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Review
. 2022 Aug 8:12:866889.
doi: 10.3389/fonc.2022.866889. eCollection 2022.

Precision Breast Cancer Medicine: Early Stage Triple Negative Breast Cancer-A Review of Molecular Characterisation, Therapeutic Targets and Future Trends

Karen Pinilla  1   2   3 , Lynsey M Drewett  1   2 , Rebecca Lucey  1   2 , Jean E Abraham  1   2   3
Affiliations
Review

Precision Breast Cancer Medicine: Early Stage Triple Negative Breast Cancer-A Review of Molecular Characterisation, Therapeutic Targets and Future Trends

Karen Pinilla et al. Front Oncol. .

Abstract

Personalised approaches to the management of all solid tumours are increasing rapidly, along with wider accessibility for clinicians. Advances in tumour characterisation and targeted therapies have placed triple-negative breast cancers (TNBC) at the forefront of this approach. TNBC is a highly heterogeneous disease with various histopathological features and is driven by distinct molecular alterations. The ability to tailor individualised and effective treatments for each patient is of particular importance in this group due to the high risk of distant recurrence and death. The mainstay of treatment across all subtypes of TNBC has historically been cytotoxic chemotherapy, which is often associated with off-target tissue toxicity and drug resistance. Neoadjuvant chemotherapy is commonly used as it allows close monitoring of early treatment response and provides valuable prognostic information. Patients who achieve a complete pathological response after neoadjuvant chemotherapy are known to have significantly improved long-term outcomes. Conversely, poor responders face a higher risk of relapse and death. The identification of those subgroups that are more likely to benefit from breakthroughs in the personalised approach is a challenge of the current era where several targeted therapies are available. This review presents an overview of contemporary practice, and promising future trends in the management of early TNBC. Platinum chemotherapy, DNA damage response (DDR) inhibitors, immune checkpoint inhibitors, inhibitors of the PI3K-AKT-mTOR, and androgen receptor (AR) pathways are some of the increasingly studied therapies which will be reviewed. We will also discuss the growing evidence for less-developed agents and predictive biomarkers that are likely to contribute to the forthcoming advances in this field. Finally, we will propose a framework for the personalised management of TNBC based upon the integration of clinico-pathological and molecular features to ensure that long-term outcomes are optimised.

Keywords: Breast cancer; biomarkers; early disease; precision medicine; target; therapeutic; triple negative.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Current therapeutics strategies in early TNBC. (A). Treatment spectrum (B). Treatment modalities for escalation and de-escalation.
Figure 2
Figure 2
Biomarker landscape in TNBC.
Figure 3
Figure 3
Proposed framework for the personalised treatment of early. TNBC.
See this image and copyright information in PMC

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