A Prognostic Model Based on Residual Cancer Burden and Tumor-Infiltrating Lymphocytes on Residual Disease after Neoadjuvant Therapy in HER2+Breast Cancer

Purpose: We aim to evaluate the prognostic significance of tumor-infiltrating lymphocyte on residual disease (RD-TIL) in HER2+ patients with breast cancer who failed to achieve pathologic complete response (pCR) after anti-HER2+ chemotherapy (CT)-based neoadjuvant treatment (NAT). We assessed the feasibility of combining the prognostic information provided by residual cancer burden (RCB) and RD-TILs into a composite score (RCB+TIL).Experimental Design: HER2+ patients with breast cancer trea-ted with CT+anti-HER2-based NAT at three institutions were retrospectively included. RCB and TIL levels were evaluated on hematoxylin and eosin-stained slides from surgical samples accord-ing to available recommendations. Overall survival (OS) was used as an outcome measure.Results: A total of 295 patients were included, of whom 195 had RD. RCB was significantly associated with OS. Higher RD-TILs were significantly associated with poorer OS as compared with lower RD-TILs (15% cutoff). In multivariate analysis, both RCB and RD-TIL maintained their independent prognostic value. A com-bined score, RCB+TIL, was calculated from the estimated coeffi- cient of RD-TILs and the RCB index in a bivariate logistic model for OS. The RCB+TIL score was significantly associated with OS. The C-index for OS of the RCB+TIL score was numerically higher than that of RCB and significantly higher than that of RD-TILs.Conclusions: We have reported an independent prognostic impact of RD-TILs after anti-HER2+CT NAT, which might under-lie an imbalance of the RD microenvironment towards immuno-suppressive features. We provided a new composite prognostic score based on RCB+TIL, which was significantly associated with OS and proved to be more informative than the isolated evaluation of RCB and RD-TILs.