Research Perspectives:

Tumor mutational burden as a predictor of immunotherapy response in breast cancer

Tess A. O’Meara and Sara M. Tolaney _

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Oncotarget. 2021; 12:394-400. https://doi.org/10.18632/oncotarget.27877

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Tess A. O’Meara1 and Sara M. Tolaney2

1 Department of Internal Medicine, Brigham and Women’s Hospital, Boston, MA, USA

2 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

Correspondence to:

Sara M. Tolaney,email: [email protected]

Keywords: breast cancer; immunotherapy; tumor mutational burden

Received: January 09, 2021     Accepted: January 19, 2021     Published: March 02, 2021

Copyright: © 2021 O’Meara and Tolaney. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Tumor mutational burden (TMB) is a promising tool to help define patients with triple-negative breast cancer (TNBC) most likely to benefit from immune checkpoint blockade (ICB) therapies. Roughly reflecting the degree of neo-antigens that tumors present to immune cells, TMB associates with multiple measures of tumoral immunogenicity and has proven clinically useful in cancers with relatively high mutation burden. TNBC carries higher TMB than other breast cancer subtypes, and recent data suggest that high-TMB TNBC cases may derive particular benefit from ICB in combination with chemotherapy (GeparNuevo, IMpassion130) or even ICB alone (KEYNOTE-119, TAPUR). Given the recent approval of pembrolizumab and atezolizumab in combination with chemotherapy for PD-L1-positive, metastatic TNBC, standardizing TMB calculation methods and cut-off values is of critical importance to deploy this clinical biomarker.

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