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Prognostic Significance of Stromal Versus Intratumoral Infiltrating Lymphocytes in Different Subtypes of Breast Cancer Treated With Cytotoxic Neoadjuvant Chemotherapy

Khoury, Thaer, MD*; Nagrale, Vidya, MD*; Opyrchal, Mateusz, MD; Peng, Xuan, MS; Wang, Dan, PhD; Yao, Song, PhD§

Applied Immunohistochemistry & Molecular Morphology: September 2018 - Volume 26 - Issue 8 - p 523–532
doi: 10.1097/PAI.0000000000000466
Research Articles

Background: The aim of the study was to investigate if there were differences in associations of stromal versus intratumoral tumor infiltrating lymphocytes (TILs) with pathology complete response (pCR) among breast cancer (BC) subtypes treated with neoadjuvant therapy.

Materials and Methods: The hematoxylin and eosin slides of BC-core biopsy consecutive cases (n=331) were reviewed from a single institution between 2000 and 2014. TIL-stroma (TIL-str) was scored from 0% to 100%. Intratumoral lymphocytes (iTu-Ly) were scored semiquantitatively incorporating the infiltrate grade (0 to 3) and the corresponding percentage resulting in a score ranging from 0 to 300. pCR was defined as no residual infiltrating tumor in the tumor bed and the lymph nodes.

Results: pCR was achieved in 29 of 95 (30.9%) triple negative cases, 25 of 77 (32.5%) HER2+, and 9 of 159 (5.6%) luminal tumors. In univariate analysis, invasive nonlobular carcinoma, higher Nottingham grade, nonluminal subtypes, trastuzumab therapy, nonadvanced clinical T stage (T1 and T2), TIL-str, and iTu-Ly-predicted pCR. In luminal subtype, iTu-Ly but not TIL-str was an independent predictor for pCR [odds ratio (OR)=1.44, 95% confidence interval (CI), 1.08-1.9, P=0.013]. In triple negative subtype, both TIL-str and iTu-Ly were independent predictors for pCR (OR=1.68, 95% CI, 1.29-2.18, P=0.001; OR=1.31, 95% CI, 1.05-1.63, P=0.017, respectively). In HER2+ subtype, neither TIL-str nor iTu-Ly predicted pCR.

Conclusions: TILs are variably correlated with better neoadjuvant chemotherapy response depending on their location and clinical subtype of BC. It could indicate that TILs might be functionally heterogeneous with regard to their role in mediating antitumor immune response, depending on their location and BC subtypes.

Departments of *Pathology



§Epidemiology, Roswell Park Cancer Institute, Buffalo, NY

These data were presented in part as a platform in United States and Canadian Academy of Pathology in Seattle, WA, 2016.

The authors declare no conflict of interest.

Reprints: Thaer Khoury, MD, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, NY 14263 (e-mail:

Received July 12, 2016

Accepted September 28, 2016

Copyright 2018 Wolters Kluwer Health, Inc. All rights reserved.