Precision therapy for driver gene mutations in breast cancer: Current landscape and future perspectives

Table 1 Major driver gene mutations and targeted therapy strategies in breast cancer

Gene/biomarker	Mutation type	Related pathway	Main subtype association	Targeted agent	Key clinical evidence
PIK3CA	Somatic hotspot mutations	PI3K/AKT/mTOR	HR+/HER2-	Alpelisib (PI3Kα inhibitor)	SOLAR-1 study: Significant PFS benefit[5]
ESR1	Acquired mutations	Estrogen signaling	HR+/HER2-	Elacestrant (SERD)	EMERALD study: Superior to standard endocrine therapy[6]
BRCA1/2	Germline/somatic mutations	Homologous recombination repair	TNBC, HR+/HER2-	Olaparib, talazoparib (PARP inhibitors)	OlympiAD, EMBRACA studies: PFS benefit[7,8]
AKT1	Somatic mutation (E17K)	PI3K/AKT/mTOR	HR+/HER2-	Capivasertib (AKT inhibitor)	CAPItello-291 study: Significant PFS benefit[9]
HER2 (ERBB2)	Somatic mutations	HER2 signaling	HR+/HER2- (non-amplified)	Neratinib (TKI, tyrosine kinase inhibitor)	SUMMIT basket trial: Demonstrated antitumor activity[10]

HR+: Hormone receptor-positive; HER2-: Human epidermal growth factor receptor 2-negative; PI3K: Phosphatidylinositol 3-kinase; AKT: Protein kinase B; mTOR: Mammalian target of rapamycin; SERD: Selective estrogen receptor degrader; TNBC: Triple-negative breast cancer; PARP: Poly ADP-ribose polymerase; TKI: Tyrosine kinase inhibitor; PFS: Progression-free survival.