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

CDK4/6 inhibitors advanced breast cancer endocrine therapy lymphocytes prognostic biomarkers

Journal

Therapeutic advances in medical oncology
ISSN: 1758-8340
Titre abrégé: Ther Adv Med Oncol
Pays: England
ID NLM: 101510808

Informations de publication

Date de publication:
2023
Historique:
received: 10 04 2023
accepted: 14 09 2023
medline: 22 12 2023
pubmed: 22 12 2023
entrez: 22 12 2023
Statut: epublish

Résumé

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). 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. A multicenter, retrospective-prospective Italian study. 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. 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 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.

Sections du résumé

Background UNASSIGNED
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 UNASSIGNED
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 UNASSIGNED
A multicenter, retrospective-prospective Italian study.
Methods UNASSIGNED
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 UNASSIGNED
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
Conclusion UNASSIGNED
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.

Identifiants

pubmed: 38130467
doi: 10.1177/17588359231204857
pii: 10.1177_17588359231204857
pmc: PMC10734364
doi:

Types de publication

Journal Article

Langues

eng

Pagination

17588359231204857

Informations de copyright

© The Author(s), 2023.

Auteurs

Emma Zattarin (E)

Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Luigi Mariani (L)

Unit of Clinical Epidemiology and Trial Organization, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Alice Menichetti (A)

Oncology 2, Istituto Oncologico Veneto IOV - IRCCS, Padova, Italy.

Rita Leporati (R)

Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Leonardo Provenzano (L)

Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Francesca Ligorio (F)

Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
IFOM ETS, the AIRC Institute of Molecular Oncology, Milan, Italy.

Giovanni Fucà (G)

Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Riccardo Lobefaro (R)

Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Luca Lalli (L)

Unit of Clinical Epidemiology and Trial Organization, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Andrea Vingiani (A)

Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
Pathology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Federico 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.

Gaia Griguolo (G)

Oncology 2, Istituto Oncologico Veneto IOV - IRCCS, Padova, Italy.
Department of Surgery, Oncology and Gastroenterology-DiSCOG, University of Padova, Padova, Italy.

Marianna Sirico (M)

Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.

Ottavia Bernocchi (O)

Farmacia Ospedaliera ASST Cremona, Cremona, Lombardia, Italy.

Antonio 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.

Chiara Corti (C)

Division of Early Drug Development for Innovative Therapies, IEO, European Institute of Oncology IRCCS, Milan, Italy.

Paola 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.

Elisa 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.

Flavia Jacobs (F)

IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.

Pierluigi Di Mauro (P)

Medical Oncology Unit, ASST Spedali Civili, Brescia, Italy.

Daniele Presti (D)

Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Caterina Sposetti (C)

Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Carlo Alberto Giorgi (CA)

Oncology 2, Istituto Oncologico Veneto IOV - IRCCS, Padova, Italy.

Valentina Guarneri (V)

Oncology 2, Istituto Oncologico Veneto IOV - IRCCS, Padova, Italy.
Department of Surgery, Oncology and Gastroenterology-DiSCOG, University of Padova, Padova, Italy.

Rebecca Pedersini (R)

Medical Oncology Unit, ASST Spedali Civili, Brescia, Italy.

Agnese Losurdo (A)

IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.

Daniele Generali (D)

Breast Cancer Unit & Translational Research Unit, ASST Cremona, Cremona, Italy.
Department of Medical, Surgery and Health Sciences, University of Trieste, Trieste, Italy.

Giuseppe 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.

Giancarlo Pruneri (G)

Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
Pathology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Filippo 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.

Maria Vittoria Dieci (MV)

Oncology 2, Istituto Oncologico Veneto IOV - IRCCS, Padova, Italy.
Department of Surgery, Oncology and Gastroenterology-DiSCOG, University of Padova, Padova, Italy.

Claudio 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.

Classifications MeSH