Do Cytotoxic TILs Predict Response to Therapy in HER2-Positive Breast Cancer?


Researchers examined whether low levels of pre-existing cytotoxic tumor-infiltrating lymphocytes can predict the response to antibody- and molecule-based drugs in metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer, published in JAMA Oncology (online November 9, 2017; doi:10.1001/jamaoncol.2017.2085).

A wealth of evidence suggests that tumor-infiltrating lymphocytes are associated with clinical outcomes in patients with HER2-positive breast cancer. Whether or not these lymphocytes are predictive of the efficacy of various chemotherapy and HER2-targeting therapies is in need of further research.

A group of Canadian researchers led by Shuzhen Liu, MD, Genetic Pathology Evaluation Center, University of British Columbia, investigated the role of cytotoxic CD8-positive T-cells in predicting outcomes in patients with HER2-positive metastatic breast cancer receiving either trastuzumab or lapatinib therapy. A total of 647 patients from 21 countries were included in the phase III trial and randomized to receive either treatment 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.

Among the total patient population, 614 had tumor tissue samples scored for hematoxylin-eosin (H&E)-stained section stromal tumor-infiltrating lymphocytes and 427 had tumor samples scored for CD8 biomarker assessments.


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Researchers reported that H&E stromal tumor-infiltrating lymphocyte counts of more than 5% were observed in 35% of cases (n = 215), but did not show significant prognostic effects. Univariate stratified analyses identified a significant predictive effect on risk for progression with lapatinib, compared with trastuzumab, among patients with low CD8-positive stromal tumor-infiltrating lymphocyte counts. No other immunohistochemistry biomarkers were associated with prognostic effects.

In their concluding remarks, researchers stated that a low level of pre-existing cytotoxic stromal tumor-infiltrating lymphocytes predict the most benefit from an antibody-based drug for metastatic HER2-positive breast cancer. “Implementation of standardized evaluation of cytotoxic T-cell infiltration may be valuable for predicting response to antibody-based therapies,” they wrote.—Zachary Bessette