Targeted and immuno-biology driven treatment strategies for triple-negative breast cancer: current knowledge and future perspectives

ABSTRACT

Introduction: Accounting for about 15% of breast cancer patients, triple-negative breast cancer (TNBC) is responsible for 25% of disease related deaths, more frequent distant spread and visceral metastasis. However, improving survival in TNBC failed and primary resistance, immunological ignorance and tumor heterogeneity limit clinical activity of novel therapies. In view of recent molecular, genetic and immunologic insights, this review aims to describe the current status of immunological and targeted treatments from a hypothesis driven perspective.

Areas covered: Recent preclinical studies and ongoing clinical trials for immune directed and targeted treatments of TNBC are summarized, including immune-checkpoint blockade, resistance mechanisms, inhibition of poly (ADP-ribose) polymerase (PARP), combinatorial strategies as well as preclinical, hypothesis generating studies.

Expert commentary: Sustained responses have been observed with immune-checkpoint blockade and PARP inhibitors demonstrated remarkable efficacy in germline BRCA mutated TNBC. In order to generate clinical success of many other, to date ineffective, targeted and immune therapies, the integration of multidimensional, large amounts of data, will be essential and likely accelerate treatment progress of TNBC.

KEYWORDS:

• Triple-negative breast cancer
• immune checkpoint blockade
• targeted therapy
• BRCA
• PARP
• pembrolizumab
• PD-1
• PD-L1
• resistance

Declaration of interest

A Schneeweiss has received honoraria from Roche, Celgene, Pfizer, AstraZeneca, Novartis, and Bristol-Myers Squibb. C Fremd has received honoraria from Roche and Celgene. 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

A reviewer on this manuscript has disclosed that they serve on the advisory board for Immunomedics who developed sacituzumab. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript has not been funded.