Gynäkologie mit Brustzentrum, Charité-Universitätsmedizin Berlin, Berlin, Germany.
West German Study Group, Mönchengladbach, Germany.
Breast Cancer Res. 2020 May 14;22(1):47. doi: 10.1186/s13058-020-01283-w.
The presence of tumor-infiltrating lymphocytes has been associated with prognosis and chemotherapy response, particularly in high-risk breast cancer subtypes. There is limited data so far as to (i) how tumor-infiltrating lymphocyte (TIL) measurements correlate with genomic measurements such as the Oncotype DX Recurrence Score® and (ii) whether the survival impact of TIL measurements varies according to different adjuvant systemic therapies.
The WSG PlanB trial compared an anthracycline-free chemotherapy regimen (6x docetaxel/cyclophosphamide, TC) to an anthracycline-taxane sequence (4xEC followed by 4x docetaxel) in patients with intermediate-risk, HER2-negative early breast cancer (EBC). Patients with HR-positive HER2-negative EBC were further stratified to receive endocrine therapy alone vs. chemotherapy followed by endocrine therapy based on Recurrence Score results and nodal status. In this analysis, three independent observers quantified and categorized the presence of TILs among tumor samples from patients in PlanB. TIL measurements were correlated with clinical/pathological parameters and treatment outcome overall and according to the treatment arm.
Disease-free survival (DFS) rates were significantly better (p = .04) in HR-negative patients with high vs. intermediate TIL levels and were higher in low vs. intermediate TIL patients, however with borderline significance only (p = .06). There were no significant differences among TIL categories in HR+ patients. High RS categories, HR-negative status, and high KI67 were independently and significantly associated with high TIL categories. There was no significant impact of TIL category on DFS in patients treated by endocrine therapy only; however, in patients receiving chemotherapy, DFS in the intermediate TIL category was lower than that in the other categories.
Although the presence of high TILs is associated with negative prognostic parameters such as high KI67 and HR-negative status among patients with HR-positive HER2-negative EBC, patients with high TILs show a favorable 5-year DFS in both HR-positive/HER2-negative and triple-negative breast cancer.
肿瘤浸润淋巴细胞（TIL）的存在与预后和化疗反应相关，尤其是在高危乳腺癌亚型中。目前，关于（i）TIL 测量值与基因组测量值（如 Oncotype DX Recurrence Score®）之间的相关性，以及（ii）TIL 测量值的生存影响是否根据不同的辅助全身治疗而变化，数据有限。
WSG PlanB 试验比较了一种不含蒽环类药物的化疗方案（6x 多西他赛/环磷酰胺，TC）与蒽环类药物-紫杉烷序贯方案（4xEC 后 4x 多西他赛）在中危、HER2 阴性早期乳腺癌（EBC）患者中的疗效。HR 阳性 HER2 阴性 EBC 患者进一步根据复发评分结果和淋巴结状态分层，接受内分泌治疗或化疗后内分泌治疗。在这项分析中，三位独立观察者在 PlanB 患者的肿瘤样本中定量和分类 TIL 的存在。TIL 测量值与临床/病理参数和总体治疗结果以及治疗臂相关。
无病生存（DFS）率在 HR 阴性患者中，高 TIL 水平与中 TIL 水平相比显著更好（p=0.04），低 TIL 水平与中 TIL 水平相比也更高，但仅具有边缘显著性（p=0.06）。在 HR 阳性患者中，TIL 类别之间没有显著差异。高 RS 类别、HR 阴性状态和高 KI67 与高 TIL 类别独立且显著相关。在仅接受内分泌治疗的患者中，TIL 类别对 DFS 没有显著影响；然而，在接受化疗的患者中，中 TIL 类别的 DFS 低于其他类别。
尽管在 HR 阳性 HER2 阴性 EBC 患者中，高 TIL 与高 KI67 和 HR 阴性状态等预后不良参数相关，但高 TIL 患者在 HR 阳性/HER2 阴性和三阴性乳腺癌中均显示出有利的 5 年 DFS。
