Neoadjuvant therapy for triple-negative breast cancer: potential predictive biomarkers of activity and efficacy of platinum chemotherapy, PARP- and immune-checkpoint-inhibitors

ABSTRACT

Introduction

Despite recent advances in the molecular characterization of triple-negative breast cancer (TNBC), the standard treatment for early-stage TNBC is represented by the historically used anthracycline and taxane-based chemotherapy. In this modern era of precision medicine, several new therapeutic strategies and novel agents have been investigated in the neoadjuvant setting of TNBC, in order to individualize treatment.

Areas covered

This review provides a comprehensive overview of the currently available evidence regarding the activity and efficacy of platinum agents, PARP- and immune-checkpoint-inhibitors for the neoadjuvant treatment of TNBC, highlighting the available data on potential predictive biomarkers of response or resistance to such treatments.

Expert opinion

The genomic and immune landscape of TNBC has encouraged the exploration of drugs that interfere with the DNA repair mechanism and that modulate immune response. Overall, these drugs seem to improve the pCR rate in TNBC, despite preliminary and heterogeneous results. Taking into account the economic issues and the side effects of these drugs, it is crucial to further explore the potential predictive role of BRCA mutational status and homologous recombination deficiency score, for platinum agents and PARP-inhibitors, and tumor infiltrating lymphocytes and other immune biomarkers for checkpoint inhibitors, respectively.

KEYWORDS:

• BRCA status
• chemotherapy
• HRD score
• immunotherapy
• PARP-inhibitors
• PD-1/PD-L1 inhibitors
• platinum agents
• triple-negative breast cancer

Article Highlights

• Although early-stage TNBCs continue to be treated as a single disease, genomic and transcriptomic analyses highlight a marked heterogeneity of this subtype.

• Several studies explored new therapeutic strategy and targeted agents, including platinum agents, PARP inhibitors and immune checkpoint inhibitors, in the neoadjuvant treatment of TNBC.

• A significant increase in the pCR rate from the addition of carboplatin and immune checkpoint inhibitors to standard chemotherapy seems consistent.

• The addition of PARP-inhibitors to platinum chemotherapy does not appear to further increase pCR rate.

• BRCA mutational status, HRD score and immune component of the tumor ecosystem have been explored as potential predictive biomarkers.

This box summarizes key points contained in the article.

Declaration of interest

E Bria has received honoraria or speaker’s fees from Merck Sharp and Dohme, AstraZeneca, Celgene, Pfizer Inc, Helsinn, Eli Lilly and Company, Bristol-Myers Squibb, Novartis and Roche. 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 or other relationships to disclose.

Additional information

Funding

This manuscript is not funded.