Lester and Sue Smith Breast Center and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas.
Department of Medicine, Baylor College of Medicine, Houston, Texas.
Clin Cancer Res. 2020 Feb 1;26(3):738-745. doi: 10.1158/1078-0432.CCR-19-1402. Epub 2019 Oct 25.
Tumor-infiltrating lymphocytes (TIL) are associated with benefit to trastuzumab and chemotherapy in patients with early-stage HER2 breast cancer. The predictive value of TILs, TIL subsets, and other immune cells in patients receiving chemotherapy-sparing lapatinib plus trastuzumab treatment is unclear. Hematoxylin and eosin-stained slides ( = 59) were used to score stromal (s-)TILs from pretreatment biopsies of patients enrolled in the neoadjuvant TBCRC006 trial of 12-week lapatinib plus trastuzumab therapy (plus endocrine therapy for ER tumors). A 60% threshold was used to define lymphocyte-predominant breast cancer (LPBC). Multiplexed immunofluorescence (m-IF) staining (CD4, CD8, CD20, CD68, and FoxP3) and multispectral imaging were performed to characterize immune infiltrates in single formalin-fixed paraffin-embedded slides ( = 33).
The pathologic complete response (pCR) rate was numerically higher in patients with LPBC compared with patients with non-LPBC (50% vs. 19%, = 0.057). Unsupervised hierarchical clustering of the five immune markers identified two patient clusters with different responses to lapatinib plus trastuzumab treatment (pCR = 7% vs. 50%, for cluster 1 vs. 2 respectively; = 0.01). In multivariable analysis, cluster 2, characterized by high CD4, CD8, CD20 s-TILs, and high CD20 intratumoral TILs, was independently associated with a higher pCR rate ( = 0.03). Analysis of single immune subpopulations revealed a significant association of pCR with higher baseline infiltration by s-CD4, intratumoral (i-) CD4, and i-CD20 TILs.
LPBC was marginally associated with higher pCR rate than non-LPBC in patients with lapatinib plus trastuzumab treated HER2 breast cancer. Quantitative assessment of the immune infiltrate by m-IF is feasible and may help correlate individual immune cell subpopulations and immune cell profiles with treatment response.
浸润肿瘤的淋巴细胞（TIL）与早期 HER2 乳腺癌患者接受曲妥珠单抗和化疗的获益相关。在接受化疗药物节省的拉帕替尼联合曲妥珠单抗治疗的患者中，TIL、TIL 亚群和其他免疫细胞的预测价值尚不清楚。从参加新辅助 TBCRC006 试验的患者的预处理活检中使用苏木精和伊红染色（=59）来评分基质（s-）TILs，该试验接受 12 周的拉帕替尼联合曲妥珠单抗治疗（ER 肿瘤加内分泌治疗）。使用 60%的阈值来定义淋巴细胞为主型乳腺癌（LPBC）。进行多重免疫荧光（m-IF）染色（CD4、CD8、CD20、CD68 和 FoxP3）和多光谱成像，以在单个福尔马林固定石蜡包埋切片中对免疫浸润物进行特征化（=33）。
与非 LPBC 患者相比，LPBC 患者的病理完全缓解（pCR）率略高（50% vs. 19%，=0.057）。对五种免疫标志物进行无监督层次聚类，确定了两个具有不同拉帕替尼加曲妥珠单抗治疗反应的患者簇（pCR=7% vs. 50%，分别为簇 1 和簇 2；=0.01）。在多变量分析中，以高 CD4、CD8、CD20 s-TIL 和高 CD20 肿瘤内 TIL 为特征的簇 2 与更高的 pCR 率独立相关（=0.03）。对单个免疫亚群的分析显示，基线 s-CD4、肿瘤内（i-）CD4 和 i-CD20 TIL 的浸润与 pCR 显著相关。
与非 LPBC 患者相比，接受拉帕替尼加曲妥珠单抗治疗的 HER2 乳腺癌患者中，LPBC 与更高的 pCR 率略有相关。通过 m-IF 对免疫浸润物进行定量评估是可行的，并且可能有助于将单个免疫细胞亚群和免疫细胞谱与治疗反应相关联。
