Immune landscape of breast tumors with low and intermediate estrogen receptor expression
Leonie Voorwerk, Joyce Sanders, Milou S. Keusters, Sara Balduzzi, Sten Cornelissen, Maxime Duijst, Esther H. Lips, Gabe S. Sonke, Sabine C. Linn, Hugo M. Horlings, Marleen Kok
Abstract
Immune checkpoint blockade (ICB) is currently approved for patients with triple-negative breast cancer (TNBC), whereas responses to ICB are also observed in a small subgroup of Estrogen Receptor (ER)-positive breast cancer. The cut-off for ER-positivity (≥1%) is based on likelihood of endocrine treatment response, but ER-positive breast cancer represents a very heterogeneous group. This raises the question whether selection based on ER-negativity should be revisited to select patients for ICB treatment in the context of clinical trials. Stromal tumor-infiltrating lymphocytes (sTILs) and other immune parameters are higher in TNBC compared to ER-positive breast cancer, but it is unknown whether lower ER levels are associated with more inflamed tumor microenvironments (TME). We collected a consecutive series of primary tumors from 173 HER2-negative breast cancer patients, enriched for tumors with ER expression between 1 and 99% and found levels of stromal TILs, CD8 + T cells, and PD-L1 positivity in breast tumors with ER 1-9% and ER 10-50% to be comparable to tumors with ER 0%. Expression of immune-related gene signatures in tumors with ER 1-9% and ER 10-50% was comparable to ER 0%, and higher than in tumors with ER 51-99% and ER 100%. Our results suggest that the immune landscape of ER low tumors (1-9%) and ER intermediate tumors (10-50%) mimic that of primary TNBC.