Peripheral blood lymphocytes predict clinical outcomes in hormone receptor-positive HER2-negative advanced breast cancer patients treated with CDK4/6 inhibitors Journal Article
| Authors: | Zattarin, E.; Mariani, L.; Menichetti, A.; Leporati, R.; Provenzano, L.; Ligorio, F.; Fucà, G.; Lobefaro, R.; Lalli, L.; Vingiani, A.; Nichetti, F.; Griguolo, G.; Sirico, M.; Bernocchi, O.; Marra, A.; Corti, C.; Zagami, P.; Agostinetto, E.; Jacobs, F.; Di Mauro, P.; Presti, D.; Sposetti, C.; Giorgi, C. A.; Guarneri, V.; Pedersini, R.; Losurdo, A.; Generali, D.; Curigliano, G.; Pruneri, G.; de Braud, F.; Dieci, M. V.; Vernieri, C. |
| Article Title: | Peripheral blood lymphocytes predict clinical outcomes in hormone receptor-positive HER2-negative advanced breast cancer patients treated with CDK4/6 inhibitors |
| Abstract: | 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. |
| Keywords: | adult; cancer survival; primary tumor; human cell; major clinical study; overall survival; cancer growth; monotherapy; bone metastasis; cancer patient; outcome assessment; follow up; prospective study; ki 67 antigen; cytology; progression free survival; thrombocyte; inflammation; cohort analysis; retrospective study; prediction; histology; liver metastasis; lung metastasis; proportional hazards model; neutrophil; multicenter study; brain metastasis; disease free interval; tumor immunity; blood cell; hormonal therapy; blood cell count; estrogen receptor; progesterone receptor; postmenopause; software; lymphocytes; skin metastasis; immunocompetent cell; lymphocyte count; fulvestrant; platelet count; endocrine therapy; peripheral lymphocyte; soft tissue metastasis; clinical outcome; first-line treatment; cancer prognosis; immunological parameters; advanced breast cancer; human; male; female; article; palbociclib; abemaciclib; random forest; neutrophil lymphocyte ratio; ribociclib; cdk4/6 inhibitors; ecog performance status; platelet lymphocyte ratio; human epidermal growth factor receptor 2 negative breast cancer; prognostic biomarkers; monocyte count; hormone receptor-positive, her2-negative breast cancer |
| Journal Title: | Therapeutic Advances in Medical Oncology |
| Volume: | 15 |
| ISSN: | 1758-8340 |
| Publisher: | Sage Publications Ltd. |
| Date Published: | 2023-01-01 |
| Start Page: | 17588359231204857 |
| Language: | English |
| DOI: | 10.1177/17588359231204857 |
| PROVIDER: | scopus |
| PMCID: | PMC10734364 |
| PUBMED: | 38130467 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
