‘Why is survival with triple negative breast cancer so low? insights and talking points from preclinical and clinical research’

ABSTRACT

Introduction

Triple negative breast cancer is typically related to poor prognosis, early metastasis, and high recurrence rate. Intrinsic and extrinsic biological features of TNBC and resistance mechanisms to conventional therapies can support its aggressive behavior, characterizing TNBC how extremely heterogeneous. Novel combination strategies are under investigation, including immunotherapeutic agents, anti-drug conjugates, PARP inhibitors, and various targeting agents, exploring, in the meanwhile, possible predictive biomarkers to correctly select patients for the optimal treatment for their specific subtype.

Areas covered

This article examines the main malignity characteristics across different subtype, both histological and molecular, and the resistance mechanisms, both primary and acquired, to different drugs explored in the landscape of TNBC treatment, that lead TNBC to still has high mortality rate.

Expert opinion

The complexity of TNBC is not only the main reason of its aggressivity, but its heterogeneity should be exploited in terms of therapeutics opportunities, combining agents with different mechanism of action, after a correct selection by biologic or molecular biomarkers. The main goal is to understand what TNBC really is and to act selectively on its characteristics, with a personalized anticancer treatment.

KEYWORDS:

• Triple negative breast cancer
• resistance mechanisms
• predictive biomarkers
• novel drug combinations
• target therapy
• immunotherapy

Article highlights

• Triple negative breast cancer is typically related to poor prognosis, early metastasis, and high recurrence rate.

• TNBC is characterized by extremely heterogeneity and several classifications of different subtypes have been made.

• TNBC has an extreme ability to develop resistance mechanisms to different agents explored in various setting of treatment.

• The absence of known targetable receptors led to the lack of a single effective therapeutic option and chemotherapy has been the standard of care for a long time.

• Combination strategy of chemotherapy with new category drugs, such as ADCs, PARP-i, or immunotherapy agents, should rise the bar of the pathological response, clinical benefit, and survival in TNBC.

Declaration of interest

G Curigliano declares fees form advisory board for Roche, BMS, Novartis, Lilly, Pfizer, Seagen, Ellipsis, Gilead, Merck, Celcuity. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.