Background: TNBC cell lines characterized as mesenchymal (M) and luminal androgen receptor (LAR) commonly have aberrations in the PI3K pathway. However, the incidence in human tumors and impact on response to therapy is less clear. Methods: Pre-treatment biopsies were collected from TNBC patients (pts) prior to NACT. Tumors were categorized into 5 groups using the Pietenpol criteria (Lehmann JCI 2011): basal-like (BL) comprised of BL-1 and BL-2, M comprised of M and mesenchymal stem-like, immunomodulatory (IM), LAR, or unspecified (UNS). Using RNAseq data, variants were identified in 16 PI3K pathway genes: AKT1, AKT2, AKT3, CRKL, IRS2, MTOR, PIK3CA, PIK3CG, PIK3R1, PTEN, RICTOR, RPTOR, RNF43, TSC1, TSC2. Results: Data was available in 63 pts (N = 4 stage I; N = 41 stage II; N = 18 stage III). There was no significant association between stage and subtype. 67 PI3K pathway variants were identified in 39 (62%) tumors. The incidence of mutated tumors and their differential response to NACT defined by residual cancer burden (RCB) in each subtype is presented in the table. There was no significant association between subtype and incidence of mutated tumors (P = 0.10). However, there were more mutated tumors in the LAR compared to non-LAR subsets (100% vs 57%); the majority of LAR tumors (5/7) had a variant in the PIK3R1 gene. The incidence of mutated tumors in the M vs non-M subsets was similar (57% vs 63%). Pts with mutated tumors did not have a significantly worse response to NACT overall (46% vs 54%; P = 0.61) or within the M subset (25% vs 50%; P = 0.58). Conclusions: In this cohort of TNBC pts, the incidence of PI3K pathway aberrations was higher than previously reported, likely due to the comprehensive genes evaluated. There was no significant difference in incidence of aberrations across subtypes, and PI3K pathway aberration was not associated with altered response to NACT. Larger cohorts are needed to clarify the impact of PI3K pathway aberrations in TNBC subtypes.