Department of General Surgical Science, Gunma University Graduate School of Medicine, Gunma, Japan.
Division of Breast Surgery, Saitama Cancer Center, Saitama, Japan.
Sci Rep. 2019 Nov 13;9(1):16662. doi: 10.1038/s41598-019-52944-6.
Several ongoing clinical trials are investigating the use of immuno-targeting therapy with programmed cell death protein-1 and programmed death-ligand 1 (PD-L1) inhibitors for triple-negative breast cancer. However, the role of PD-L1 expression in HER2-positive breast cancer remains unclear. We investigated the clinicopathological utility of PD-L1 expression in HER2-positive breast cancer. Cohort A included 248 patients with invasive breast cancer (all subtypes). Cohort B included 126 HER2-positive patients who received neoadjuvant chemotherapy (NAC) concomitant with trastuzumab. The relationship of PD-L1 expression on the cancer cells with clinicopathological factors including pathological complete response (pCR) and prognosis was investigated. In cohort A, 8.1% patients were PD-L1-positive; PD-L1 positivity showed a correlation with high degree of tumor-infiltrating lymphocytes (TILs), estrogen receptor negativity, progesterone receptor negativity, and high histological grade. In cohort B, 17.5% patients were PD-L1-positive; PD-L1 positivity showed a significant correlation with high degree of TILs and high abundance of CD8-positive TILs. The pCR rates were related to TILs and PD-L1 expression. Among PD-L1-negative patients, high CD8-positive TILs were associated with significantly better prognosis. In conclusion, 17.5% of HER2-positive type patients were PD-L1-positive. PD-L1 expression was associated with response to NAC with trastuzumab in patients with HER2-positive breast cancer.
几项正在进行的临床试验正在研究免疫靶向治疗,使用程序性细胞死亡蛋白-1 和程序性死亡配体 1(PD-L1)抑制剂治疗三阴性乳腺癌。然而,PD-L1 表达在 HER2 阳性乳腺癌中的作用仍不清楚。我们研究了 PD-L1 表达在 HER2 阳性乳腺癌中的临床病理效用。队列 A 包括 248 例浸润性乳腺癌(所有亚型)患者。队列 B 包括 126 例接受新辅助化疗(NAC)联合曲妥珠单抗治疗的 HER2 阳性患者。研究了 PD-L1 表达在癌细胞上与临床病理因素(包括病理完全缓解(pCR)和预后)的关系。在队列 A 中,8.1%的患者为 PD-L1 阳性;PD-L1 阳性与高肿瘤浸润淋巴细胞(TILs)、雌激素受体阴性、孕激素受体阴性和高组织学分级有关。在队列 B 中,17.5%的患者为 PD-L1 阳性;PD-L1 阳性与高 TILs 和高 CD8+TILs 丰度显著相关。pCR 率与 TILs 和 PD-L1 表达有关。在 PD-L1 阴性患者中,高 CD8+TILs 与显著更好的预后相关。总之,17.5%的 HER2 阳性型患者为 PD-L1 阳性。PD-L1 表达与接受 NAC 联合曲妥珠单抗治疗 HER2 阳性乳腺癌患者的反应相关。