Review of immune checkpoint blockade and PD-L1 testing in breast cancer

In the past two decades, several drugs have been developed to modulate the immune checkpoints. These modulators regulate, amongst others, the T-cell mediated immune response and may be involved in the escape from immune surveillance. Mounting evidence in several solid tumours points towards the effectiveness of immune checkpoint blockade (ICB) therapy used either as monotherapy or in combination with conventional chemotherapy. In breast cancer, ICB therapy is effective in the treatment of triple negative breast cancer (TNBC). Several PD-L1 companion diagnostic tests have been developed for the selection of patients more likely to benefit from this treatment. Currently, two PD-L1 assays are approved for clinical use in TNBC patients: the SP142 CDx for the use of atezolizumab and the 22C3 PharmDx for the use of pembrolizumab. This review provides the background of PD-L1 testing in breast cancer and discusses the analytical performance of these tests, their scoring algorithms and inter-observer concordance and outlines best practice, including tissue selection, tools for interpretation and use of controls.