Molecular Immunology Unit, Institut Jules Bordet, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium.
Unit of Clinical Epidemiology, IRCCS AOU San Martino-IST, Genova, Italy.
Cancer Treat Rev. 2017 Jun;57:8-15. doi: 10.1016/j.ctrv.2017.04.005. Epub 2017 May 2.
A relationship between baseline tumor-infiltrating lymphocytes (TIL) and outcomes has been described in HER2-positive breast cancer. Nevertheless, the magnitude of this association and whether this effect differs based on the type of anti-HER2 agent remain controversial. This meta-analysis investigated the association between baseline TIL and pathologic complete response (pCR) rates in HER2-positive breast cancer patients treated with neoadjuvant chemotherapy plus trastuzumab and lapatinib either alone or in combination.
A literature search covering PubMed, Embase and the Cochrane library up to October 31, 2016 identified randomized, controlled trials investigating neoadjuvant chemotherapy plus trastuzumab and lapatinib either alone or in combination where published data for pCR based on pre-treatment TIL scores were available. Two subgroups were considered: high baseline TIL vs. non-high TIL, according to each study definition. Summary risk estimates (odds ratio) and 95% confidence intervals (CI) were calculated for pCR using pre-treatment TIL levels for each trial. Pooled analyses were conducted using random and fixed effects models. Interaction P-values were computed using a Monte Carlo permutation test.
A total of 5 studies (N=1256 patients) were included. Overall, high TIL subgroup was associated with a significantly increased pCR rate (OR 2.46; 95% CI 1.36-4.43; P=0.003). No interaction was observed between TIL subgroup (high vs. non-high TIL) and response to anti-HER2 agent(s) (trastuzumab vs. lapatinib vs. their combination; P=0.747) and chemotherapy (anthracycline and taxanes vs. taxanes only; P=0.201). A stronger association between high TIL subgroup and pCR rates was observed when examining only the 4 studies using anthracycline- and taxane- based neoadjuvant chemotherapy and the 60% cut-off for high TIL (N=869, NeoALTTO excluded) with an OR of 2.88 (95% CI 2.03-4.08; P<0.001).
In HER2-positive breast cancer, high baseline TIL are associated with increased pCR probability irrespective of neoadjuvant anti-HER2 agent(s) and chemotherapy regimens used.
在 HER2 阳性乳腺癌中，已描述了基线肿瘤浸润淋巴细胞（TIL）与结局之间的关系。然而，这种关联的程度以及这种效应是否因抗 HER2 药物的类型而异仍存在争议。本荟萃分析调查了接受新辅助化疗加曲妥珠单抗和拉帕替尼单药或联合治疗的 HER2 阳性乳腺癌患者中基线 TIL 与病理完全缓解（pCR）率之间的关联。
对 PubMed、Embase 和 Cochrane 图书馆进行文献检索，截至 2016 年 10 月 31 日，检索了新辅助化疗加曲妥珠单抗和拉帕替尼单药或联合治疗，且可获得基于治疗前 TIL 评分的 pCR 发表数据的随机对照试验。考虑了两个亚组：根据每项研究的定义，高基线 TIL 与非高 TIL。使用每个试验的治疗前 TIL 水平计算 pCR 的汇总风险估计值（比值比）和 95%置信区间（CI）。使用随机和固定效应模型进行汇总分析。使用蒙特卡罗置换检验计算交互 P 值。
共纳入 5 项研究（N=1256 例患者）。总体而言，高 TIL 亚组与 pCR 率显著增加相关（OR 2.46；95%CI 1.36-4.43；P=0.003）。未观察到 TIL 亚组（高与非高 TIL）与抗 HER2 药物（曲妥珠单抗与拉帕替尼与它们的联合）和化疗（蒽环类和紫杉烷与仅紫杉烷）之间的反应之间存在交互作用（P=0.747）。当仅检查使用蒽环类和紫杉烷类新辅助化疗和高 TIL 60%截止值的 4 项研究（N=869，排除 NeoALTTO）时，高 TIL 亚组与 pCR 率之间的关联更强，比值比为 2.88（95%CI 2.03-4.08；P<0.001）。
在 HER2 阳性乳腺癌中，高基线 TIL 与增加的 pCR 概率相关，而与新辅助抗 HER2 药物和化疗方案无关。
