Tumor PIK3CA mutations, lymphocyte infiltration, and recurrence-free survival (RFS) in early breast cancer (BC): Results from the FinHER trial.

507 Background: Tumor PIK3CA mutations (mts) and lymphocyte infiltration (LI) are prognostic in BC, but their importance is unknown in HER2-positive (HER2+) BC treated with adjuvant trastuzumab (T). Methods: The FinHER trial randomized 1010 patients (pts) with pN+ or high-risk pN- BC to 3 cycles of docetaxel (D) or vinorelbine, followed by 3 cycles of FEC. Pts with HER2+ BC were further randomized to 9 weeks of T or no T (n=232). Pts treated with D and T had superior outcome in prior analyses. BC samples were subjected to somatic hotspot mt profiling (Sequenom) and quantification of percentage tumor LI using full-face H&E sections. RFS and interactions with T were explored with Kaplan-Meier and Cox regression analyses. Results: The median FU time was 62 months. 935 (92.6%) and 687 (68.1%) tumors underwent LI and mt analysis, respectively. Correlation of LI assessment between 2 pathologists was 0.78 (p<0.001). 54 mts detected in 13 genes were evaluated. PIK3CA mts (exons 1,2,9,13,18,20) was present in 25.3% (n=174) and ERBB2 mt in 4.5% (n=31) BCs. Only 1 AKT mt was found and none in KRAS, BRAF, NRAS or PTEN. In ER+/HER2-, HER2+ and ER-/HER2- subtypes the prevalence of PIK3CA mts was 30.2%, 19.5% and 9.2%; ERBB2 mt 6.3%, 1.9% and 2.6%, respectively (both p<0.05). Neither PIK3CA nor ERBB2 mts were associated with RFS overall or within BC subgroups. No interaction was found for the benefit with T and presence of PIK3CA mt in HER2+ BC (interaction p=0.17 T vs no T). Increasing LI was associated with favorable RFS in ER-/HER2- BC (continuous score adjusted p=0.032); 3-y RFS was 90% with extensive LI (>30% infiltrated) vs 66% with non-extensive LI (p=0.007). In HER2+ BC, whilst there was no association with prognosis overall, there was a significant interaction with the benefit from T vs. no T and increasing LI (continuous score interaction p=0.042) with 3-yr RFS 96% vs 78% for extensive and non-extensive LI treated with T respectively (p=0.014). Conclusions: We report 3 clinically relevant findings from this large clinical trial dataset: 1) PIK3CA mts were not prognostic; 2) LI is a strong prognostic factor in ER-/HER2- BC and 3) for the first time that extensive LI predicts benefit from adjuvant T.