Emerging PARP inhibitors for treating breast cancer

ABSTRACT

Introduction: Some breast cancers harbor defects in DNA repair pathways, including BRCA1 and BRCA2 mutations, leading to a genomic instability. Compromised DNA-damage repair response is found in 11 to 42% of triple negative breast cancers, with a frequency varying according to family history and ethnicity. The oral PARP inhibitors are a promising strategy in breast cancer exploiting Homologous Deficient Recombination deficiency (HRD) by a synthetic lethal approach. Several PARP inhibitors have currently reached early phase trials with studies on going in the adjuvant, neoadjuvant and metastatic setting.

Area covered: Here, we review completed and ongoing trials with PARP inhibitors as well as their mechanisms of activity and acquired resistance.

Expert opinion: PARP inhibitors show promising results in breast cancer. However, several issues are raised including the identification of biomarkers to predict treatment response and strategies to counteract emerging resistance.

KEYWORDS:

• Breast cancer
• BRCA1/2
• BRCAness
• PARP inhibitors

Declaration of Interest

Pr Campone reports conflicts of interest with Astra Zeneca (Board member). Dr Frenel declares conflicts of interest with Pfizer, Roche, Astra Zeneca (Board member and travel fees). Dr Augereau declares conflicts of interest with Pfizer and Novartis. Dr Robert reports conflicts of interest with Amgen, Merck and Novartis (travel fees and honoraria).

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 study was not funded.