Abstract P4-07-11: Prognostic significance of changes in tumor infiltrating lymphocytes and neutrophil-to-lymphocyte ratio after neoadjuvant chemotherapy in early breast cancer patients
Authors: Garcia-Torralba Esmeralda , Álvarez-Abril Beatriz , Bravo-Pérez Carlos , Manzano Esther Navarro , de la Morena Barrio Pilar , Rubio Alejandra Ivars , García-Garre Elisa , Zafra Gema Marín , de la Peña Francisco Ayala , García-Martínez Elena 
Published: March 2022

Abstract
Introduction. There are still 30-40% of patients with early breast cancer (BC) that relapse after neoadjuvant chemotherapy (NAC). New prognostic biomarkers are needed. Current evidence shows that both markers of antitumor local and systemic immune response, such as tumor infiltrating lymphocytes (TIL) and neutrophil-to-lymphocyte ratio (NLR) have prognostic value in early BC. Most works have evaluated baseline levels, but their variation after NAC might be related to treatment resistance and should be explored.The aim of this study was to simultaneously investigate the prognostic significance of the pre-post-NAC variation of TIL and NLR in patients with early BC.Methods. Retrospective, single-center cohort of 121 patients with early BC treated with NAC between 2001 and 2010. Pre- and post-NAC TIL (CD3+) were assessed by tumor tissue microarrays performed in both diagnostic core-needle biopsy and surgical excision specimens, respectively. Pre- and post-NAC NLR were calculated based on blood tests collected within 1 month of cancer diagnosis and at the moment of surgery, respectively. The change on TIL and NLR after NAC was estimated by calculating the absolute difference of post- and pre- values of these parameters (Δpost-pre). We examined the association between the absolute difference of TIL and NLR (both divided into deciles) and survival outcomes by Cox regression. To represent in Kaplan-Meier curves the combined effect of the change of TIL and NLR in OS, we divided patients into 4 groups, depending on the sign of Δpost-pre values of TIL and NLR: 1) no TIL nor NLR increment after NAC (ΔTIL & ΔNRLpost-pre≤0); 2) no TIL but NLR increment (ΔTILpost-pre≤0, ΔNRLpost-pre&gt;0); 3) TIL but no NLR increment (ΔTILpost-pre&gt;0, ΔNRLpost-pre≤0); and 4) TIL and NLR increment following NAC (ΔTIL & ΔNRLpost-pre&gt;0).Results. 47 (40%) out of 121 patients had pre- and post-NAC values of both NLR and TIL. Patients’ baseline characteristics are shown in Table 1. The median follow-up of this group was 11.5 years (IQR: 10.5 - 12.5 years). At the final follow-up date, overall survival (OS) was 87.2 %. In the univariable analysis, the increase in TIL and NLR after NAC among deciles showed a negative prognostic value for OS (TIL: HR 1.54, 95%CI 1.05-2.26, p=0.026; HR 1.32 95%CI 0.98-1.79, p=0.070). In the multivariable analysis, adjusted by cancer staging after NAC, both the increase of TIL and NLR after NAC among deciles add independent predictive value (TIL: HR 1.53, 95%CI 1.00-2.34, p=0.049; RNL: HR 1.42 95%CI 0.95-2.12, p=0.09).The subpopulation of patients with no TIL increment after NAC (Groups 1&2, N=23) showed the best prognosis, with no deaths at 10 years. Among patients with TIL increment (Groups 3&4, N=22), those with no NLR increment (Group 3, N=5) showed an intermediate prognosis (20% deaths at 10 years), whereas patients with concurrent NLR increment (Group 4, N=17) had the lowest OS (29.4% deaths at 10 years). Differences observed between groups were statistically significant (Log Rank p=0.042).Conclusion. The integrated characterization of TIL and NLR variations after NAC identifies different prognostic subgroups in early BC patients. In our cohort, both the increment of TIL and/or NLR after NAC are associated to a worse prognosis. Future validation of these findings in large, multicenter cohorts might allow treatment optimization by means of new strategies such as immunotherapy.
Table 1.Patients’ baseline characteristicsN=47Age (median, range)56 (21, 78)Menstrual statusPostmenopausal25 (53,2%)Premenopausal22 (46,8%)Histologic subtypeInvasive ductal carcinoma42 (91,5%)Other subtypes4 (8,5%)Histologic gradeGrade 12 (4,3%)Grade 218 (38,3%)Grade 323 (48,9%)Unknown4 (8,6%)cTcT221 (44,7%)cT324 (51,1%)cT4a-d2 (4,2%)cNcN018 (38,3%)cN114 (29,8%)cN26 (12,8%)cN39 (19,1%)Molecular subtypeHR+ HER2-22 (46,8%)HER2+ HR+8 (17,0%)HER2+ HR-6 (12,8%)Triple negative10 (21,3%)Breast surgeryConservative26 (55,3%)Mastectomy21 (44,7%)Axillary surgerySentinel lymph node biopsy12 (25,5%)Axillary lymph node dissection35 (74,5%)Relapse typeMetastasis7 (14,9%)Local/contralateral1 (0,83%)Deaths6 (12,8%)
Citation Format: Esmeralda Garcia-Torralba, Beatriz Álvarez-Abril, Carlos Bravo-Pérez, Esther Navarro Manzano, Pilar de la Morena Barrio, Alejandra Ivars Rubio, Elisa García-Garre, Gema Marín Zafra, Francisco Ayala de la Peña, Elena García-Martínez. Prognostic significance of changes in tumor infiltrating lymphocytes and neutrophil-to-lymphocyte ratio after neoadjuvant chemotherapy in early breast cancer patients [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-07-11.