Carmine De Angelis, Dario de Biase, Lorenzo Gerratana, G. Arpino, Giampaolo Bianchini, Isabella Castellano, Giuseppe Curigliano, Lucia Del Mastro, Alessandra Fabi, N. Fusco, Alessandra Gennari, Valentina Guarneri, Claudio Zamagni, A. Zambelli, Umberto Malapelle, Fabio Puglisi
BACKGROUND: Alterations in the PI3K/AKT/mTOR signaling pathway represent a mechanism of resistance to endocrine therapy in advanced HR+/HER2-breast cancer. The identification of activating mutations in PIK3CA has gained therapeutic relevance, guiding the use of PIK3CA-targeted inhibitors such as alpelisib and inavolisib. METHODS: A multidisciplinary panel of Italian experts conducted a structured consensus process to develop shared recommendations for molecular testing of PIK3CA in advanced HR+/HER2-breast cancer, addressing preanalytical, analytical, and clinical-therapeutic areas of concern. RESULTS: A total of 23 out of 29 statements reached complete agreement (100%). The resulting recommendations encompass sample selection, analytical methodologies, sensitivity thresholds, result reporting, and clinical interpretation and integration. Additional guidance is provided for the management of non-canonical gene variants and for other genes involved in the PI3K/AKT/mTOR pathway. CONCLUSIONS: This consensus document provides operational and interpretative guidelines aimed at standardizing PIK3CAtesting and assessing related genes in clinical practice. These recommendations promote a harmonized approach to patient care, in line with the latest scientific evidence.