The landscape of systemic therapy for early stage triple-negative breast cancer

ABSTRACT

Introduction

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with higher risk of disease recurrence and mortality than other breast cancer subtypes. Historically, chemotherapy has been the primary systemic treatment for early stage TNBC. Recent developments in immune checkpoint inhibitors (ICIs) and novel therapeutic agents have transformed the treatment of TNBC.

Areas covered

This review provides a comprehensive overview of the current evidence on treatment of early stage TNBC. We highlight the incorporation of ICIs and other targeted therapies in (neo)adjuvant treatment and the ongoing development of novel therapeutic agents.

Expert opinion

The landscape of early TNBC treatment is rapidly evolving, which has given rise to the introduction of ICIs and PARP inhibitors into the systemic therapy. Despite modest improvement in the pathologic complete response (pCR) rate, ICI plus chemotherapy significantly improves long-term outcomes and is now used in (neo)adjuvant treatment of patients with TNBC and high risk for disease recurrence. Capecitabine remains the standard adjuvant treatment for residual disease, with olaparib being an option for patients with germline BRCA1/2 mutations. Early detection of minimal residual disease may identify patients requiring additional therapy to prevent recurrence.

KEYWORDS:

• Triple-negative breast cancer
• systemic adjuvant therapy
• immune checkpoint inhibitor
• targeted therapy
• chemotherapy
• pathologic complete response

Article highlights

• Adjuvant systemic chemotherapy remains standard for patients with early stage TNBC with tumor > 1 cm. The neoadjuvant approach is preferred if tumor > 2 cm and/or node-positive.

• Addition of carboplatin to neoadjuvant chemotherapy (NACT) can be considered based on risk/benefit evaluation, given the improvement of the pCR rate and event-free survival in patients with stage II-III TNBC.

• For patients with residual cancer after NACT, adjuvant capecitabine is the standard of care. For those with germline BRCA1/2 mutation, adjuvant olaparib is an option.

• Pembrolizumab is approved in combination with NACT and followed as a single-agent adjuvant treatment for high-risk stage II-III TNBC.

• The landscape of TNBC treatment is rapidly evolving, with new immune checkpoint inhibitors and antibody-drug conjugates expected to be included in future treatment.

This box summarizes key points contained in the article.

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 of this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was supported by The Einstein Paul Calabresi Career Development Program [NIH 5K12CA132783-08] and NIH/National Center for Advancing Translational Science (NCATS) Einstein-Montefiore CTSA [Grant Number UL1TR001073].