Roberta Scafetta, Raffaella Troiano, Alessandra Guarino, Carla Gullotta, Cristina Fiore, Luisana Sisca, Elena Speziale, Arianna Travisani, Fernando Zannino, Giovanni Miraglia, Marco Donato, Simone Foderaro, Fabio Venuti, Francesco Antonio Vilardi, Valentina Ricozzi, Michele Iuliani, Sonia Simonetti, Silvia Cavaliere, Alessio Cortellini, Annalisa La Cesa, Andrea Di Mattia, Michela Lombardo, Martina Angelone, Andrea Botticelli, Simone Scagnoli, Simona Pisegna, Carmen Criscitiello, Rebecca Pedersini, Caterina Sposetti, Elisa Tiberi, Giuliana D'Auria, Matteo Vergati, Marco Mazzotta, Roberta Caputo, Annarita Verrazzo, Maria Grazia Rossino, Ornella Garrone, Federica Domati, Claudia Piombino, Federica Gatti, Lorena Filomeno, Teresa Arcuri, Federica Puce, Federica Riva, Michela Palleschi, Marianna Sirico, Marta Piras, Luigia Stefania Stucci, Delia De Lisi, Paolo Orsaria, Antonella Grasso, Edy Ippolito, Sara Ramella, Luca Visani, Lorenzo Livi, Stefania Gori, Luigi Rossi, Icro Meattini, Barbara Tagliaferri, Orazio Caffo, Ilaria Portarena, Azzurra Irelli, Elisabetta Cretella, Camillo Porta, Giampaolo Bianchini, Maria Agnese Fabbri, Ugo De Giorgi, Patrizia Vici, Angela Toss, Fiorella Ruatta, Michelino De Laurentiis, Federica Villa, Rossana Berardi, Mauro Minelli, Vittorio Altomare, Claudio Vernieri, Giuseppe Curigliano, Alessandra Chirco, Sara D'Alessandro, Bruno Vincenzi, Giuseppe Tonini, Daniele Santini, Francesco Pantano
Broad baseline-variable profiling identified PR expression as the most reproducible tumour-biological correlate of visceral conversion, although its stand-alone predictive performance was modest.
BACKGROUND: Bone-only HR+/HER2 - metastatic breast cancer generally has a favourable prognosis, but some patients develop visceral metastases. We aimed to quantify visceral conversion and identify reproducible baseline correlates during CDK4/6 inhibitor (CDK4/6i) therapy.
METHODS: This multicentre retrospective cohort included 692 patients treated with palbociclib, ribociclib, or abemaciclib plus endocrine therapy as first- or second-line treatment across 24 Italian centres. Visceral conversion was analysed in a competing-risks framework, with skeletal progression or death without prior visceral conversion as competing events. Eighteen baseline candidate predictors derived from a 35-variable dataset were evaluated using Fine-Gray modelling, ridge penalisation, bootstrap stability assessment, and cause-specific Cox sensitivity analyses.
RESULTS: Over a median follow-up of 31 months, 162 patients (23.4%) developed visceral conversion after a median of 17.0 months. Cumulative incidence was 8.8%, 17.5%, and 24.5% at 12, 24, and 36 months, respectively; median overall survival after visceral conversion was 18.0 months. Progesterone receptor (PR) expression was the most stable tumour-biological correlate, with complete sign concordance and a median absolute coefficient rank of 1 across 500 bootstrap resamples. In the mutually adjusted Fine-Gray model, higher PR expression was associated with lower visceral-conversion risk (sHR per 10-percentage-point increase, 0.929; 95% CI, 0.889-0.971; p = 0.0012), with consistent direction across complementary analyses. However, stand-alone PR prediction remained modest (24-month IPCW AUC, 0.585; Brier score, 0.142; IPA, 1.1%; O:E, 1.00), limiting individual-level clinical utility.
CONCLUSIONS: Broad baseline-variable profiling identified PR expression as the most reproducible tumour-biological correlate of visceral conversion, although its stand-alone predictive performance was modest.