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Author:
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Brasó-Maristany, Fara; Sanso Martinez, Miriam; Chic, Nuria; Martínez, Débora; González-Farré, Blanca; Sanfeliu, Esther; Peg Camara, Vicente; Vivancos Prellezo, Ana; Prat, Aleix; Saura Manich, Cristina
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Other authors:
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Institut Català de la Salut; [Brasó-Maristany F, Chic N, Martínez D] Translational Genomics and Targeted Therapies in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain. Department of Medical Oncology, Hospital Clínic of Barcelona, Barcelona, Spain. [Sansó M] Cancer Genomics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Department of Oncology and Hematology, Health Research Institute of the Balearic Islands (IdISBa), Palma de Mallorca, Spain. [González-Farré B, Sanfeliu E] Translational Genomics and Targeted Therapies in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain. Department of Pathology, Hospital Clínic de Barcelona, Barcelona, Spain. [Peg V] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Saura C] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. SOLTI Cooperative Group, Barcelona, Spain. Department of Oncology, Institut Oncològic Baselga (IOB) Institute of Oncology, Quironsalud Group, Barcelona, Spain. [Prat A] Translational Genomics and Targeted Therapies in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain. Department of Medical Oncology, Hospital Clínic of Barcelona, Barcelona, Spain. Cancer Genomics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. SOLTI Cooperative Group, Barcelona, Spain. Department of Oncology, Institut Oncològic Baselga (IOB) Institute of Oncology, Quironsalud Group, Barcelona, Spain. Department of Medicine, University of Barcelona, Barcelona, Spain. [Vivancos A] Cancer Genomics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain; Vall d'Hebron Barcelona Hospital Campus |
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Abstract:
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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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Abstract:
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This study has received funding from Instituto de Salud Carlos III—PI19/01846 (to AP), Breast Cancer Now—2018NOVPCC1294 (to AP), Breast Cancer Research Foundation-AACR Career Development Awards for Translational Breast Cancer Research 19-20-26-PRAT (to AP), Fundació La Marató TV3 201935-30 (to AP), the European Union’s Horizon 2020 research and innovation programme H2020-SC1-BHC-2018-2020 (to AP), Asociación de Cáncer de Mama Metastásico CMM_CHIARAG19_001 (to AP), Pas a Pas (to AP), Save the Mama (to AP), Fundación Científica Asociación Española Contra el Cáncer AECC_Postdoctoral17-1062 (to FB-M) and INVES19056SANS (to MiS), FERO-ghd 2020 breast cancer award (MS), and Generalitat de Catalunya Peris PhD4MD 2019 SLT008/18/00122 (to NC). |
