AI Article Synopsis

  • Atezolizumab, an immune checkpoint inhibitor, is usually approved for PD-L1-positive triple-negative breast cancer (TNBC), but it hasn’t shown effectiveness in PD-L1-negative cases until now.
  • A case study revealed a woman with PD-L1-negative TNBC and low tumor infiltrating lymphocytes who responded remarkably well to atezolizumab alone, and an even better response when combined with nab-paclitaxel.
  • Comprehensive genomic analysis of her tumor indicated high tumor mutational burden and other specific genetic markers, suggesting these factors may help predict responses to immunotherapy in TNBC, pointing towards the need for further research on biomarkers beyond PD-L1 expression.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8489403PMC
http://dx.doi.org/10.3389/fonc.2021.710596DOI Listing

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