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Distribution of microsatellite instability (MSI), tumor mutational load (TML) and PD-L1 status in molecularly profiled invasive breast cancer | Caris Life Sciences
Elias Obeid, Angela Ellerbrock, Elizabeth Handorf, Lori Goldstein, Zoran Gatalica, Sandra M. Swain, Claudine Isaacs, Jeff Vacirca, David Arguello, Antoinette Tan, Lee Schwartzberg
Recent data indicate a promising response to immune check point blockade (ICB) in patients with breast cancer (BC).
Pembrolizumab, a monoclonal antibody against programmed death 1 (PD-1) receptor and one of several ICB agents in development, received FDA approval for all MSI (microsatellite instability)-high solid tumors.
MSI incidence in breast cancer is not fully elucidated. Other biomarkers being explored in possible relationship to ICB activity include PD-1 ligand (PD-L1) status and tumor mutational load (TML).
In this study, we aimed to explore the incidence of these biomarkers in invasive breast cancers.
A retrospective data analysis of breast cancer patients profiled by commercial next-generation sequencing (NGS) at Caris Life Sciences was performed.
MSI was calculated by comparing repeat-insertions or deletions across over 7,000 microsatellite sequences in the patient sample to the hg19 reference genome.
Samples with repeat variances in more than 45 microsatellites were classified as MSI-High.
PD-L1 expression was evaluated using immunohistochemical analysis (IHC), with clone SP-142 (Roche Diagnostics). A sample was considered positive (PD-L1+) if there was >5% membranous staining of tumor cells.
TML (tumor mutation load) was calculated as a total number of non-synonymous somatic mutations identified per megabase of genome coding area with high being greater than or equal to 17.
A total of 9,627 BC cases were queried from Caris Life Sciences database.
5,202 tested for PD-L1 status (354 PD-L1+, 6.8%, CI 6.2-7.5%).
Of all queried cases, 1,952 tumors were tested for all three biomarkers of interest in ICB: PD-L1, MSI status, and TML: Details are presented next.
PD-L1-positivity, MSI-H, or TML-H was present in 189 cases (9.7%). At least one of the three aforementioned biomarker results was present in 7.3% of ER/PR+ cases, 10% of HER2+ , and 13% of TNBC . The majority of this was PD-L1+ and TML-H (6.1% and 3.7%), while low MSI-H distribution (0.6%).
We observed statistically significant differences in PD-L1 and TML distributions based on molecular subtype, specimen site, distant metastatic site, and age. This was not observed with MSI.
No differences in distribution were observed based on AR status in TNBC cases.
PD-L1 distribution was higher in TNBC cases, while TML was higher in ER/PR+ cases. • TML-H in lobular breast cancer (13.7%) was noted, warranting further research .
Future research is needed to show the clinical utility of these biomarkers in response to ICB and should be considered in designing prospective clinical trials.
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