Molecular Oncology Laboratory, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
Department of Medical Oncology, Hospital Clínic de Barcelona, Barcelona, Spain.
Ann Oncol. 2018 Jan 1;29(1):170-177. doi: 10.1093/annonc/mdx647.
The presence of stromal tumor-infiltrating lymphocytes (TILs) is associated with increased pathologic complete response (pCR) and improved outcomes in HER2-positive early-breast cancer (BC) treated with anti-HER2-based chemotherapy. In the absence of chemotherapy, the association of TILs with pCR following anti-HER2 therapy-only is largely unknown.
The PAMELA neoadjuvant trial treated 151 women with HER2-positive BC with lapatinib and trastuzumab [and hormonal therapy if hormone receptor (HR)-positive] for 18 weeks. Percentage of TILs and tumor cellularity were determined at baseline (N = 148) and at day 15 (D15) of treatment (N = 134). Associations of TILs and tumor cellularity with pCR in the breast were evaluated. A combined score based on tumor cellularity and TILs (CelTIL) measured at D15 was derived in PAMELA, and validated in D15 samples from 65 patients with HER2-positive disease recruited in the LPT109096 neoadjuvant trial, where anti-HER2 therapy-only was administer for 2 weeks, then standard chemotherapy was added for 24 weeks.
In PAMELA, baseline and D15 TILs were significantly associated with pCR in univariate analysis. In multivariable analysis, D15 TILs, but not baseline TILs, were significantly associated with pCR. At D15, TILs and tumor cellularity were found independently associated with pCR. A combined score (CelTIL) taking into account both variables was derived. CelTIL at D15 as a continuous variable was significantly associated with pCR, and patients with CelTIL-low and CelTIL-high scores had a pCR rate of 0% and 33%, respectively. In LPT109096, CelTIL at D15 was found associated with pCR both as a continuous variable and as group categories using a pre-defined cut-off (75.0% versus 33.3%).
On-treatment TILs, but not baseline TILs, are independently associated with response following anti-HER2 therapy-only. A combined score of TILs and tumor cellularity measured at D15 provides independent predictive information upon completion of neoadjuvant anti-HER2-based therapy.
NCT01973660.
在接受抗 HER2 为基础的化疗治疗的 HER2 阳性早期乳腺癌（BC）患者中，间质肿瘤浸润淋巴细胞（TILs）的存在与增加的病理完全缓解（pCR）和改善的结局相关。在没有化疗的情况下，抗 HER2 治疗后 TILs 与 pCR 的相关性在很大程度上是未知的。
PAMELA 新辅助试验用拉帕替尼和曲妥珠单抗（如果激素受体[HR]阳性，则用激素治疗）治疗 151 例 HER2 阳性 BC 患者，治疗 18 周。在基线（N=148）和治疗第 15 天（D15）（N=134）时确定 TILs 和肿瘤细胞密度的百分比。评估 TILs 和肿瘤细胞密度与乳房 pCR 的相关性。在 PAMELA 中，基于 D15 时测量的肿瘤细胞密度和 TILs （CelTIL）得出了一个综合评分，并在 LPT109096 新辅助试验中 65 例接受抗 HER2 治疗的 HER2 阳性疾病患者的 D15 样本中进行了验证，这些患者接受了 2 周的抗 HER2 治疗，然后添加 24 周的标准化疗。
在 PAMELA 中，在单变量分析中，基线和 D15 TILs 与 pCR 显著相关。在多变量分析中，D15 TILs，但不是基线 TILs，与 pCR 显著相关。在 D15，TILs 和肿瘤细胞密度被发现与 pCR 独立相关。考虑到两个变量的综合评分（CelTIL）被推导出来。D15 时的 CelTIL 作为连续变量与 pCR 显著相关，CelTIL 低值和 CelTIL 高值患者的 pCR 率分别为 0%和 33%。在 LPT109096 中，D15 时的 CelTIL 作为连续变量和使用预定义的截止值（75.0%与 33.3%）的分组类别与 pCR 相关。
治疗中的 TILs，但不是基线 TILs，与抗 HER2 治疗后仅有的反应独立相关。在完成基于抗 HER2 的新辅助治疗后，D15 时测量的 TILs 和肿瘤细胞密度的综合评分提供了独立的预测信息。
NCT01973660。
