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. 2017 Jan 17;8(3):5219-5232.
doi: 10.18632/oncotarget.14124.

Tumor-infiltrating lymphocytes predict prognosis of breast cancer patients treated with anti-Her-2 therapy

Tan-Huan Chen  1   2 , Ying-Chun Zhang  3 , Yu-Ting Tan  4 , Xin An  2 , Cong Xue  2 , Ying-Fei Deng  2 , Wei Yang  2 , Xia Yuan  1 , Yan-Xia Shi  2
Affiliations

Tumor-infiltrating lymphocytes predict prognosis of breast cancer patients treated with anti-Her-2 therapy

Tan-Huan Chen et al. Oncotarget. .

Abstract

Purpose: Infiltration of tumor associated lymphocytes and count of its different phenotypes are potentially new independent predictor of prognosis in breast cancer. However, research related to it is less reported in breast cancer patients treated with anti-Her-2 therapy. Thus, we evaluated the relationship between survival and tumor infiltrating lymphocytes including its different phenotypes in tumors of such patients.

Methods: Between 1999 and 2010, 98 patients diagnosed with primary breast cancer and treated with anti-Her-2 therapy at Sun-Yat-Sen University Cancer Center were included in the study. Biopsy specimens were collected post-operation but before chemotherapy. Tumor infiltrating lymphocytes as well as its FOXP3+, CD68+, IL-17+ phenotypes in both intratumoral and stromal sites and expression of FOXP3 in cancer cells were assessed.

Results: Median follow-up time of 98 patients was 83.3 months (range 7.4-201 months). It suggested that patients with high stromal infiltration of TILs, lower count of FOXP3+ Tregs and CD68+ Mφ in stromal site, and high expression of FOXP3 in cancer cells had longer survival of OS. In multivariate Cox regression analysis, high count of intratumoral CD68+ Mφ [HR: 2.70 (1.00-7.31); p=0.050] and high expression of FOXP3 in cancer cells [HR: 0.29 (0.09-0.91); p=0.034] were independent prognostic factors for overall survival.

Conclusions: Tumor infiltrating lymphocytes as well as its FOXP3+, CD68+ phenotypes in stromal site, and expression of FOXP3 in cancer cells were significantly associated with OS, suggesting that they can be used as important pathological factor predicting prognosis of breast cancer patients treated with anti-Her-2 therapy.

Keywords: TILs; anti-Her-2 therapy; breast cancer; prognosis.

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors declared that they have no competing interests.

Figures

Figure 1
Figure 1. Richness and absence of TILs in intratumoral and stromal sites by HE staining, 1×200
Figure 2
Figure 2. Infiltration of FOXP3+ Tregs, CD68+ Mφ, IL-17+ Th17 in intratumoral and stromal sites, and Foxp3 expression in cancer cells by IHC staining, 1×200
Figure 3
Figure 3. Kaplan-Meier curves of overall survival according to TILs infiltration in intratumoral and stromal sites and FOXP3 expression in cancer cells
Figure 4
Figure 4. Kaplan-Meier curves of overall survival according to infiltration of FOXP3+ Tregs, CD68+ Mφ, IL-17+ Th17 in intratumoral and stromal sites
See this image and copyright information in PMC

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