Prognostic significance of tumor-infiltrating lymphocytes may differ depending on Ki67 expression levels in estrogen receptor-positive/HER2-negative operated breast cancers
Prognostic significance of tumor-infiltrating lymphocytes may differ depending on Ki67 expression levels in estrogen receptor-positive/HER2-negative operated breast cancers
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DOI：
10.1007/s12282-019-00977-0
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发表时间：
2019-11-01
期刊：
影响因子：
4
通讯作者：
Miyoshi, Yasuo
中科院分区：
文献类型：
--
作者：
Fujimoto, Yukie;Watanabe, Takahiro;Miyoshi, Yasuo
背景肿瘤浸润性淋巴细胞(TILs)在雌激素受体(ER)阴性、人上皮生长因子受体2(HER2)阴性或HER2阳性的乳腺癌中的预后意义已被证实，但其在ER+/HER2亚型中的作用尚不清楚。根据肿瘤内面积的比例将TIL分为三组：低(10%)、中(10%-50%)和高(50%)。结果尽管所有患者TIL水平与无瘤生存期和总生存期无明显相关性，但在Ki67高表达组(n=238，p=0.035)中，高TIL表达与良好的DFS显著相关，而在Ki67低表达组(n=470，p=0.46)，高TIL表达与无瘤生存期无关。多变量分析显示，在Ki67高发组中，高TIL是DFS的显著独立因素(HR0.34；95%CI0.10-0.87；p=0.023)。在ER+/HER2-亚型中，高TIL在Ki67高表达组显示良好的DFS，但差异无统计学意义(p=0.027)；相反，Ki67低表达组的DFS较差(p=0.027)。结论在Ki67高表达的乳腺癌中，高TIL与良好的DFS相关，与ER+/HER2-亚型无关，但在Ki67低表达组和ER+/HER2-亚型中，高TIL水平与较差的DFS相关。这些结果突出了Ki67高和低乳腺癌之间TIL预后意义的差异，特别是对于ER+/HER2-亚型。
Background The prognostic significance of tumor-infiltrating lymphocytes (TILs) has been established in breast cancers with estrogen receptor (ER)-negative and human epithelial growth factor receptor 2 (HER2)-negative or HER2-positive subtypes; however, its utility concerning the ER + /HER2-subtype remains unclear.Methods We evaluated the prognostic value of TILs by analyzing 717 invasive breast cancer operation cases. TILs were classified into three groups based on the proportion of area within the tumor: low (< 10%), intermediate (10-50%), and high (> 50%). Disease-free survival (DFS) and overall survival (OS) were calculated according to TIL levels.Results Although there was no significant association between TIL levels and DFS or OS in all patients, high TILs were significantly associated with favorable DFS in Ki67-high (n = 238, p = 0.035) but not in Ki67-low (n = 470, p = 0.46) breast cancers. Multivariable analysis showed that high TILs were a significant and independent factor for DFS (HR 0.34; 95% CI 0.10-0.87; p = 0.023) among the Ki67-high group. In the ER + /HER2 - subtype, high-TILs showed favorable DFS in the Ki67-high group, although this was not statistically significant (p = 0.48); in contrast, unfavorable DFS was observed in the Ki67-low group (p = 0.027).Conclusions In Ki67-high breast cancers, high TILs were associated with favorable DFS, irrespective of subtype, but increasing TIL levels correlated with worse DFS in the Ki67-low group with the ER + /HER2 -subtype. These results highlight variation in TIL prognostic significance between Ki67-high and -low breast cancers, particularly for the ER + /HER2 - subtype.