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Diagnostic Pathology
Published in: Diagnostic Pathology 1/2020

Open Access 01-12-2020 | Breast Cancer | Research

High tumor mutation burden is associated with DNA damage repair gene mutation in breast carcinomas

Authors: Ping Mei, C. Eric Freitag, Lai Wei, Yunxiang Zhang, Anil V. Parwani, Zaibo Li

Published in: Diagnostic Pathology | Issue 1/2020

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Abstract

Background

Immunotherapy has demonstrated encouraging clinical benefits in patients with advanced breast carcinomas and Programmed death ligand 1 (PD-L1) expression has been proposed as an immunotherapy biomarker. Challenges with current PD-L1 testing exist and tumor mutation burden (TMB) is emerging as a biomarker to predict clinical response to immunotherapy in melanoma and non-small cell lung cancer patients. However, TMB has not been well characterized in breast carcinomas.

Methods

The study cohort included 62 advanced breast cancer patients (13 primary and 49 metastatic). Genetic alterations and TMB were determined by FoundationOne CDx next generation sequencing (NGS) and the association with clinicopathologic features was analyzed.

Results

High TMB was observed in a relatively low frequency (3/62, 4.8%). TMB levels were positively associated tumor infiltrating lymphocytes and significantly higher TMB was observed in breast carcinomas with DNA damage repair gene mutation(s). There was no significant association between TMB levels and other analyzed clinicopathologic characteristics.

Conclusions

Our data indicate the importance of DNA damage repair proteins in maintaining DNA integrity and immune reaction and breast carcinoma patients with DDR mutation may benefit from immunotherapy.
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Metadata
Title
High tumor mutation burden is associated with DNA damage repair gene mutation in breast carcinomas
Authors
Ping Mei
C. Eric Freitag
Lai Wei
Yunxiang Zhang
Anil V. Parwani
Zaibo Li
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2020
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/s13000-020-00971-7

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