The predictive value of neutrophil-to-lymphocyte ratio for overall survival and pathological complete response in breast cancer patients receiving neoadjuvant chemotherapy

Siming Gao; Wenjie Tang; Bingli Zuo; Lianne Mulvihill; Jinming Yu; Yishan Yu

doi:10.3389/fonc.2022.1065606

The predictive value of neutrophil-to-lymphocyte ratio for overall survival and pathological complete response in breast cancer patients receiving neoadjuvant chemotherapy

Front Oncol. 2023 Jan 16:12:1065606. doi: 10.3389/fonc.2022.1065606. eCollection 2022.

Authors

Siming Gao^{1

2}, Wenjie Tang¹, Bingli Zuo³, Lianne Mulvihill⁴, Jinming Yu¹, Yishan Yu¹

Affiliations

¹ Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
² Department of Oncology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
³ Department of Clinical Epidemiology and Biostatistics, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
⁴ Department of Radiation Oncology, Seidman Cancer Center, Case Western Reserve University School of Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH, United States.

Abstract

Purpose: Previous studies have reported that neutrophil-to-lymphocyte ratio (NLR) at pre-treatment was predictive for overall survival (OS) and pathologic complete response (pCR) in breast cancer (BC) patients receiving neoadjuvant chemotherapy (NAC). This study aims to explore the predictive role of both pre- and post-NLR for OS as well as longitudinal NLR kinetics towards pCR in BC patients undergoing NAC.

Methods: We retrospectively included 501 BC patients who received NAC from 2009 to 2018. NLR at pre-, mid (every two cycles of NAC)-, and post-treatment were collected. Overall, 421 patients were included in the survival analysis. These patients were randomly divided into a training cohort (n = 224) and a validation cohort (n = 197). A multivariable Cox model was built using all significant factors in the multivariable analysis from the training cohort. The performance of the model was verified in the validation cohort by the concordance index (C-index). Longitudinal analysis for pCR prediction of NLR was performed using a mixed-effects regression model among 176 patients who finished eight cycles of NAC.

Results: The median follow-up time was 43.2 months for 421 patients. In the training cohort, multivariable analysis revealed that ER status, clinical node stage, pCR, pre-NLR, and post-NLR (all p < 0.05) were independent predictors of OS. The OS nomogram was established based on these parameters. The C-indexes of the nomogram were 0.764 and 0.605 in the training and validation cohorts, respectively. In the longitudinal analysis, patients who failed to achieve pCR experienced an augment of NLR during NAC while NLR remained stable among patients with pCR. Pre-NLR tended to be significantly associated with OS in patients of HER2 overexpressing and TNBC subtypes (all p < 0.05), but not in Luminal A and Luminal B subtypes.

Conclusions: This study demonstrated the prognostic value of both pre-NLR and post-NLR on clinical outcomes in BC patients receiving NAC. A novel nomogram was established to predict OS. Non-pCR patients developed increased NLRs during NAC. Routine assessment of NLR may be a simple and affordable tool to predict prognosis for BC patients receiving NAC.

Keywords: breast cancer; neoadjuvant chemotherapy; neutrophil-to-lymphocyte ratio; nomogram; overall survival; pathologic complete response.

Grants and funding

The study was supported by funds from the National Key Research and Development Projects of China (2018YFC1312201), the Radiation Oncology Innovate Unit, Chinese Academy of Medical Sciences (2019RU071), and the Academic Promotion Program of Shandong First Medical University (2019ZL002).