Tumor-infiltrating lymphocytes predict prognosis of breast cancer patients treated with anti-Her-2 therapy
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Tan-Huan Chen1,2,*,**, Ying-Chun Zhang3,*, Yu-Ting Tan4,*, Xin An2,**, Cong Xue2,**, Ying-Fei Deng2,**, Wei Yang2,**, Xia Yuan1,**, Yan-Xia Shi2,**
1Department of Medical Oncology, Affiliated Hui Zhou Municipal Central Hospital & Training Base for Masters of Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Huicheng District, Huizhou, Guangdong 516000, P. R. China
2Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510000, P.R. China
3Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510000, P.R. China
4Department of Radiotherapy, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510000, P.R. China
*These authors have contributed equally to this work
**These corporations have contributed equally to this work
Yan-Xia Shi, email: [email protected]
Xia Yuan, email: [email protected]
Keywords: TILs, anti-Her-2 therapy, breast cancer, prognosis
Received: June 21, 2016 Accepted: November 21, 2016 Published: December 23, 2016
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.
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