Role of ctDNA in Predicting the Outcome of Patients with Hormone Receptor–Positive, HER2-Negative Advanced Breast Cancer Treated with First-line Ribociclib and Letrozole: BioItaLEE Trial
Year: 2026
Type: article
Abstract: PURPOSE: This phase IIIb study prospectively evaluated the prognostic and predictive value of baseline and dynamic circulating tumor DNA (ctDNA) in postmenopausal patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) treated with first-line ribociclib/letrozole. EXPERIMENTAL DESIGN: A total of 287 patients were enrolled, with ctDNA analyzed at baseline (n = 263), day 15 of cycle 1 (C1D15; n = 238), C2D1 (n = 241), and first imaging (n = 206). The primary objective was to identify ctDNA alterations, characterize their evolution across treatment time points, and assess their association with progression-free survival (PFS). RESULTS: Median PFS was 23.4 months (95% confidence interval, 20.8 to not estimable). At baseline, the most frequently altered genes were PIK3CA (22.1%) and TP53 (15.5%). Alterations in TP53, MYC, and HER- and cyclin-dependent kinase 4/6- pathway genes were linked to early progression. Absence of a detectable mutation at baseline (n = 150, 57%) was associated with a better prognosis [hazard ratio (HR) = 0.41]. Among patients with a detectable mutation at baseline (n = 104), early clearance (mutation undetectability) was observed in 47.1% at C1D15 and 52.4% at C2D1 and was associated with improved PFS (C1D15, HR = 0.51; C2D1, HR = 0.44). In patients without a detectable mutation at baseline, 22.7% (n = 34) developed new mutations at C1D15, C2D1, or first imaging. Patients without new mutations had a lower risk of progression (HR = 0.45). CONCLUSIONS: Pretreatment and early dynamics of ctDNA represent promising prognostic and predictive biomarkers in patients with HR+/HER2- ABC treated with ribociclib/letrozole. Early ctDNA dynamics seem to be a promising surrogate biomarker for treatment. Further studies are warranted to validate their clinical utility.
Source: Clinical Cancer Research
Authors: Giampaolo Bianchini, Luca Malorni, Roberta Caputo, Alberto Zambelli, Fabio Puglisi, Giulia V. Bianchi, Lucia Del Mastro, Ida Paris, Filippo Montemurro, Marco Colleoni, Giacomo Allegrini, Stefano Tamberi, Claudio Zamagni, Marina E. Cazzaniga, Michele Orditura, Valentina Guarneri, Vincenzo Adamo, Emanuela Romagnoli, Maria Rosaria Valerio, Saverio Cinieri, Matteo Benelli, Maurizio Callari, Diletta Valsecchi, Daniela Castelletti, Donatella Grasso, Nicola Fenderico, Grazia Arpino, Michelino De Laurentiis
Institutions: IRCCS Ospedale San Raffaele, Azienda Usl Toscana Centro, Hospital of Prato, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale", Humanitas University, IRCCS Humanitas Research Hospital, University of Udine, Centro di Riferimento Oncologico, Fondazione IRCCS Istituto Nazionale dei Tumori, Ospedale Policlinico San Martino, University of Genoa, Agostino Gemelli University Polyclinic, Candiolo Cancer Institute, European Institute of Oncology, Ospedale di Livorno, University of Campania "Luigi Vanvitelli", Azienda Ospedaliera Universitaria Università degli Studi della Campania Luigi Vanvitelli, University of Padua, Istituto Oncologico Veneto, Azienda Ospedaliera Ospedali Riuniti Papardo Piemonte, Ospedale di Macerata, University of Palermo, Ospedale A. Perrino, Fondazione Michelangelo, Novartis (Italy), Federico II University Hospital, University of Naples Federico II
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W7125689672