Breast and Endocrine Surgery, Gunma University Hospital and Division of Breast Surgery, Saitama Cancer Center, Gunma, Japan
Sasagu Kurozumi , Kenichi Inoue , Masafumi Kurosumi , Hiroshi Matsumoto , Yuji Hayashi , Katsunori Tozuka , Kazuyuki Kubo , Kei Komatsu , Ken Takai , Shigenori E. Nagai , Hanako Oba , Jun Horiguchi
Background: The predictive and prognostic values of tumor-infiltrating lymphocytes(TILs) in neoadjuvant chemotherapy have also been demonstrated in triple negative as well as HER2-positive breast cancer (BC). In the present study, we investigated the relationship between the expression and degree of stromal (str)-TILs, CD8+ TILs, and PDL-1 positive cancer cells, and evaluated the values of these 3 factors for predicting pCR and prognosis in HER2-positive BC patients receiving neoadjuvant chemotherapy with trastuzumab. Methods: A total of 128 Japanese HER2-positive BC received taxanes followed by FEC, with the concomitant administration of trastuzumab. The grades of str-TILs were evaluated using the criteria of the International Working Group for TILs in BC, with a high grade being defined as > 40%. Immunohistochemically, positive cancer cells for PDL-1 was defined as > 1%, and high CD8+ was defined as the number of CD8+ TILs > 25 / 1 high power field. The relationship between the expression and degree of str-TILs, CD8+ TILs, and PDL-1 was investigated, as was that with pCR. In addition, the relationships of relapse-free survival (RFS) and overall survival (OS) with str-TILs, CD8+ TILs, and PDL-1 were examined. Results: pCR was achieved in 83 patients (pCR rate, 64.8%) who received NAC with trastuzumab, and RFS was significantly better in the pCR group than in the non-pCR group (p = 0.0071). A high degree of str-TILs correlated with high CD8+ (p = 0.0022) and positive PD-L1 (p < 0.0001). pCR rates correlated with the grades of str-TILs (high, 83.3% vs. low, 60.6%; p = 0.035) and PD-L1 expression (positive, 86.4% vs. negative, 61.5%; p = 0.026), but not with the density of CD8+ TILs (high, 70.1% vs. low, 56.6%; p = 0.18). In PD-L1-negative patients, survival was significantly better in the high CD8+ group than in the low CD8+ group (RFS: p = 0.0013; OS: p = 0.015). Conclusions: High-grade str-TILs and positive PD-L1 were identified as predictive factors of pCR in patients receiving NAC with trastuzumab, and high CD8+ TILs was a predictive factor of better survival in PDL1-negative and HER2-positive BC.
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