Tissue Selection for PD-L1 Testing in Triple Negative Breast Cancer (TNBC)

Abstract

Atezolizumab in combination with nab-paclitaxel has been introduced for the treatment of locally advanced or recurrent triple negative breast cancer (TNBC). Patient selection relies on the use of immunohistochemistry using a specific monoclonal PD-L1 antibody (clone SP142) in a tightly controlled companion diagnostic test (CDx) with a defined interpretative algorithm. Currently there are no standardized recommendations for selecting the optimal tissue to be tested and there is limited data to support decision making, raising the possibility that tissue selection may bias test results. We compared PD-L1 SP142 assessment in a collection of 73 TNBC cases with matched core biopsies and excision samples. There was good correlation between PD-L1-positive core biopsy and subsequent excision, but we found considerable discrepancy between PD-L1 negative core biopsy and matched excision, with a third of cases found negative on core biopsies converting to positive upon examination of the excision tissue. In view of these findings, we developed a workflow for the clinical testing of TNBC for PD-L1 and implemented it in a central referral laboratory. We present audit data from the clinical PD-L1 testing relating to 2 years of activities, indicating that implementation of this workflow results in positivity rates in our population of TNBC similar to those of IMpassion130 clinical trial. We also developed an online atlas with a precise numerical annotation to aid pathologists in the interpretation of PD-L1 scoring in TNBC.

Comparison of assessment of programmed death-ligand 1 (PD-L1) status in triple-negative breast cancer biopsies and surgical specimens

“…For SP142 at IC score 1%, we found a positivity rate of 11% in biopsies as compared with 53% in resection specimens 12. Recently, a positivity rate of 30% in TNBC core biopsies and 52% in matching resection tissues for SP142 (IC 1%) was reported 23. Higher positivity rates of 61% (IC score 1%, CPS 1) were observed with SP263 in biopsies that is more in line with the prevalence of 75% in surgical specimens.…”

“…12 Recently, a positivity rate of 30% in TNBC core biopsies and 52% in matching resection tissues for SP142 (IC 1%) was reported. 23 Higher positivity rates of 61% (IC score 1%, CPS 1) were observed with SP263 in biopsies that is more in line with the prevalence of 75% in surgical specimens. For 22C3, the positivity rate in biopsies ranged between 32% and 38% at IC score 1% and CPS 1 that is higher as compared with TNBC biopsies of another study with 25.7% (IC 1%) but lower as compared with the matching resection specimens with 53%.…”

“…However, studies comparing different types of tissue samples for PD-L1 testing in TNBC are rare and our data suggest that tumour tissue of biopsies might be appropriate for PD-L1 assessment. In a recent study, a good correlation between PD-L1 positive (SP142 IC 1%) TNBC core biopsies and excision samples was demonstrated but discrepancy between PD-L1 negative core biopsy and matched resection with a third of cases converting to PD-L1 positivity 23. In another comparative study of lung biopsies and corresponding resected tumours, the authors reported a poor association of the PD-L1 expression using the SP142 test and pointed out that biopsies can be misleading 27…”

“…In a recent study, a good correlation between PD-L1 positive (SP142 IC 1%) TNBC core biopsies and excision samples was demonstrated but discrepancy between PD-L1 negative core biopsy and matched resection with a third of cases converting to PD-L1 positivity. 23 In another comparative study of lung biopsies and corresponding resected tumours, the authors reported a poor association of the PD-L1 expression using the SP142 test and pointed out that biopsies can be misleading. 27 Clinical trials use a mixture of tissue samples, usually featuring both biopsies and resection specimens of different locations, primary or metastatic sites and pretreated patients.…”

Diagnostic biopsy does not accurately reflect the PD-L1 expression in triple-negative breast cancer

“…Dobritoiu et al assessed the PD-L1 status in TNBC using the SP142 protocol and reported that among the analyzed biopsy specimens, 22 (30%) were PD-L1-positive and 51 (70%) PD-L1-negative [ 13 ]. Similarly to our research, upon examining the resection specimens, another 16 tumors came to be PD-L1-positive, while none of the initially PD-L1-positive tumors was reclassified as negative.…”