Case Report: A Case Study Documenting the Activity of Atezolizumab in a PD-L1-Negative Triple-Negative Breast Cancer
Fara Brasó-Maristany1,2, Miriam Sansó3,4, Nuria Chic1,2
1Translational Genomics and Targeted Therapies in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.
Abstract:
The immune checkpoint inhibitor atezolizumab is approved for PD-L1-positive triple-negative breast cancer (TNBC). However, no activity of atezolizumab in PD-L1-negative TNBC has been reported to date. Here, we present the case study of a woman with TNBC with low tumor infiltrating lymphocytes and PD-L1-negative disease, which achieved a significant response to atezolizumab monotherapy and durable response after the combination of atezolizumab and nab-paclitaxel. The comprehensive genomic analysis that we performed in her tumor and plasma samples revealed high tumor mutational burden (TMB), presence of the APOBEC genetic signatures, high expression of the tumor inflammation signature, and a HER2-enriched subtype by the PAM50 assay. Some of these biomarkers have been shown to independently predict response to immunotherapy in other tumors and may explain the durable response in our patient. Our work warrants further translational studies to identify biomarkers of response to immune checkpoint inhibitors in TNBC beyond PD-L1 expression and to better select patients that will benefit from immunotherapy.
Insights
A patient with PD-L1-negative triple-negative breast cancer (TNBC) responded well to atezolizumab. Genomic analysis revealed biomarkers like high tumor mutational burden (TMB) that may predict immunotherapy response in TNBC.
Area of Science:
- Oncology
- Immunotherapy
- Genomics
Background:
- Immune checkpoint inhibitors like atezolizumab are approved for PD-L1-positive triple-negative breast cancer (TNBC).
- Limited data exists on atezolizumab efficacy in PD-L1-negative TNBC.
- Predictive biomarkers beyond PD-L1 expression are needed for patient selection.
Observation:
- A case study of a patient with PD-L1-negative TNBC and low tumor-infiltrating lymphocytes was presented.
- The patient achieved a significant response to atezolizumab monotherapy.
- A durable response was observed after combining atezolizumab with nab-paclitaxel.
Findings:
- Comprehensive genomic analysis revealed high tumor mutational burden (TMB) in the tumor and plasma samples.
- APOBEC genetic signatures and a high tumor inflammation signature were detected.
- The tumor was classified as HER2-enriched subtype by PAM50 assay.
Implications:
- High TMB, APOBEC signatures, and inflammation signatures may predict response to atezolizumab in TNBC.
- These findings suggest potential biomarkers beyond PD-L1 for immunotherapy selection in TNBC.
- Further translational studies are warranted to validate these biomarkers and optimize patient selection for immunotherapy.
