Table 1. Genetic alterations in ctDNA associated with resistance to anti-HER2 therapy.

Patient ID	Resistance	Gene	Mutation (CDS)	Mutation (Amino Acid)	Oncogenic alteration in COSMIC database
5	Primary	PIK3CA	c.[3140A>G]	p.[H1047R]	Yes
		ERBB2	c.[3235G>A]	p.[E1079K]	Yes
		MTOR	c.[6286G>C]	p.[D2096H]	—
		ERBB2	Amplification	—	Yes
		CDK12	Amplification	—	Yes
		TP53	c.[811G>T]	p.[E271*]	Yes
8	Primary	ERBB2	Amplification	—	Yes
		ROS1	c.[6316G>A]	p.[A2106T]	Yes
9	Primary	ATM	c.[8246A>T]	p.[K2749I]	—
		TP53	c.[392A>G]	p.[N131S]	Yes
		NOTCH1	c.[4319_4320insC]	p.[I1440fs*?]	—
11	Primary	ERBB2	Amplification	—	Yes
		CDK12	Amplification	—	Yes
		MED12	c.[3745C>A]	p.[L1249I]	—
		MSH2	c.[1742T>G]	p.[I581S]	—
12	Primary	ERBB2	Amplification	—	Yes
		TP53	c.[706T>A]	p.[Y236N]	Yes
14	Primary	PIK3CA	c.[1035T>A]	p.[N345K]	Yes
		CCND1	Amplification	—	—
		FGF19	Amplification	—	—
		FGF3	Amplification	—	—
		FGF4	Amplification	—	—
		GPR124	Amplification	—	—
2	Acquired	CROT	c.[1152A>C]	p.[K384N]	—
		ERBB2	Amplification	—	Yes
		CDK12	Amplification	—	Yes
		DOT1L	c.[967G>A]	p.[E323K]	—
3	Acquired	PIK3CA	c.[3140A>G]	p.[H1047R]	Yes
		ERBB2	Amplification	—	Yes
		CDK12	Amplification	—	Yes
		TP53	c.[375+2T>G]	—	Yes
4	Acquired	PIK3CA	c.[3140A>G]	p.[H1047R]	Yes
		TP53	c.[318C>G]	p.[S106R]	Yes
6	Acquired	RPS14	c.[218C>A]	p.[A73D]	—
7	Acquired	ERBB2	Amplification	—	Yes
		TP53	c.[497C>G]	p.[S166*]	Yes
15	Acquired	MTOR	c.[1077C>A]	p.[S359R]	—
17	Acquired	TP53	c.[672+1G>T]	—	Yes
		PIK3CA	c.[1637A>G]	p.[Q546R]	Yes
		TP53	c.[833C>G]	p.[P278R]	Yes
		ERBB2	Amplification	—	Yes
		PIK3CA	c.[3140A>G]	p.[H1047R]	Yes
18	Acquired	ERBB2	c.[2264T>C]	p.[L755S]	Yes
		PTEN	c.[511C>T]	p.[Q171*]	Yes
		PIK3CA	c.[1624G>A]	p.[E542K]	Yes