PIK3CA and neoplasm: Identification of these PIK3CA mutations are informative about treatment with the PI3Kα-specific inhibitor alpelisib in combination with fulvestrant as second-line therapy for advanced disease [114, 115] and, accordingly, the NCCN guidelines for invasive breast cancer (version 1.2022) (https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1419) recommend assessment for PIK3CA mutations using tumor tissue or ctDNA testing, with reflex tumor testing if ctDNA results are negative.