Peripheral blood lymphocytes predict clinical outcomes in hormone receptor-positive HER2-negative advanced breast cancer patients treated with CDK4/6 inhibitors.

Autor:	Zattarin E; Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Mariani L; Unit of Clinical Epidemiology and Trial Organization, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Menichetti A; Oncology 2, Istituto Oncologico Veneto IOV - IRCCS, Padova, Italy., Leporati R; Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Provenzano L; Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Ligorio F; Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.; IFOM ETS, the AIRC Institute of Molecular Oncology, Milan, Italy., Fucà G; Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Lobefaro R; Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Lalli L; Unit of Clinical Epidemiology and Trial Organization, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Vingiani A; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.; Pathology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Nichetti F; Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.; Computational Oncology, Molecular Diagnostics Program, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany., Griguolo G; Oncology 2, Istituto Oncologico Veneto IOV - IRCCS, Padova, Italy.; Department of Surgery, Oncology and Gastroenterology-DiSCOG, University of Padova, Padova, Italy., Sirico M; Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy., Bernocchi O; Farmacia Ospedaliera ASST Cremona, Cremona, Lombardia, Italy., Marra A; Division of Early Drug Development for Innovative Therapies, IEO, European Institute of Oncology IRCCS, Milan, Italy.; Breast Medicine Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Corti C; Division of Early Drug Development for Innovative Therapies, IEO, European Institute of Oncology IRCCS, Milan, Italy., Zagami P; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.; Division of Early Drug Development for Innovative Therapies, IEO, European Institute of Oncology IRCCS, Milan, Italy., Agostinetto E; IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.; Institut Jules Bordet and l'Université Libre de Bruxelles, Bruxelles, Belgium., Jacobs F; IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy., Di Mauro P; Medical Oncology Unit, ASST Spedali Civili, Brescia, Italy., Presti D; Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Sposetti C; Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Giorgi CA; Oncology 2, Istituto Oncologico Veneto IOV - IRCCS, Padova, Italy., Guarneri V; Oncology 2, Istituto Oncologico Veneto IOV - IRCCS, Padova, Italy.; Department of Surgery, Oncology and Gastroenterology-DiSCOG, University of Padova, Padova, Italy., Pedersini R; Medical Oncology Unit, ASST Spedali Civili, Brescia, Italy., Losurdo A; IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy., Generali D; Breast Cancer Unit & Translational Research Unit, ASST Cremona, Cremona, Italy.; Department of Medical, Surgery and Health Sciences, University of Trieste, Trieste, Italy., Curigliano G; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.; Division of Early Drug Development for Innovative Therapies, IEO, European Institute of Oncology IRCCS, Milan, Italy., Pruneri G; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.; Pathology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., de Braud F; Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy., Dieci MV; Oncology 2, Istituto Oncologico Veneto IOV - IRCCS, Padova, Italy.; Department of Surgery, Oncology and Gastroenterology-DiSCOG, University of Padova, Padova, Italy., Vernieri C; Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, Milan 20133, Italy IFOM ETS, the AIRC Institute of Molecular Oncology, Milan, Italy.
Jazyk:	angličtina
Zdroj:	Therapeutic advances in medical oncology [Ther Adv Med Oncol] 2023 Dec 20; Vol. 15, pp. 17588359231204857. Date of Electronic Publication: 2023 Dec 20 (Print Publication: 2023).
DOI:	10.1177/17588359231204857
Abstrakt:	Background: Cyclin-Dependent Kinase 4/6 inhibitors (CDK4/6i) combined with Endocrine Therapy (ET) are the standard treatment for patients with Hormone Receptor-positive/HER2-negative advanced breast cancer (HR+/HER2- aBC). Objectives: While CDK4/6i are known to reduce several peripheral blood cells, such as neutrophils, lymphocytes and platelets, the impact of these modulations on clinical outcomes is unknown. Design: A multicenter, retrospective-prospective Italian study. Methods: We investigated the association between baseline peripheral blood cells, or their early modifications (i.e. 2 weeks after treatment initiation), and the progression-free survival (PFS) of HR+/HER2- aBC patients treated with ETs plus CDK4/6i. Random Forest models were used to select covariates associated with patient PFS among a large list of patient- and tumor-related variables. Results: We evaluated 638 HR+/HER2- aBC patients treated with ET plus CDK4/6i at six Italian Institutions between January 2017 and May 2021. High baseline lymphocyte counts were independently associated with longer PFS [median PFS (mPFS) 20.1 versus 13.2 months in high versus low lymphocyte patients, respectively; adjusted Hazard Ratio (aHR): 0.78; 95% confidence interval (CI): 0.66-0.92; p = 0.0144]. Moreover, patients experiencing a lower early reduction of lymphocyte counts had significantly longer PFS when compared to patients undergoing higher lymphocyte decrease (mPFS 18.1 versus 14.5 months; aHR: 0.82; 95% CI: 0.73-0.93; p = 0.0037). Patients with high baseline lymphocytes and undergoing a lower reduction, or even an increase, of lymphocyte counts during CDK4/6i therapy experienced the longest PFS, while patients with lower baseline lymphocytes and undergoing a higher decrease of lymphocytes had the lowest PFS (mPFS 21.4 versus 11 months, respectively). Conclusion: Baseline and on-treatment modifications of peripheral blood lymphocytes have independent prognostic value in HR+/HER2- aBC patients. This study supports the implementation of clinical strategies to boost antitumor immunity in patients with HR+/HER2- aBC treated with ETs plus CDK4/6i. (© The Author(s), 2023.)
Databáze:	MEDLINE
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