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RESEARCH PRODUCT

Association of derived neutrophil-to-lymphocyte ratio (dNLR) with pathological complete response (pCR) after neoadjuvant chemotherapy (CT)

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Abstract Background dNLR is a novel biomarker associated with clinical outcome in solid tumors including early stage breast cancer (BC). Here we report the association of dNLR with pCR in triple-negative (TN) and luminal BC patients (pts) treated with neoadjuvant CT. Methods This was a retrospective analysis of two randomized studies (GEICAM/2006-03 - NCT00432172 and ETNA - NCT01822314) involving 821 pts with early stage (>2cm) or locally advanced TN or luminal BC receiving anthracycline/taxane-based CT +/- carboplatin (GEICAM/2006-03) or nab-paclitaxel/paclitaxel followed by anthracycline regimen (ETNA). dNLR was calculated as the ratio of neutrophils and the difference between total leukocytes and neutrophils in peripheral blood before CT (baseline) and at the end of treatment (EOT). Logistic regression analyses were used to explore dNLR association with pCR at the two time points by molecular subtype. Results 684 and 137 pts were from ETNA and GEICAM/2006-03 study respectively (TN n = 308; Luminal n = 513). In TN subgroup median baseline dNLR was 1.61 [interquartile range (IQR): 1.25-2.04] and at EOT 1.65 (IQR: 0.96-2.22). In luminal BC median baseline dNLR was 1.68 (IQR: 1.22-1.96) and at EOT 1.48 (IQR: 0.86-1.93). No association with pCR was found in luminal BC. Baseline dNLR was associated with pCR in TNBC in univariate analysis (OR: 0.709, CI: 0.5-1.006, p = 0.0406). At EOT significant association of dNLR as continuous variable with pCR was observed in TNBC both in univariate and multivariate analysis (OR: 0.665, CI: 0.501-0.884, p = 0.0034, n = 255 and OR: 0.62, CI: 0.406-0.946, p = 0.0231, n = 228 respectively). Quartiles distribution of EOT dNLR was also associated with pCR in univariate and multivariate analysis (Q1 vs combined Q2/Q3/Q4 group: OR: 0.32, CI: 0.17-0.64, p = 5e-04 and OR: 0.26, CI: 0.1-0.63, p = 0.002 respectively). Also a ROC curve - based optimal cut off method revealed significant association of EOT dNLR with pCR in TNBC (>2.231, OR: 0.43, CI: 0.25-0.74, p = 0.0035). Conclusions No association was found between dNLR and pCR in luminal BC. High dNLR levels at baseline and especially EOT seem to be associated with worse clinical outcome in TN tumors after neoadjuvant CT. Clinical trial identification GEICAM/2006-03 - NCT00432172: 07 Feb 2007 ETNA - NCT01822314: 02 Abr 2013. Legal entity responsible for the study GEICAM Spanish Breast Cancer Group. Funding Has not received any funding. Disclosure M. Mansutti: Advisory / Consultancy: Celgene; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: AstraZeneca. A. Lluch: Research grant / Funding (self), Research grant / Funding (institution): Amgen; Research grant / Funding (self), Research grant / Funding (institution): AstraZeneca; Research grant / Funding (self), Research grant / Funding (institution): Boehringer-Ingelheim; Research grant / Funding (self), Research grant / Funding (institution): GSK; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Roche/Genentech; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Eisai; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Celgene; Research grant / Funding (self), Research grant / Funding (institution): Pierre-Fabre. M. Thill: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Genomic Health; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Celgene; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Eisai; Honoraria (self): Hexal; Honoraria (self), Travel / Accommodation / Expenses: Medtronic; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Myriad; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: PFM Medical; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: RTI Surgical; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Teva; Advisory / Consultancy, Travel / Accommodation / Expenses: Biom-up; Advisory / Consultancy, Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Travel / Accommodation / Expenses: Neodynamics; Advisory / Consultancy, Travel / Accommodation / Expenses: Norgine; Advisory / Consultancy, Travel / Accommodation / Expenses: Tesaro. L. Gianni: Advisory / Consultancy, MetIS, Novartis, Odonate Therapeutics, Revolution Medicine, Synaffix, Zymeworks: CONSULTANCY: ADC Therapeutics,; Advisory / Consultancy, RESEARCH FUNDING (institution): Zymeworks, Daiichi SankyoZymeworks, Daiichi Sankyo: AstraZeneca; Advisory / Consultancy, PATENTS, ROYALTIES: European Patent Application N. 12195182.6 and 12196177.5’, Roche: Celgene; Advisory / Consultancy: Lilly; Advisory / Consultancy: G1 Therapeutics; Advisory / Consultancy: Genentech; Advisory / Consultancy: Genomic Health; Advisory / Consultancy: MSD; Advisory / Consultancy: Oncolytics Biotech; Advisory / Consultancy: Odonate Therapeutics; Advisory / Consultancy: Onkaido; Advisory / Consultancy: Roche; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Tahio Pharmaceutical; Advisory / Consultancy: Sandoz; Advisory / Consultancy: SeaGen,; Advisory / Consultancy: Synthon; Advisory / Consultancy: Zymeworks,; Advisory / Consultancy: CD47; Advisory / Consultancy: GENENTA. All other authors have declared no conflicts of interest.