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Emerging strategies for TNBC with early clinical data: new chemoimmunotherapy strategies

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Abstract

Purpose

The use of immune checkpoint inhibitors in combination with chemotherapy for the treatment of triple-negative breast cancer is becoming more widespread as efficacy data accumulates. However, outcomes remain less than optimal and not all patients benefit from treatment. The aim of this article is to review the emerging chemoimmunotherapy strategies for triple-negative breast cancer.

Methods

Searches were undertaken on Pubmed and Clinicaltrials.gov for relevant publications and trials.

Results

Preclinical and clinical data have provided insights into the differing immunomodulatory effects of chemotherapy agents, highlighting the immunostimulatory properties of anthracyclines. Mechanisms of resistance to immune checkpoint inhibition are discussed and the potential role of phosphatidylinositol 3-kinase (PI3K)/AKT and MAPK/ERK kinase (MEK) inhibitors in overcoming resistance. Finally, the emerging therapeutic class of antibody–drug conjugates for triple-negative breast cancer in combination with immune checkpoint inhibitors is reviewed.

Conclusions

The type and sequence of chemotherapy agents play an important role in optimising the response to immune checkpoint inhibitors. Antibody–drug conjugates in combination with immune checkpoint inhibitors are a promising area of development.

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Data availability

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Code availability

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Abbreviations

ADC:

Antibody–drug conjugate

CI:

Confidence interval

CSF-1R:

Colony stimulating factor-1 receptor

DC:

Dendritic cell

DFI:

Disease free interval

DFS:

Disease free survival

FDA:

Food and Drug Administration

HR:

Hazard ratio

ICI:

Immune checkpoint inhibitor

IFNγ:

Interferon γ

ITT:

Intention to treat

MAPK:

Mitogen activated protein kinase

MDSC:

Myeloid-derived suppressor cells

MEK:

MAPK/ERK kinase

MHC:

Major histocompatibility complex

NK:

Natural killer cell

ORR:

Objective response rate

OR:

Odds ratio

OS:

Overall survival

PARP:

Poly-ADP ribose polymerase

pCR:

Pathological complete response

PD-1:

Programmed death 1

PD-L1:

Programmed death ligand 1

PFS:

Progression free survival

PI3K:

Phosphatidylinositol 3-kinase

TAM:

Tumour associated macrophage

TIL:

Tumour infiltrating lymphocyte

TGFβ:

Transforming growth factor β

TMB:

Tumour mutational burden

TME:

Tumour microenvironment

TNBC:

Triple-negative breast cancer

VEGF:

Vascular endothelial growth factor

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  1. Department of Medical Oncology, St Bartholomew’s Hospital, King George V Building, West Smithfield, London, EC1A 7BE, UK

    Peter E. Hall & Peter Schmid

  2. Barts Cancer Institute, Queen Mary University of London, London, UK

    Peter Schmid

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This was an invited review. The literature search and initial draft manuscript were done by PEH. PS critically revised the manuscript.

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PEH has received honoraria from Pfizer, Eisai, MSD and conference expenses from Lilly. PS has received honoraria from AstraZeneca, Pfizer, Novartis, Roche; has a consulting or advisory role with Genentech/Roche, AstraZeneca, Merck, Boehringer Ingelheim, Bayer, Pfizer, Novartis, Eisai, Celgene, Puma Biotechnology; has received institutional research funding from AstraZeneca, Astellas Pharma, Medivation, Oncogenex, Genentech, Novartis, Roche, Merck; has an immediate family member employed by Roche.

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Hall, P.E., Schmid, P. Emerging strategies for TNBC with early clinical data: new chemoimmunotherapy strategies. Breast Cancer Res Treat 193, 21–35 (2022). https://doi.org/10.1007/s10549-022-06547-x

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