PDl1 Expression in Triple-Negative Breast Cancer is Associated with Tumour-Infiltrating Lymphocytes and Improved Outcome

Purpose: Triple-negative breast cancer lacks expression of estrogen receptor, progesterone receptor and human epidermal growth factor receptor and patients generally have a poor outcome; there is a pressing need to identify more effective therapeutic strategies. Clinical trials targeting PD1/PDL1 in melanoma and non-small cell lung cancer have reported high response rates, and tumoural PDL1 expression has been suggested as a potential biomarker to enrich for patient response to these treatments. There is only very limited data to date reporting the expression of PDL1 in triple-negative breast cancer. This study characterises PDL1 expression patterns and tumour-infiltrating lymphocytes in primary triple-negative breast cancer. Methods: PDL1 immunohistochemistry was performed on 163 primary triple-negative breast cancers and assessed in the tumour (membranous and cytoplasmic compartments) as well as immune cells in the stromal compartment. Tumour-infiltrating lymphocytes were also assessed using a standard semi-quantitative method. Samples were considered PDL1 positive if ≥1% of cells showed PDL1 expression in any compartment. Results: PDL1 expression was very common in triple-negative breast cancer, seen in 94.4% of assessable samples and was expressed in the tumour membranous (63.4%), cytoplasmic (77.6%) and stromal (92.5%) cellular compartments, with 22.1% of samples showing stromal immune cell PDL1 expression in the absence of tumoural PDL1 expression. There was a strong association between tumour-infiltrating lymphocytes and stromal PDL1 expression. While both PDL1 expression and tumour-infiltrating lymphocytes were associated with a better outcome, only tumour-infiltrating lymphocytes were independently prognostic. Conclusion: While PDL1 expression is frequent in triple-negative breast cancer, only tumour-infiltrating lymphocytes were independently prognostic suggesting that this is a major driver of outcome in these tumors. However, given the high expression levels of putative biomarkers of response to immune checkpoint therapy, these data provide support for the further investigation of PD1/PDL1 targeted therapies in triple-negative breast cancer.