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.
Integrating PIK3CA Testing into Clinical Practice for Advanced HR+/HER2- Breast Cancer: An Expert Consensus / De Angelis, Carmine; De Biase, Dario; Gerratana, Lorenzo; Arpino, Grazia; Bianchini, Giampaolo; Castellano, Isabella; Curigliano, Giuseppe; Del Mastro, Lucia; Fabi, Alessandra; Fusco, Nicola; Gennari, Alessandra; Guarneri, Valentina; Zamagni, Claudio; Zambelli, Alberto; Malapelle, Umberto; Puglisi, Fabio. - In: THE BREAST. - ISSN 0960-9776. - 87:(2026). [10.1016/j.breast.2026.104786]
Integrating PIK3CA Testing into Clinical Practice for Advanced HR+/HER2- Breast Cancer: An Expert Consensus
Arpino, Grazia;Malapelle, Umberto;
2026
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
