Fig. 3

Dual MAP3K1 and PIK3CA alterations are associated with a highly luminal A like phenotype and luminal A status is associated with clinical benefit to PI3Ki with endocrine therapy. a RNAseq data from TCGA breast cancers (n = 959) were stratified by MAP3K1 and PIK3CA status and used to determine correlation to Luminal A and Luminal B centroids using the genefu package in R. Difference in correlation to both centroids were compared using a paired T-test. MAP3K1/PIK3CA altered tumors demonstrated a significantly higher association with Luminal A centroids than Luminal B centroids ***P < 0.0001 by two-sample two-tailed t-test. Error bars represent mean ± SEM. b PAM50 analysis was performed using a custom NanoString RNA panel on a subset of samples (based on tissue availability) in tumors from patients enrolled in buparlisib + letrozole²⁵ or alpelisib + letrozole²¹ (n = 14 and n = 12, respectively). All samples predicted as luminal A or B. Mutation status is denoted by color of data points. In the combined analysis, luminal A tumors showed a trend for enrichment of patients achieving clinical benefit (CR/PR or SD > 6 months) by a Fisher’s exact test (p = 0.07)