Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
Department of Public Health, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
BMC Cancer. 2017 Aug 31;17(1):604. doi: 10.1186/s12885-017-3598-5.
The recently developed reagent, eribulin mesylate (eribulin), is a microtubule dynamics inhibitor with a mechanism of action that differs from those of taxanes and vinca alkaloids. This drug is considered to be a promising chemotherapeutic agent for the treatment of locally advanced or metastatic breast cancer (MBC). In this study, we investigated if variables such as tumor expression of β-tubulin class III, glutathione S-transferase pi (GSTP) 1 or transducin-like enhancer of split (TLE) 3 might act as predictive factors on the therapeutic effect of eribulin chemotherapy.
The subjects included 52 patients with MBC who underwent chemotherapy with eribulin. The expression levels of Estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor (HER) 2, Ki67, β-tubulin class III, GSTP-1 and TLE-3 were evaluated using immunostaining employing needle biopsy specimens.
Patients with TLE3-negative tumors displayed significantly poorer outcomes regarding progression-free survival than patients with TLE3-positive tumors when prognosis within the group of patients with triple-negative breast cancer (TNBC) lesions was analyzed (p = 0.011, log-rank). In contrast, no such difference in prognosis was found in a comparison of TLE-3 positive/negative patients in the group of all patients (p = 0.433, log-rank) or of patients with non-TNBC lesions (p = 0.659, log-rank). Based on a univariate analysis of 22 TNBC cases, a better progression-free survival correlated significantly with a positive TLE3 expression in the tumor (p = 0.025). A multivariate logistic regression analysis including 22 patients with TNBC also showed that a positive TLE3 expression significantly correlated with a better progression-free survival (p = 0.037).
Our findings suggest that TLE3 is a useful marker for predicting the therapeutic effect of eribulin chemotherapy for TNBC.
最近开发的试剂甲磺酸艾日布林（eribulin）是一种微管动力学抑制剂，其作用机制与紫杉烷类和长春碱类药物不同。该药物被认为是治疗局部晚期或转移性乳腺癌（MBC）的一种有前途的化疗药物。在这项研究中，我们研究了肿瘤中β-微管蛋白 III 类、谷胱甘肽 S-转移酶 pi（GSTP）1 或转导蛋白样增强子分裂 3（TLE）3 的表达等变量是否可以作为预测 eribulin 化疗疗效的因素。
本研究纳入了 52 例接受 eribulin 化疗的 MBC 患者。采用免疫组化法检测雌激素受体（ER）、孕激素受体（PgR）、人表皮生长因子受体 2（HER2）、Ki67、β-微管蛋白 III 类、GSTP-1 和 TLE-3 的表达水平。
当分析三阴性乳腺癌（TNBC）病变患者的预后时，TLE3 阴性肿瘤患者的无进展生存期明显差于 TLE3 阳性肿瘤患者（p = 0.011，log-rank）。然而，在所有患者组（p = 0.433，log-rank）或非 TNBC 病变患者组（p = 0.659，log-rank）中，TLE-3 阳性/阴性患者的预后无差异。基于 22 例 TNBC 病例的单因素分析，肿瘤中 TLE3 表达阳性与较好的无进展生存期显著相关（p = 0.025）。包括 22 例 TNBC 患者的多变量 logistic 回归分析也显示，TLE3 表达阳性与较好的无进展生存期显著相关（p = 0.037）。
我们的研究结果表明，TLE3 是预测 TNBC 患者 eribulin 化疗疗效的有用标志物。
