rates in patients treated with chemotherapy plus trastuzumab. Moreover, in uni- and multivariable Cox models, PIK3CA mutations were associated with worse long-term survival, which appeared to be driven by HR-positive and luminal HER2-positive breast tumors.

This pre-planned translational analysis aimed to identify potential early predictors for response to neoadjuvant therapy (containing T-DM1 or T) in HER2+/HR+ EBC...PIK3CA mutations were associated both directly (lower pCR) and indirectly (stagnation of CD8 change) with poorer response to neoadjuvant therapy in HER2+/HR+ EBC.