Kashiwagi Shinichiro, Asano Yuka, Goto Wataru, Takada Koji, Takahashi Katsuyuki, Noda Satoru, Takashima Tsutomu, Onoda Naoyoshi, Tomita Shuhei, Ohsawa Masahiko, Hirakawa Kosei, Ohira Masaichi
Department of Surgical Oncology; Osaka City University Graduate School of Medicine, Osaka, Japan.
Department of Pharmacology, Osaka City University Graduate School of Medicine, Osaka, Japan.
PLoS One. 2017 Feb 6;12(2):e0170634. doi: 10.1371/journal.pone.0170634. eCollection 2017.
Eribulin mesylate (eribulin) is currently indicated for treatment of locally advanced or metastatic breast cancer (MBC). It is a cytotoxic agent with unique mechanisms that suppress epithelial-mesenchymal transition (EMT) of cancer cells. On the other hand, Tumor-infiltrating lymphocytes (TILs), which are considered indicators of immune response monitoring, have been reported as prognostic factors and predictors of therapeutic efficacy. We thought that eribulin, which has an EMT-inhibiting mechanism, may produce an antitumor effect by improving the immune microenvironment, and in this study investigated the effects of breast cancer eribulin chemotherapy on the immune microenvironment with TILs as a marker.
TILs was evaluated in 52 patients with MBC who underwent chemotherapy with eribulin. The correlation between TILs evaluated according to the standard method, and prognosis, including the efficacy of eribulin chemotherapy, was investigated retrospectively.
Of the 52 MBC patients, 29 (55.8%) were in the high TILs group and 23 (44.2%) were in the low TILs group. The high TILs group included significantly more triple-negative breast cancer (TNBC) (p = 0.008) than the low TILs group. In an analysis of outcomes, TNBC patients in the high TILs group had significantly longer disease-free survival than TNBC patients in the low TILs group (p = 0.033, log-rank), but no significant differences were seen in all breast cancer patients (p = 0.489, log-rank) or in non-TNBC patients (p = 0.878, log-rank). In a multivariate analysis of recurrence in TNBC patients, being in the high TILs group was again an independent factor for a good outcome (p = 0.031, HR = 0.063).
The results of this study suggest that TILs may be useful as a predictive marker of the therapeutic effect of eribulin chemotherapy in TNBC.
甲磺酸艾瑞布林（艾瑞布林）目前被用于治疗局部晚期或转移性乳腺癌（MBC）。它是一种具有独特机制的细胞毒性药物，可抑制癌细胞的上皮-间质转化（EMT）。另一方面，肿瘤浸润淋巴细胞（TILs）被认为是免疫反应监测的指标，已被报道为预后因素和治疗疗效的预测指标。我们认为，具有EMT抑制机制的艾瑞布林可能通过改善免疫微环境产生抗肿瘤作用，在本研究中，我们以TILs为标志物，研究了乳腺癌艾瑞布林化疗对免疫微环境的影响。
对52例接受艾瑞布林化疗的MBC患者的TILs进行评估。回顾性研究根据标准方法评估的TILs与预后（包括艾瑞布林化疗疗效）之间的相关性。
52例MBC患者中，29例（55.8%）为高TILs组，23例（44.2%）为低TILs组。高TILs组的三阴性乳腺癌（TNBC）患者明显多于低TILs组（p = 0.008）。在结果分析中，高TILs组的TNBC患者无病生存期明显长于低TILs组的TNBC患者（p = 0.033，对数秩检验），但在所有乳腺癌患者中未见显著差异（p = 0.489，对数秩检验），在非TNBC患者中也未见显著差异（p = 0.878，对数秩检验）。在TNBC患者复发的多因素分析中，处于高TILs组再次是预后良好的独立因素（p = 0.031，HR = 0.063）。
本研究结果表明，TILs可能作为TNBC中艾瑞布林化疗治疗效果的预测标志物。
