The evolving therapeutic landscape of antibody–drug conjugates in breast cancer

ABSTRACT

Introduction

Antibody–drug conjugates (ADCs) are a relatively new class of anti-cancer therapies approved for a number of malignancies, including breast cancer. Their unique structure, consisting of a monoclonal antibody connected via a linker to a toxic payload, combines characteristics of both targeted therapy and chemotherapy.

Areas covered

In this review, we discuss the unique molecular structure and pharmacologic principles of ADCs and present the clinical efficacy and relevant toxicities of ADCs both approved and in development. While HER2 is the most studied target with approved agents for both HER2-positive and HER2-low expressing tumors, novel targets in HER2-negative disease have expanded our therapeutic capabilities significantly.

Expert opinion

ADCs are a promising, novel drug class with significant efficacy in all breast cancer subtypes. They are generally safe and well-tolerated. However, further research is necessary to improve their therapeutic potential. The development of predictive biomarkers to identify patients with greatest benefit, improved understanding of drug resistance to advance combination therapies, and novel targets are needed to further the field.

KEYWORDS:

• Breast cancer
• antibody–drug conjugates
• HER2-low
• drug development
• clinical trials
• TROP2

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

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

Additional information

Funding

N Chen receives funding from the Lynn Sage Foundation. R Nanda receives funding from the Breast Cancer Research Foundation and the National Cancer Institute Specialized Programs of Research Excellence.