Table 2.

Examples of mutation-matched therapies for breast cancer

Altered genes with predictive biomarker potentialTreatment approachStrength of hypothesis for somatic alteration-targeted drug match (reference)
HER2 amplificationHER2-directed antibodies and HER2 kinase inhibitors1
Trastuzumab, pertuzumab, and lapatinib. All approved agents
PIK3CA mutationPIK3CA-selective inhibitors2
Phase I BYL719 (18)
FGFR1 amplification, FGF3 amplification, other FGF ligands and receptors, and rare receptor mutationsFGFR small-molecule inhibitors and antibodies2
Phase I BGJ398 (48) and phase I E3800 (47)
Inherited and somatic BRCA1 and BRCA2 mutationPARP inhibitors2
Olaparib (49) and veliparib: NCT01506609a
Cyclin D1/CDK4/CDK6 amplification or deletion o f CDKN1B, CDKN2A, and CDKN2BCDK4/6 inhibitors2
PD0332991 (40)
AKT1-3 gain-of-function mutation/gene fusion via translocation/amplificationAKT inhibitors3
MK-2206: NCT01277757a
GATA3 mutationAromatase inhibition3
Retrospective analysis of Z1031 (4)
PTEN/INPP4B loss-of-function mutation/deletion/loss of expression in TNBCBroad-spectrum PI3K pathway inhibitors3
BKM120: NCT01629615a
MDM2 amplification in TP53 wild-type tumorsMDM2 inhibitors3
RO5503781: NCT01462175a
HER2 mutationSmall-molecule HER2 kinase inhibitors3
Neratinib: (NCT01670877)a (50)
PIK3R1 loss-of-function mutationPI3K pathway inhibitors?4
MLL family member mutationHDAC inhibition?4
Rare RTK mutationsVarious matched inhibitors?4

NOTE: Number 1 indicates approved therapy; 2, early evidence of efficacy; 3, clinical investigations under way; and 4, clinical investigations not yet activated.

  • aClinical number. The trials mentioned in this table are examples, and the list is not meant to be comprehensive.