Peripheral Blood Cell Ratios as Prognostic Indicators in a Neoadjuvant Chemotherapy-Treated Breast Cancer Cohort

Abstract

Breast cancer represents a heterogeneous condition in which the interaction between host immune response and primary oncogenic events can impact disease progression. Ratios of systemic blood-based immunocytes have emerged as clinically-relevant prognostic biomarkers in cancer patients. The NLR (neutrophil-to-lymphocyte ratio) has been shown to be prognostic in a variety of cancers, including breast cancer. However, evaluation of the prognostic value for overall survival (OS) and disease-free survival (DFS) of other key immunocyte ratios—neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), neutrophil-to-white cell count ratio (NWR), lymphocyte-to-white cell count ratio (LWR), monocyte-to-white cell count ratio (MWR), platelet-to-lymphocyte (PLR)—by breast cancer subtypes in a neoadjuvant chemotherapy (NAC) cohort remains to be fully explored. An NAC-treated breast cancer cohort, comprised of Luminal A, Luminal B, HER2-positive, and triple negative/basal breast cancers, treated at a tertiary referral center (minimum 3-year follow-up), was used to calculate immunocyte ratios and immunocyte cut-off values, calculated with >80% specificity (using decision tree modeling). The association with subtype-specific OS, DFS, and tumor grade was analyzed using cut offs calculated using both receiver operating characteristic curves and decision tree modelling. Decision tree calculated ratios showed that LMR (5.29) and MWR (0.06) were significantly associated with Luminal A OS (p = 0.004 and p = 0.022) and DFS (p = 0.004 and p = 0.022), and Luminal B OS (p = 0.027 and p = 0.008) and DFS (p = 0.005 and p = 0.007). NLR (1.79) and LWR (0.30) were significantly associated with HER2-positive OS (p = 0.013 and p = 0.043). NLR (1.79) and NWR (0.62) were significantly associated with DFS (p = 0.035 and p = 0.021). No significant association we observed between any immunocyte ratio in the triple negative cohort. Our results demonstrate the subtype-specific prognostic value of immunocyte ratios in NAC-treated breast cancer patients. Further validation of immunocyte ratios will provide clinicians with a new prognostic aid for disease management and monitoring.

A Mendelian randomization-based approach to explore the relationship between leukocyte counts and breast cancer risk in European ethnic groups

“…Therefore, in-depth studies targeting this area are beneficial to further reveal the pathogenesis of breast cancer and to improve its prevention and treatment measures. Peripheral blood leukocyte count is a routine clinical test, which is mainly used for the assessment of patients’ general condition and the diagnosis of acute bacterial infections, with the characteristics of being easy to perform and low cost 50 , 51 . As important immune cells in the organism, the levels of various leukocytes in peripheral blood can also reflect changes in immune function.…”

The prognostic value of absolute lymphocyte count and neutrophil‐to‐lymphocyte ratio for patients with metastatic breast cancer: a systematic review and meta‐analysis

“…Pretreatment neutrophil-to-lymphocyte ratio (NLR) and platelet-tolymphocyte ratio (PLR) and other immune and inflammatory biomarkers have been reported to be independent predictors of breast cancer prognosis (13)(14)(15). It was observed that these easy-toobtain, non-invasive, and individualized peripheral blood biomarkers are of great prognostic value in numerous tumors including breast cancer, and increased NLR and PLR and decreased ALC may be associated with poor prognosis (16,17). However, several previous meta-analyses only focus on breast cancer, and thus, there is still great uncertainty for the values of these potential prognostic biomarkers in MBC (2).…”