In the second case, MBCB007 (Fig 4C), who was initially diagnosed with ER+/HER2- metastatic disease via routine tumour biopsy immunohistochemistry (IHC) and in situ hybridization (S6A Fig and S6B Fig), we detected emergence of a subclone harbouring ERBB2 amplification through LC-WGS of ctDNA following treatment with a CDK4/6 inhibitor in combination with letrozole (Fig 4D). Here, ESR1 is linked to neoplasm.