Taken together, this constellation of findings suggests that in this patient 1) selection occurred via dissemination of a rare primary tumor subclone (2% of tumor cells) that had sequentially acquired two putative metastatic driver mutations (LRP5 A65V and PEAK1), and 2) cells from this ancestral subclone acquired an ERBB2 activating mutation after their dissemination from the primary tumor, ostensibly as a mechanism of resistance to treatment. This evidence concerns the gene LRP5 and neoplasm.