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. 2021 Mar 2;12(5):394-400.
doi: 10.18632/oncotarget.27877.

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

Tess A O'Meara  1 , Sara M Tolaney  2
Affiliations

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

Tess A O'Meara et al. Oncotarget. .

Abstract

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.

Keywords: breast cancer; immunotherapy; tumor mutational burden.

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Conflict of interest statement

CONFLICTS OF INTEREST SMT reports institutional research funding from AstraZeneca, Lilly, Merck, Nektar, Novartis, Pfizer, Genentech/Roche, Immunomedics, Exelixis, Bristol-Myers Squibb, Eisai, Nanostring, Cyclacel, Odonate, Seattle Genetics; and advisor/consultant role for AstraZeneca, Lilly, Merck, Nektar, Novartis, Pfizer, Genentech/Roche, Gilead, Immunomedics, Bristol-Myers Squibb, Eisai, Nanostring, Puma, Sanofi, Celldex, Paxman, Odonate, Seattle Genetics, Silverback Therapeutics, G1 Therapeutics, AbbVie, Anthenex, OncoPep, Outcomes4Me, Kyowa Kirin Pharmaceuticals, Daiichi-Sankyo, Samsung Bioepsis Inc.

References

    1. Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, Diéras V, Hegg R, Im SA, Shaw Wright G, Henschel V, Molinero L, Chui SY, et al., and IMpassion130 Trial Investigators. Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N Engl J Med. 2018; 379:2108–21. 10.1056/NEJMoa1809615. - DOI - PubMed
    1. Cortes J, Cescon DW, Rugo HS, Nowecki Z, Im SA, Yusof MM, Gallardo C, Lipatov O, Barrios CH, Holgado E, Iwata H, Masuda N, Otero MT, et al., and KEYNOTE-355 Investigators. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020; 396:1817–28. 10.1016/S0140-6736(20)32531-9. - DOI - PubMed
    1. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012; 12:252–64. 10.1038/nrc3239. - DOI - PMC - PubMed
    1. Karnik T, Kimler BF, Fan F, Tawfik O. PD-L1 in breast cancer: comparative analysis of 3 different antibodies. Hum Pathol. 2018; 72:28–34. 10.1016/j.humpath.2017.08.010. - DOI - PubMed
    1. Downes MR, Slodkowska E, Katabi N, Jungbluth AA, Xu B. Inter- and intraobserver agreement of programmed death ligand 1 scoring in head and neck squamous cell carcinoma, urothelial carcinoma and breast carcinoma. Histopathology. 2020; 76:191–200. 10.1111/his.13946. - DOI - PMC - PubMed