Combination of peripheral neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio is predictive of pathological complete response after neoadjuvant chemotherapy in breast cancer patients

Abstract

The immune system seems to play a fundamental role in breast cancer responsiveness to chemotherapy. We investigated two peripheral indicators of immunity/inflammation, i.e. neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR), in order to reveal a possible relationship with pathological complete response (pCR) in patients with early or locally advanced breast cancer treated with neoadjuvant chemotherapy (NACT).We retrospectively analyzed 373 consecutive patients affected by breast cancer and candidates to NACT. The complete blood cell count before starting NACT was evaluated to calculate NLR and PLR. ROC curve analysis determined threshold values of 2.42 and 104.47 as best cut-off values for NLR and PLR, respectively. The relationships between NLR/PLR and pCR, along with other clinical-pathological characteristics, were evaluated by Pearson's c 2 or Fisher's exact test as appropriate. Univariate and multivariate analyses were performed using a logistic regression model. NLR and PLR were not significantly associated with pCR if analyzed separately. However, when combining NLR and PLR, patients with a NLR low /PLR low profile achieved a significantly higher rate of pCR compared to those with NLR high and/or PLR high (OR 2.29, 95% CI 1.22e4.27, p 0.009). Importantly, the predictive value of NLR low /PLR low was independent from common prognostic factors such as grading, Ki67, and molecular subtypes.The combination of NLR and PLR may reflect patients' immunogenic phenotype. Low levels of both NLR and PLR may thus indicate a status of immune system activation that may predict pCR in breast cancer patients treated with NACT.

Neutrophil to Lymphocyte Ratio as Prognostic and Predictive Factor in Breast Cancer Patients: A Systematic Review

“…Graziano et al [27] showed that PCR rates were higher in patients with NLR low /PLR low than patients with NLR high /PLR high (OR = 1.98; 95%CI 1.01-3.89; p = 0.044).…”

“…Studies including All BC Molecular Subtypes: the PCR rate in the function of NLR was the primary objective in seven studies [22][23][24][25][27][28][29]. In all studies (except for two without definition), PCR was defined as the complete disappearance of invasive tumors in breast and lymph nodes (patients with residual ductal carcinoma in situ were also considered to have achieved PCR: ypT0/is pN0).…”

“…Among these studies, four [26][27][28][29] also evaluated the total lymphocyte count (n = 2) [26,28] or total neutrophil count before treatment (n = 2) [26,28], and other ratios, such as the lymphocyte to monocyte ratio (LMR) (n = 2) [26,29], neutrophil to monocyte ratio (NMR) (n = 2) [26,29] and PLR (n = 2) [27,29], as predictive and prognostic factors of survival. Lymphocyte count was not correlated with DFS and OS in the study by Marin Hernandez et al [26], whereas it was an independent predictive factor for PCR in the multivariate analysis in the work by Qian et al (OR = 4.37; 95%CI 1.43-13.39; p = 0.01) [28].…”

“…(1) Patients Receiving Neo-Adjuvant Therapy Ten studies reported data on NLR as a predictive or prognostic factor in patients receiving neo-adjuvant therapy [22][23][24][25][26][27][28][29][30][31]. Among these studies, eight included patients with all molecular subtypes [22][23][24][25][26][27][28][29], one included only patients with triple negative BC (TNBC) [31] and the last one included only patients with hormone receptor-positive/HER2-negative BC [30]. The NLR cut-off for the statistical analyses was between 1.7 and 3.33, and was computed by a receiver operating characteristic (ROC) curve analysis in all studies.…”

“…Five studies reported data on Asian populations [23,25,28,30,31]. In nine articles, the neo-adjuvant therapy protocols were described, and were based on anthracycline and/or taxane [23][24][25][26][27][28][29][30][31]. (Table 1).…”