Immune biomarkers and treatment (tx) outcome in hormone receptor-positive (HR+) breast cancer (BC) patients (pts) treated with preoperative chemotherapy (preop chemo) plus bevacizumab (bev).

Abstract

e12134 Background: Though preliminary study of the BC immune microenvironment suggests that HR+ tumors are less immune-active than other subtypes, immune biomarkers may have important clinical implications in HR+ BC pts. Methods: 78 HR+/HER2- BC pts were enrolled on a prospective trial of preop bev followed by bev with adriamycin/cyclophosphamide/paclitaxel dose-dense chemo. Tumor samples were collected at diagnosis and surgery (pre-tx and post-tx). PD-L1 expression (by immunohistochemistry) and tumor-infiltrating lymphocytes (TILs) were scored. Whole transcriptome sequencing and Nanostring PanCancer Immune Profiling Panel were performed. Pathologic response at surgery was assessed by Miller-Payne (MP) and residual cancer burden (RCB) scores. We calculated adjusted correlations by linear/logistic regression for RCB/dichotomized MP, respectively. Results: 55 pts who received trial tx and had >1 analyzable specimen are included. Pre-tx TILs and tumor PD-L1 (tPD-L1) scores (see table) were slightly positively correlated (Spearman rho 0.23, p=0.1). Large changes (>5%) in TILs or tPD-L1 from pre-tx to post-tx were rare: 2 pts each had large changes in TIL or tPD-L1 score (N=38 and N=31 pairs, respectively). Higher pre-tx TILs or tPD-L1 were significantly associated with more favorable RCB and MP (all Spearman p<0.01) in unadjusted analyses. After adjustment for age and tumor grade, higher pre-tx TILs and tPD-L1 were associated with more favorable RCB (p<0.01 for both), and higher pre-tx tPD-L1 correlated with more favorable MP (p=0.03). Pathologic complete response occurred in 4 pts; all 4 had high pre-tx TILs, pre-tx tPD-L1, or both. Analysis of immune-related RNA signatures is ongoing. Conclusions: High levels of tumor-immune interaction were seen in only a minority of untreated HR+ breast tumors, and did not typically change after tx with chemo plus bev. Nonetheless, TILs and tPD-L1 are significantly associated with pathologic response to preop tx in HR+ disease. [Table: see text]