Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Khoury T

PROVIDER: S-EPMC5550367 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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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 T Nagrale Vidya V Opyrchal Mateusz M Peng Xuan X Wang Dan D Yao Song S

Applied immunohistochemistry & molecular morphology : AIMM 20180901 8

<h4>Background</h4>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.<h4>Materials and methods</h4>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%. Intra ...[more]

PMID: 28187033

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Project description:The immunobiology of breast cancer (BC) subtypes, including luminal cancer, remains unclear. Cluster of differentiation (CD)8+ tumor-infiltrating lymphocytes (TIL) are essential components of tumor-specific cellular adaptive immunity. However, only few studies have addressed the significance of cluster of differentiation 8+(CD8+) TIL in patients with luminal BC. The present study aimed to evaluate the predictive and prognostic significance of CD8+ TIL in patients with luminal B/human epidermal growth factor receptor 2 (HER 2)-negative BC treated with anthracycline-based neoadjuvant chemotherapy (NC). A total of 31 patients who underwent breast-conserving surgery or mastectomy post-NC were enrolled. Immunostaining for CD8+ TIL was performed using rabbit monoclonal antibodies against human CD8+. Intra- and peritumoral CD8+ TIL expression levels were classified into high and low, based on the median value of each. CD8+ TIL expression data were demonstrated to be correlated with disease-free survival (DFS) and overall survival (OS), using Kaplan-Meier and Cox's proportional hazards regression tests. The results revealed that, among all clinicopathological characteristics, only pathological complete response (pCR) was significantly correlated with intratumoral CD8+ TIL expression (P=0.016). A total of 9/16 patients (56%) with high intratumoral CD8+ TIL expression achieved pCR, in contrast with 2 out of 15 patients (13.3%) with low expression (P=0.016). High expression of intratumoral CD8+ TIL was significantly associated with OS (log-rank test, P=0.023). Multivariate Cox regression analysis revealed that intratumoral expression of CD8+ TIL was an independent prognostic factor for OS [hazard ratio (HR)=2.82; 95% confidence interval (CI)=0.911-4.833, P=0.007], but not for DFS (HR=1.11; 95% CI=0.282-2.078; P=0.508). In conclusion, the results of the present study suggested that high intratumoral CD8+ TIL expression was significantly predictive of pCR post-NC, and represented an independent prognostic factor for improved OS. In contrast, low intratumoral CD8+ TIL expression was a strong predictor of lack of pCR to NC, as well as an independent prognostic factor for poor OS. Assessment of the immune response in conjunction with the usual parameters may aid in the further stratification of patients with luminal B/HER 2-negative BC regarding the prediction of pCR post-NC and overall prognosis.

Dataset Information

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

Publications

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

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