Tumor-Infiltrating Lymphocytes in a Contemporary Cohort of Women with Ductal Carcinoma In Situ (DCIS)
Tumor-Infiltrating Lymphocytes in a Contemporary Cohort of Women with Ductal Carcinoma In Situ (DCIS)
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DOI：
10.1245/s10434-019-07562-x
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发表时间：
2019-10-01
影响因子：
3.7
通讯作者：
Roses, Daniel
中科院分区：
文献类型：
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作者：
Darvishian, Farbod;Ozerdem, Ugur;Roses, Daniel
越来越多的证据表明，肿瘤免疫微环境影响乳腺癌的发生和预后。浸润性乳腺癌中肿瘤浸润淋巴细胞（TIL）的密度与治疗反应相关，特别是在三阴性疾病中。乳腺导管原位癌（DCIS）中TIL的临床相关性和结局尚不清楚。方法对2010年至2018年668例单纯DCIS患者的机构数据库进行查询。TILs按照国际TILs工作组指南进行评价。从接触基底膜的基质的一个高倍视野中的致密病灶（热点）评估TIL的百分比。统计方法包括聚类分析（定义稀疏与密集TIL）、逻辑和考克斯回归模型。结果69例DCIS和TILs患者接受了评估，其中54例（78%）接受了保乳手术。13例（19%）患者出现同侧复发。根据手术日期，将每例复发（n = 13）与4例对照（n = 56）进行匹配。中位随访时间为6.7年。TIL被定义为稀疏（< 45%）或密集（>= 45%）。致密型TIL与年龄较轻（p = 0.045）、肿瘤大小较大（p < 0.001）、核分级较高（p = 0.010）、粉刺组织学（p = 0.033）、坏死（p = 0.027）、雌激素受体（ER）阴性（p = 0.037）和同侧复发（p = 0.001）相关。9例密集型TIL患者的平均复发时间为73.5个月，而4例稀疏型TIL患者的平均复发时间为97.9个月（p = 0.003）。结论致密TIL与年龄、肿瘤大小、核分级、粉刺组织学、坏死和ER状态显著相关，是单纯DCIS患者复发的重要预测因子。
Background Growing evidence suggests that the tumor immune microenvironment influences breast cancer development and prognosis. Density of tumor-infiltrating lymphocytes (TILs) within invasive breast cancer is correlated with response to therapy, especially in triple-negative disease. The clinical relevance and outcomes of TILs within ductal carcinoma in situ (DCIS) are less understood. Methods Our institutional database of 668 patients with pure DCIS from 2010 to 2018 was queried. TILs were evaluated by International TILs Working Group guidelines. Percentage of TILs was assessed from the densest focus (hotspot) in one high-power field of stroma touching the basement membrane. Statistical methods included cluster analyses (to define sparse versus dense TILs), logistic, and Cox regression models. Results Sixty-nine patients with DCIS and TILs were evaluated, of whom 54 (78%) were treated by breast-conserving surgery. Thirteen (19%) patients had ipsilateral recurrence. Each recurrence (n = 13) was matched to four controls (n = 56) based on date of surgery. Median follow-up was 6.7 years. TILs were defined as sparse (< 45%) or dense (>= 45%). Dense TILs were associated with younger age (p = 0.045), larger tumor size (p < 0.001), high nuclear grade (p = 0.010), comedo histology (p = 0.033), necrosis (p = 0.027), estrogen receptor (ER) negativity (p = 0.037), and ipsilateral recurrence (p = 0.001). Nine patients with dense TILs had mean time to recurrence of 73.5 months compared with four patients with sparse TILs with mean time to recurrence of 97.9 months (p = 0.003). Conclusions Dense TILs were significantly associated with age, tumor size, nuclear grade, comedo histology, necrosis, and ER status and was a significant predictor of recurrence in patients with pure DCIS.