Clémence Pinard1,2, Marc Debled3, Houda Ben Rejeb1, Valérie Velasco1, Christine Tunon de Lara4, Stéphanie Hoppe5, Elodie Richard6, Véronique Brouste5, Hervé Bonnefoi2,3,6, Gaëtan MacGrogan7,8. 1. Department of Biopathology, Institut Bergonié, Comprehensive Cancer Center, 229 Cours de l'Argonne CS61283-33076, 33000, Bordeaux, Cedex, France. 2. University of Bordeaux, 33000, Bordeaux, France. 3. Department of Medical Oncology, Institut Bergonié, 33000, Bordeaux, France. 4. Department of Surgery, Institut Bergonié, 33000, Bordeaux, France. 5. Department of Clinical Research and Medical Information, Institut Bergonié, 33000, Bordeaux, France. 6. INSERM U1218, 33000, Bordeaux, France. 7. Department of Biopathology, Institut Bergonié, Comprehensive Cancer Center, 229 Cours de l'Argonne CS61283-33076, 33000, Bordeaux, Cedex, France. G.MacGrogan@bordeaux.unicancer.fr. 8. INSERM U1218, 33000, Bordeaux, France. G.MacGrogan@bordeaux.unicancer.fr.
Abstract
PURPOSE: There is a need to refine the prognosis of triple-negative breast cancer (TNBC) patients after neoadjuvant chemotherapy (NAC) and to study the influence of the tumor microenvironment. We evaluated the prognostic value of pathological and immune markers in TNBC with residual disease (RD) after NAC. METHODS: In a series of 186 TNBC patients treated by NAC, we assessed the prognostic value of the Residual Cancer Burden (RCB) index. In 109 patients with RD, we studied the impact of clinicopathological features and tumor immune response in the residual tumor on overall survival (OS) and distant recurrence-free interval (DRFI). RESULTS: In the whole group, the OS and DRFI, at 3 years, were statistically different between the different classes of RCB (P = 0.0004 and P < 0.0001, respectively). In univariate analysis of the RD group, low RCB index and high ratios of stromal tumor-infiltrating lymphocytes (TILs), CD3 + TILs, CD4 + TILs, CD8 + TILs, and IDO1-positive cells were significant favorable prognostic factors for DRFI at 3 years. In the final multivariate model, CD4 + TILs and RCB index showed a statistically independent prognostic significance for DRFI [Hazard Ratio (HR) 2.88 (95%CI 1.34-6.17), P = 0.007 and HR 12.04 (95%CI 2.78-52.23, P < 0.0001), respectively]. The CD4 + TIL levels influenced survival in the different RCB classes with a significant effect observed in RCB-II and RCB-III classes (P = 0.05 and P = 0.05, respectively). CONCLUSIONS: These results suggest that the combination of pathological (RCB index) and tumor micro-environmental features (CD4 + TILs) help refining the prognosis of TNBC patients with RD following NAC.
PURPOSE: There is a need to refine the prognosis of triple-negative breast cancer (TNBC) patients after neoadjuvant chemotherapy (NAC) and to study the influence of the tumor microenvironment. We evaluated the prognostic value of pathological and immune markers in TNBC with residual disease (RD) after NAC. METHODS: In a series of 186 TNBC patients treated by NAC, we assessed the prognostic value of the Residual Cancer Burden (RCB) index. In 109 patients with RD, we studied the impact of clinicopathological features and tumor immune response in the residual tumor on overall survival (OS) and distant recurrence-free interval (DRFI). RESULTS: In the whole group, the OS and DRFI, at 3 years, were statistically different between the different classes of RCB (P = 0.0004 and P < 0.0001, respectively). In univariate analysis of the RD group, low RCB index and high ratios of stromal tumor-infiltrating lymphocytes (TILs), CD3 + TILs, CD4 + TILs, CD8 + TILs, and IDO1-positive cells were significant favorable prognostic factors for DRFI at 3 years. In the final multivariate model, CD4 + TILs and RCB index showed a statistically independent prognostic significance for DRFI [Hazard Ratio (HR) 2.88 (95%CI 1.34-6.17), P = 0.007 and HR 12.04 (95%CI 2.78-52.23, P < 0.0001), respectively]. The CD4 + TIL levels influenced survival in the different RCB classes with a significant effect observed in RCB-II and RCB-III classes (P = 0.05 and P = 0.05, respectively). CONCLUSIONS: These results suggest that the combination of pathological (RCB index) and tumor micro-environmental features (CD4 + TILs) help refining the prognosis of TNBC patients with RD following NAC.
Entities:
Keywords:
CD3; CD4; CD8; IDO1; Neoadjuvant chemotherapy; Prognosis of triple-negative breast cancer; RCB index; TILs; Tumor-infiltrating lymphocytes
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