Lymphocyte-Activation Gene-3 Expression and Prognostic Value in Neoadjuvant-Treated Triple-Negative Breast Cancer

Yunxuan Wang; Tieying Dong; Qijia Xuan; Hong Zhao; Ling Qin; Qingyuan Zhang

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자료유형: 학술저널

저자정보: Yunxuan Wang (Harbin Medical University Cancer Hospital) Tieying Dong (Harbin Medical University Cancer Hospital) Qijia Xuan (Harbin Medical University Cancer Hospital) Hong Zhao (Harbin Medical University Cancer Hospital) Ling Qin (Harbin Medical University Cancer Hospital) Qingyuan Zhang (Harbin Medical University Cancer Hospital China)

저널정보: 한국유방암학회 Journal of Breast Cancer Journal of Breast Cancer Vol.21 No.2

발행연도: 2018.1

수록면: 124 - 133 (10page)

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Purpose: In this study, we aimed to evaluate lymphocyte-activation gene-3 (LAG-3) expression and its prognostic value in neoadjuvant- treated triple-negative breast cancer (TNBC). Methods: LAG-3, programmed death-1 (PD-1), programmed death ligand- 1 (PD-L1), and CD8+ tumor-infiltrating lymphocyte (TILs) levels were examined using immunohistochemistry in 148 preand 114 post-neoadjuvant chemotherapy (NACT) specimens of human TNBC tissue. Correlations between expression levels and clinicopathological features were analyzed. Prognostic values for combined detection in TNBC following NACT were evaluated. Results: In pre-NACT specimens, LAG-3 expression showed a significant association with pathological complete response (pCR, p=0.038) and was correlated with PD-1 (p<0.001) and PD-L1 (p=0.008). In post-NACT specimens, high expression of LAG-3 showed significant effects on nodal status (p=0.023) and PD-1 (p<0.001). The expression of immune markers on TILs significantly increased following NACT. Multivariate analysis indicated that only nodal status (odds ratio [OR], 0.226; 95% confidence interval [CI], 0.079–0.644; p=0.005) and high quantities of CD8+TILs (OR, 3.186; 95% CI, 1.314–7.721; p=0.010) are independent predictors of pCR. Nodal status (hazard ratio [HR], 2.666; 95% CI, 1.271–5.594; p=0.010), CD8+TILs (HR, 0.313; 95% CI, 0.139–0.705; p=0.005), and the LAG-3- high/PD-L1-high group (HR, 2.829; 95% CI, 1.050–7.623; p=0.040) provided prognostic values for patients with TNBC following NACT. Conclusion: CD8+TILs were sensitive predictive markers in response to NACT. High expression of LAG-3 in residual tissues, especially in combination with PD-L1, was associated with poor prognosis.

참고문헌 (30)

참고문헌 신청

Rakha EA / 2007 / Prognostic markers in triple-negative breast cancer / Cancer 109:25~32

Caudle AS / 2012 / Local-regional control according to surrogate markers of breast cancer subtypes and response to neoadjuvant chemotherapy in breast cancer patients undergoing breast conserving therapy / Breast Cancer Res 14:R83

Adams S / 2014 / Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trials: ECOG 2197 and ECOG 1199 / J Clin Oncol 32:2959~2966

Denkert C / 2015 / Tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy with or without carboplatin in human epidermal growth factor receptor 2-positive and triple-negative primary breast cancers / J Clin Oncol 33:983~991

Dushyanthen S / 2015 / Relevance of tumor-infiltrating lymphocytes in breast cancer / BMC Med 13:202

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