Biologic therapy for advanced breast cancer: recent advances and future directions

ABSTRACT

Introduction

Advanced breast cancer (ABC) is a leading cause of mortality, morbidity, and disability in women worldwide. For decades, treatment of ABC has relied on chemotherapy and endocrine treatments (ET), until HER2 was recognized as a ‘druggable’ target in the 1990s. Thereafter, various anti-HER2 drugs have been approved for the HER2-positive subtype, but only in the last few years, biologic agents targeting different pathways have entered the therapeutic arsenal of luminal and triple-negative cancers.

Areas covered

The purpose of the present review is to recapitulate the most promising novel biologic agents being developed for the treatment of ABC. New drugs for all breast cancer subtypes are discussed, as well as some potential future directions in ABC treatment.

Expert opinion

Several biologic drugs have been recently approved, revolutionizing ABC treatment algorithms: key examples are CDK4/6-inhibitors and the PI3K-inhibitor alpelisib for endocrine-positive ABC; atezolizumab for triple-negative cancers; two PARP-inhibitors for HER2-negative germinal BRCA-mutated cancers. Additionally, multiple drugs are demonstrating activity in late-phase clinical trials for all subtypes. While some of these represent pharmacological evolutions of previously approved drugs, some others might pave the way for new paradigms in ABC, challenging both its classification and current treatment algorithms.

KEYWORDS:

• Antibody-drug conjugates
• breast cancer
• CDK4/6 inhibitors
• HER2-low
• immunotherapy
• new drugs
• PARP inhibitors
• precision medicine

Article highlights

• In the last 20 years, the introduction of biologic drugs has progressively revolutionized treatment algorithms of all breast cancer subtypes

• More recently, an accelerated pace in biologic drug approval in breast cancer has been observed, with about half of all approvals taking place in the last 3 years

• Novel anti-HER2 antibody-drug conjugates are challenging traditional treatment paradigms, showing activity in the emerging entity of HER2-low breast cancers

• As more genetic alterations become actionable, molecular profiling of ABC becomes increasingly important for the optimal selection of treatments

• Biologic treatments inevitably increase treatment costs, and a major challenge in the future will be ensuring optimal accessibility to novel treatments in developing countries

This box summarizes key points contained in the article.

Acknowledgments

We thank Dario Trapani for supporting proofreading.

Declaration of interest

G Curigliano received honoraria for speaker, consultancy or advisory rule from Roche, Pfizer, Novartis, Seattle Genetics, Lilly, Ellipses Pharma, Foundation Medicine, and Samsung. 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 relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper is not funded.