A low level of stromal cytotoxic T-cell infiltration in breast cancer tumor specimens predicts patients who may benefit most from antibody- vs molecular-based human epidermal growth factor receptor 2 (HER2) inhibitors, according to new research published in JAMA Oncology (published online July 27, 2017; doi:10.1001.jamaoncol.2017.2085).
Increasing research efforts have been focused on tumor-infiltrating lymphocytes in HER2-positive breast cancer and their potential association with clinical outcomes and prognostic value regarding chemotherapy and HER2-targeted therapies. Further research is needed to fully understand these relationships.
A group of Canadian researchers led by Shuzhen Liu, MD, department of pathology and laboratory medicine, Genetic Pathology Evaluation Centre, University of British Columbia (Vancouver), investigated the role of tumor-infiltrating lymphocytes in predicting outcomes in patients with HER2-positive metastatic breast cancer. Researchers were particularly focused on cytotoxic CD8+ T cells in their evaluation of tumor-infiltrating lymphocytes. A total of 647 patients from 21 countries were randomized to receive either an antibody-based (trastuzumab) or a small molecular-based (lapatinib) anti-HER2 therapy, in combination with a taxane (paclitaxel or docetaxel) for 24 weeks. Patients had received no prior chemotherapy or HER2-targeted therapy in the metastatic setting.
Tumor tissues were collected and scored for tumor-infiltrating lymphocytes on hematoxylin-eosin (H&E)-stained sections. Immunohistochemical analysis was undertaken to assess CD8, FOXP3, CD56, and programmed cell death protein 1 (PD-1) expression on stromal tumor-infiltrating lymphocytes and intratumoral lymphocytes.
The primary outcome of the study was the prognostic effects of biomarkers for progression-free survival (PFS). The median follow-up was 21.5 months.
Univariate stratified analyses showed a significant predictive effect on risk for progression with lapatinib compared with trastuzumab among patients with low CD8+ stromal tumor-infiltrating lymphocyte counts (HR, 2.94; 95% CI, 1.40-6.17; P = .003) and among the patients with high CD8+ stromal counts (HR, 1.36; 95% CI, 1.05-1.75; P = .02).
Researchers concluded that, “In this secondary analysis of a phase III randomized clinical trial, a low level of preexisting cytotoxic stromal tumor-infiltrating lymphocytes predicted the most benefit from an antibody- vs a small molecule–based drug against the same target.”—Zachary Bessette