Associations in tumor infiltrating lymphocytes between clinicopathological factors and clinical outcomes in estrogen receptor-positive/human epidermal growth factor receptor type 2 negative breast cancer
Associations in tumor infiltrating lymphocytes between clinicopathological factors and clinical outcomes in estrogen receptor-positive/human epidermal growth factor receptor type 2 negative breast cancer
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DOI：
10.3892/ol.2018.9853
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发表时间：
2019-02-01
期刊：
影响因子：
2.9
通讯作者：
Yamashita, Hiroko
中科院分区：
文献类型：
--
作者：
Miyoshi, Yuichiro;Shien, Tadahiko;Yamashita, Hiroko
在雌激素受体(ER)阳性/人表皮生长因子受体2型(HER2)阴性的乳腺癌中，肿瘤浸润性淋巴细胞(TILs)的评估价值尚未确定。在本研究中，共有184例患者在初次手术后5年内发现早期远处复发，134例在5年或更长时间后被诊断为晚期远处复发，321例对照在9个机构登记的ER阳性/HER2阴性乳腺癌的初始治疗后10年内未复发。研究TIL的分布及其临床意义。TIL在早期组、晚期组和无复发组之间的分布没有显著差异，采用30%的截断点作为二分变量。在接受辅助化疗和内分泌治疗的患者中，早期复发组与采用30%分界点的无复发组相比，TIL比例有升高的趋势(P=0.064)。无复发组TIL分布与淋巴结转移(P=0.004)、ER状态(P=0.045)、孕激素受体状态(P=0.002)、肿瘤分级(P=0.021)及Ki67标记指数(P=0.002)显著相关(P=0.002，P=0.023)。高TIL分布也预示着复发后生存时间较短(P=0.026)。然而，在多因素分析中，这些预后交互作用并不显著(P=0.200)。目前的回顾性研究表明，TIL比例和复发时间之间没有显著的交互作用。然而，在具有侵袭性生物学表型的乳腺癌患者中观察到更高的TIL比例，这些患者往往对化疗更敏感。间质TIL用于确定哪些患者可能从额外治疗中受益的临床相关性值得在更大的患者群体中进一步研究。
The value of assessing tumor infiltrating lymphocytes (TILs) in estrogen receptor (ER) positive/human epidermal growth factor receptor type 2 (HER2) negative breast cancer has yet to be determined. In the present study, a total of 184 cases with early distant recurrence detected within 5 years following the primary operation, 134 with late distant recurrence diagnosed following 5 years or longer and 321 controls without recurrence for >10 years following starting the initial treatment for ER-positive/HER2 negative breast cancer, registered in 9 institutions, were analyzed. The distributions of TILs and their clinical relevance were investigated. TIL distributions did not differ significantly among the early, late and no recurrence groups, employing a 30% cut-off point as a dichotomous variable. In those who had received adjuvant chemotherapy as well as endocrine therapy, a trend toward higher TIL proportions was detected when the early recurrence group was compared with the no recurrence group employing the 30% cut-off point (P=0.064). The TIL distributions were significantly associated with nodal metastasis (P=0.004), ER status (P=0.045), progesterone receptor (PgR) status (P=0.002), tumor grade (P=0.021), and the Ki67 labeling index (LI) (P=0.002) in the no recurrence group and with the Ki67 LI in the recurrence groups (P=0.002 in early recurrence group, P=0.023 in late recurrence group). High TIL distributions also predicted shorter survival time following the detection of recurrence (P=0.026). However, these prognostic interactions were not significant in multivariate analysis (P=0.200). The present retrospective study demonstrated no significant interaction between TIL proportions and the timing of recurrence. However, higher TIL proportions were observed in breast cancer patients with aggressive biological phenotypes, which tended to be more responsive to chemotherapy. The clinical relevance of stromal TILs for identifying patients who would likely benefit from additional therapies merits further investigation in a larger patient population.