Interestingly, Y537 and D538 substitutions were identified in 7% of ER+ primary tumors using ddPCR, which may lead us to review the conclusion that ESR1 point mutations rarely exist in primary tumor, towards the idea that rare ESR1 mutant sub-clones exist in primary breast tumors that become selected for over time[60]. This evidence concerns the gene ESR1 and breast neoplasm.