Advances in the treatment of advanced oestrogen-receptor-positive breast cancer

Lancet. 2017 Jun 17;389(10087):2403-2414. doi: 10.1016/S0140-6736(16)32419-9. Epub 2016 Dec 7.

Abstract

Oestrogen-receptor-positive breast cancer is the most common subtype of breast cancer. Endocrine therapies that target the dependence of this subtype on the oestrogen receptor have substantial activity, yet the development of resistance to therapy is inevitable in advanced cancer. Major progress has been made in identifying the drivers of oestrogen-receptor-positive breast cancer and the mechanisms of resistance to endocrine therapy. This progress has translated into major advances in the treatment of advanced breast cancer, with several targeted therapies that enhance the efficacy of endocrine therapy; inhibitors of mTOR and inhibitors of the cyclin-dependent kinases CDK4 and CDK6 substantially improve progression-free survival. A new wave of targeted therapies is being developed, including inhibitors of PI3K, AKT, and HER2, and a new generation of oestrogen-receptor degraders. Considerable challenges remain in patient selection, deciding on the most appropriate order in which to administer therapies, and establishing whether cross-resistance occurs between therapies.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Aromatase Inhibitors / therapeutic use
  • Breast Neoplasms / chemistry*
  • Breast Neoplasms / drug therapy*
  • Cyclin-Dependent Kinase 4 / antagonists & inhibitors
  • Cyclin-Dependent Kinase 6 / antagonists & inhibitors
  • Female
  • Humans
  • Molecular Targeted Therapy / methods*
  • Nuclear Proteins / antagonists & inhibitors
  • Piperazines / therapeutic use
  • Pyridines / therapeutic use
  • Receptors, Estrogen / analysis*
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • Transcription Factors / antagonists & inhibitors

Substances

  • Antineoplastic Agents
  • Aromatase Inhibitors
  • Nuclear Proteins
  • PI3KCA protein, human
  • Piperazines
  • Pyridines
  • Receptors, Estrogen
  • Transcription Factors
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • CDK4 protein, human
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6
  • palbociclib