Pembrolizumab and Trastuzumab in High Tumor Mutational Burden and POLE-Mutated HER2-Positive Refractory Breast Cancer.

Abstract

Metastatic breast cancer (mBC) is an incurable disease, and it is not sensitive to immunotherapy due to its low immunogenicity. Recently, inactivated DNA polymerase epsilon (POLE) mutations have been found to be associated with high tumor mutational burden (TMB), which is an effective immuno-oncology biomarker. Patients with POLE mutations with different types of cancer have properly responded to immunotherapy. We aimed to report the first case of programmed death-ligand 1 (PD-L1)-negative mBC presenting with high TMB and POLE mutations, in which a complete response to 5 cycles of chemotherapy and 1 year of pembrolizumab and trastuzumab was noted after failing several lines of HER2-targeted therapies. Our findings also suggest that biomarker-driven patient selection is highly significant for further clinical development of combination therapies via anti-HER2 plus immune-checkpoint inhibitors for HER2+ BC patients.

• Authors: Li Zhang, Yimeng Chen, Yao Lv, Shunchang Jiao, Weihong Zhao
• Journal: The oncologist (Oncologist) Vol. 27 Issue 4 Pg. 245-250 (04 05 2022) ISSN: 1549-490X [Electronic] England
• PMID: 35380719 (Publication Type: Case Reports, Journal Article)
• Copyright: © Crown copyright 2022.

Chemical References

• Antibodies, Monoclonal, Humanized
• B7-H1 Antigen
• Biomarkers, Tumor
• Poly-ADP-Ribose Binding Proteins
• pembrolizumab
• DNA Polymerase II
• POLE protein, human
• Trastuzumab

Topics

• Antibodies, Monoclonal, Humanized (therapeutic use)
• B7-H1 Antigen (genetics)
• Biomarkers, Tumor (genetics)
• Breast Neoplasms (drug therapy, genetics, pathology)
• DNA Polymerase II (genetics)
• Female
• Humans
• Immunotherapy
• Poly-ADP-Ribose Binding Proteins (genetics)
• Trastuzumab (therapeutic use)