Shiwei Liu1, Shiyan Zeng1, Li Xia1, Miao Yu1, Xin Zhang1, Hong Yang2, Juan Ji2, Hao Dong2, Jianhui Zhang1, Purong Zhang3. 1. Department of Breast Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610000, China. 2. Department of Pathology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610000, China. 3. Department of Breast Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610000, China. PurongZhang@outlook.com.
Abstract
PURPOSE: The present study evaluated tumor-infiltrating lymphocytes (TILs) based on standardized scoring method and investigated its predictive value for axillary pathologic complete response (apCR) and prognostic significance for event-free survival (EFS) in neoadjuvant-treated HER2-positive breast cancer with initially biopsy-proven nodal metastasis. METHODS: We assessed TILs in a total of 187 pretherapeutic core biopsies of primary tumors. Receiver operating characteristic curve analysis was conducted to calculate the optimal cut-off point of TILs in discriminating axillary pathologic response. The associations of TILs with apCR or EFS were investigated by univariate and multivariate analyses. RESULTS: Receiver operating characteristic curve analysis identified a 10% cut-off point of TILs that optimally discriminated apCR from non-apCR (P < 0.001). High TILs were determined as TILs ≥ 10%, and tumor with TILs < 10% was defined as lymphocyte-depleted breast cancer (LDBC). The apCR rate of the entire cohort was 66.3% (124/187). Tumors with high TILs had a significantly higher apCR rate compared with LDBC (78.5% vs. 43.9%; P < 0.001). High TILs (P < 0.001), breast pathologic complete response (P = 0.006), and negative status of hormone receptor (P = 0.021) were independent predictors for apCR. High TILs were a markedly powerful predictor with an odds ratio of 4.01 (P < 0.001). EFS was significantly better among patients with high TILs than among those with LDBC (P < 0.001). Univariate and multivariate analyses indicated that high TILs (P = 0.019) and apCR (P = 0.013) were independent predictors for favorable EFS. CONCLUSIONS: TILs have predictive value for apCR and prognostic significance for EFS in initially node-positive and HER2-positive breast cancer treated with neoadjuvant therapy. LDBC (TILs < 10%) has a significantly unfavorable impact on apCR rate and EFS.
PURPOSE: The present study evaluated tumor-infiltrating lymphocytes (TILs) based on standardized scoring method and investigated its predictive value for axillary pathologic complete response (apCR) and prognostic significance for event-free survival (EFS) in neoadjuvant-treated HER2-positive breast cancer with initially biopsy-proven nodal metastasis. METHODS: We assessed TILs in a total of 187 pretherapeutic core biopsies of primary tumors. Receiver operating characteristic curve analysis was conducted to calculate the optimal cut-off point of TILs in discriminating axillary pathologic response. The associations of TILs with apCR or EFS were investigated by univariate and multivariate analyses. RESULTS: Receiver operating characteristic curve analysis identified a 10% cut-off point of TILs that optimally discriminated apCR from non-apCR (P < 0.001). High TILs were determined as TILs ≥ 10%, and tumor with TILs < 10% was defined as lymphocyte-depleted breast cancer (LDBC). The apCR rate of the entire cohort was 66.3% (124/187). Tumors with high TILs had a significantly higher apCR rate compared with LDBC (78.5% vs. 43.9%; P < 0.001). High TILs (P < 0.001), breast pathologic complete response (P = 0.006), and negative status of hormone receptor (P = 0.021) were independent predictors for apCR. High TILs were a markedly powerful predictor with an odds ratio of 4.01 (P < 0.001). EFS was significantly better among patients with high TILs than among those with LDBC (P < 0.001). Univariate and multivariate analyses indicated that high TILs (P = 0.019) and apCR (P = 0.013) were independent predictors for favorable EFS. CONCLUSIONS: TILs have predictive value for apCR and prognostic significance for EFS in initially node-positive and HER2-positive breast cancer treated with neoadjuvant therapy. LDBC (TILs < 10%) has a significantly unfavorable impact on apCR rate and EFS.
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