Tumor infiltrating lymphocytes predict better DFS from intense dose-dense (idd) EPC regimen – results from the German Adjuvant Intergroup Node-positive Study (GAIN-1)

Immune infiltration in breast cancer (BC) may influence the prognosis and response to systemic therapies. The association and prognostic role of tumor infiltrating lymphocytes (TILs), PD-1 and PD-L1 expression were investigated.

The adjuvant phase III GAIN-1 trial compared two dose-dense regimens, iddEPC (epirubicin (E), paclitaxel (P), cyclophosphamide (C)) vs. EC-PC (capecitabine (C)) and Ibandronate vs. observation in patients with node-positive primary breast cancer. 1318 FFPE tumor samples were assessed for TILs (HE), PD-1 and PD-L1 by immunohistochemistry. We analyzed the association of immune parameters and their prognostic and potential predictive role by Cox regression models.

Increased TILs, PD-1 and PD-L1 positive TILs were significantly associated with higher grade, higher Ki67, ER/PR negative and triple negative BC (each p < 0.0001). TILs and PD-L1 positive TILs were more frequent in HER2 positive BC (p = 0.005). At multivariate Cox regression analysis, TILs had a significant positive impact on DFS in the iddEPC-arm (HR = 0.57 [0.39 – 0.84], p = 0.0043) but not in the EC-PC-arm (HR = 1.26 [0.86 – 1.87], p = 0.2384, interaction p = 0.0336). Especially, HR+/HER2- BC with TILs treated with iddEPC had a better DFS compared to no TILs (HR = 0.59 [0.38 – 0.93], p = 0.0227). TNBC patients with PD-1 positive TILs had a significant better DFS (HR = 0.50 [0.25 – 0.99], p = 0.0457). PD-L1 had no prognostic impact.

TILs and immune checkpoints are common in high-grade, highly proliferative, triple negative and in part in HER2 positive BC. TILs predict the benefit from intense dose-dense EPC whereas the prevalence and prognostic impact of PD-1/PD-L1 seem to play an inferior role in this node-positive breast cancer cohort with adjuvant chemotherapy.