Table 1.

Classifications according to potentially targetable pathways based on exome or targeted sequencing

TCGA (basal-like; ref. 36)Genomic alteration (frequency, %)
p53 pathwayTP53 mut (84), gain of MDM2 (14)
PI3K/PTEN pathwayPTEN mut/loss (35), INPP4B loss (30), PIK3CA mut (7)
RB1 pathwayRB1 mut/loss (20), CCNE1 amp (9), high expression of CDKN2A, low RB1 expression
METABRIC (ER-negative; ref. 37)Mutated gene (frequency, %)
AKT signalingPIK3CA (24), AKT1 (2), PTEN (4), PIK3R1 (3), FOXO3 (1)
Cell-cycle regulationRB1 (4), CDKN2A (1)
Chromatin functionKMT2C (9), ARID1A (3), NCOR1 (2), PBRM1 (3), KDM6A (2)
DNA damage and apoptosisTP53 (77), BRCA1 (3), BRCA2 (3)
MAPK signalingNF1 (4), MAP3K1 (3), MAP2K4 (1), KRAS (1)
Tissue organizationCDH1 (3), MLLT4 (3)
Transcription regulationTBX3 (2), RUNX1 (2), GATA3 (1), ZFP36L1 (1), MEN1 (1)
UbiquitinationUSP9X (3), BAP1 (3)
OtherERBB2 (3), SMAD4 (1), AGTR2 (1)
Residual disease post–neoadjuvant chemotherapy (triple-negative; ref. 39)Genomic alteration (frequency, %)
Cell cycleRB1 loss (11), CDKN2A loss (9), CDKN2B loss, CDK4 amp, CDK6 amp (6), CCND1 amp (6), CCND2 amp (6), CCND3 amp (6), CCNE1 amp (6), AURKA amp
PI3K/mTOR pathwayPTEN mut/loss (16), PIK3CA mut/amp (12), PIK3R1 mut/amp, AKT1 amp, AKT2 amp, AKT3 amp (7), RAPTOR amp, RICTOR amp, TSC1 truncations/mut
Growth factor receptorIGF1R amp (6), EGFR amp (4), MET amp, KIT amp, FGFR1 amp, FGFR2 amp, FGFR4 amp
RAS/MAPK pathwayKRAS amp/gain (7), BRAF amp/gain, RAF1 amp/gain, NF1 truncations (7)
DNA repairBRCA1 truncations/loss/mut (11), BRCA2 truncations/loss/mut, ATM mut
JAK2/STAT3 pathwayJAK2 amp (10)
  • NOTE: Mut, gene mutation; gain, gene copy-number gain (<5 but more than 2 copies); amp, gene amplification (≥5 copies and/or gene-specific and centromeric probe ratio >2). The definition of copy-number gain vs. amplification is partly platform and study dependent. In general, copy-number gain ≥5 is considered an amplification, whereas copy-number gain >2 but below 5 is considered a copy-number gain. However, some studies define amplification when gene-specific vs. centromeric probe ratio is >2. Frequencies (%) of alterations are included when available.