Journal Article

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

Marra, Antonio, Dieci, Maria Vittoria, Vingiani, Andrea, Presti, Daniele, Losurdo, Agnese, Curigliano, Giuseppe, Griguolo, Gaia, Ligorio, Francesca, Nichetti, Federico, Giorgi, Carlo Alberto, Sirico, Marianna, Di Mauro, Pierluigi, Bernocchi, Ottavia, de Braud, Filippo, Guarneri, Valentina, Zagami, Paola, Generali, Daniele, Zattarin, Emma, Corti, Chiara, Fucà, Giovanni, Provenzano, Leonardo, Lalli, Luca, Mariani, Luigi, Agostinetto, Elisa, Lobefaro, Riccardo, Vernieri, Claudio, Leporati, Rita, Pedersini, Rebecca, Sposetti, Caterina, Pruneri, Giancarlo, Jacobs, Flavia, Menichetti, Alice

2023

Overview

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.

• Publisher: SAGE Publications,Sage Publications Ltd,SAGE Publishing
• Subject: Breast cancer / Clinical outcomes / Cyclin-dependent kinase 4 / Cyclin-dependent kinases / Endocrine therapy / ErbB-2 protein / Kinases / Leukocytes (neutrophilic) / Lymphocytes / Original Research / Patients / Peripheral blood