Evaluation of Immune Reaction and PD-L1 Expression Using Multiplex Immunohistochemistry in HER2-Positive Breast Cancer: The Association With Response to Anti-HER2 Neoadjuvant Therapy

We examined PD-L1 expression together with immune markers in HER2(+) breast cancers and its association with the response to anti-HER2 therapy. Our results have demonstrated intratumoral CD8(+) lymphocytes were positively associated with pathologic complete response (pCR) in multivariate analysis, but PD-L1 was not. PD-L1's effect on pCR was probably dependant on coexistence of intratumoral CD8(+) lymphocytes. Our results suggest examination of intratumoral CD8(+) cells together with PD-L1 is useful in predicting response to anti-HER2 therapy in HER2(+) breast cancer patients. Background: Immune reaction with tumor-infiltrating lymphocytes (TILs) has been extensively investigated in breast cancer. Programmed cell death 1 and its ligand (PD-L1) are key physiologic suppressors of cytotoxic immune reaction. However, the combination of TILs with PD-L1 expression has not been well studied in breast cancer. Patients and Methods: A multi-color immunohistochemical multiplex assay simultaneously detecting PD-L1, CD8, and CD163 was performed on biopsy whole sections from 123 HER2-positive (HER2(+)) breast cancers, including 64 treated with anti-HER2 neoadjuvant therapy and subsequent resection. Results: PD-L1 expression was identified in 88 cases (72%) including 21 (17%) in tumor cells and 67 (55%) in immune cells. PD-L1 expression was positively associated with high Nottingham grade, high nuclear grade, and a high level of CD8(+) and CD163(+) cells. Among the 64 patients who received neoadjuvant therapy, 39 had pathologic complete remission (pCR) and 25 had incomplete response. Multivariate analysis showed progesterone receptor negativity, HER2/chromosome 17 centromere (CEN17) ratio and intratumoral CD8(+) cells were significantly associated with pCR. Furthermore, all patients with intratumoral CD8(+) cells but no PD-L1 expression achieved pCR. Conclusion: Our data have shown that examination of intratumoral CD8(+) cells together with PD-L1 expression proves useful in predicting response to anti-HER2 targeted therapy in patients with HER2(+) breast cancer. (C) 2017 Elsevier Inc. All rights reserved.