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

Expert Opin Pharmacother. 2020 Apr;21(6):687-699. doi: 10.1080/14656566.2020.1724957. Epub 2020 Feb 13.

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; HRD score; PARP-inhibitors; PD-1/PD-L1 inhibitors; chemotherapy; immunotherapy; platinum agents; triple-negative breast cancer.

Publication types

  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor*
  • Carboplatin / therapeutic use*
  • Cell Cycle Checkpoints / drug effects*
  • Cell Cycle Checkpoints / immunology
  • DNA Repair
  • Female
  • Humans
  • Molecular Targeted Therapy
  • Neoadjuvant Therapy / methods*
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use*
  • Precision Medicine
  • Predictive Value of Tests
  • Triple Negative Breast Neoplasms / drug therapy*

Substances

  • Biomarkers, Tumor
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Carboplatin