Distal inhibition with the mTORC1 inhibitor everolimus improved progression-free survival in combination with the aromatase inhibitor exemestane irrespective of the alteration status of the PI3K pathway, albeit at the cost of additional toxicity.3, 10 By contrast, proximal pathway inhibition with the PI3Kα-subunit specific inhibitor alpelisib significantly enhanced the efficacy of fulvestrant, but only in tumours harbouring PIK3CA hotspot mutations.11 This evidence concerns the gene PIK3CA and neoplasm.