Association Between Neutrophil-Lymphocyte Ratio and Oncotype Dx Recurrence Score in Early-Stage Hormonal Receptor-Positive, HER2-Negative, Node-Negative Breast Cancer

Abstract

Purpose

The correlation between the preoperative neutrophil-to-lymphocyte ratio (NLR) and Oncotype DX^® (ODX) recurrence score (RS) has not yet been established. We aimed to investigate the association between NLR and ODX RS in patients with hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2−) early-stage breast cancer (BC).

Patients and Methods

This retrospective study included consecutive patients with HR+/HER2−, node-negative primary BC who underwent surgical tumor resection from 2011 to 2019. Receiver operating characteristic curve analysis was used to obtain an optimal NLR cutoff value. Logistic regression analyses were used to estimate associations between various parameters and ODX RS. Furthermore, the factors significantly associated with the ODX RS in multivariable analysis were incorporated in a separate model and estimated using logistic regression.

Results

A total of 160 patients were enrolled. The optimal preoperative NLR cutoff was 2.15. Multivariable analysis revealed that NLR and tumor grade (G1/G2 vs G3) were independent predictive factors of high RS cutoff (≥26). Moreover, including the two variables yielded a stronger association; patients with low NLR and low-grade tumors were unlikely to have high RS (≥26; odds ratio [OR] = 0.03, 95% confidence interval [CI]: 0.006–0.154; p < 0.001). Conversely, the presence of any of the following factors made patients unlikely to have low RS (<16; OR = 0.34, 95% CI: 0.16–0.73; p = 0.006): high NLR, high grade, or high Ki-67 levels (>20).

Conclusion

NLR is a promising independent predictor of RS. Furthermore, in addition to tumor grade and Ki-67 level, they together are also a potential indicator of high and low RS. However, further studies are required to validate this hypothesis.

Keywords:

• neutrophil-to-lymphocyte ratio
• Oncotype Dx recurrence score
• early-stage breast cancer
• hormonal receptor-positive
• human epidermal growth factor receptor 2-negative
• node-negative breast cancer

Acknowledgments

The authors thank breast cancer coordinator Ms. Monera for her help with data collection.

Abbreviations

BC, Breast cancer; BMI, Body mass index; DFS, Disease-free survival; HR+, Hormone receptor-positive; HER2-, Human epidermal growth factor receptor 2-negative; IHC, Immunohistochemistry; ILC, Invasive lobular carcinoma; IQR, Interquartile range; LVI, Lymphovascular invasion; NLR, Neutrophil-to-lymphocyte ratio; ODX, Oncotype DX^®; OR, Odds ratio; OS, Overall survival; PLR, Platelet-to-lymphocyte ratio; RS, Recurrence score; ROC, Receiver operating characteristic.

Data Sharing Statement

All data generated or analyzed during this study are included in this published article.

Statement of Ethics

This study was approved by the Research Advisory Council of King Faisal Specialist Hospital & Research Centre (RAC number 2051-029, and conducted following the ethical principles of the Declaration of Helsinki (2000). The participants remained anonymous, and no identifying or protected health information was recorded.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas, took part in drafting, revising, or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

Dr. Taher Al-Tweigeri has received speaking honoraria from Roche, Novartis, and Lilly and has served as an advisory committee for these companies. The other authors declare no conflicts of interest.