Current trends in the treatment of HR+/HER2+ breast cancer

Future Oncol. 2021 May;17(13):1665-1681. doi: 10.2217/fon-2020-0504. Epub 2021 Mar 17.

Abstract

Treatment for HR+/HER2+ patients has been debated, as some tumors within this luminal HER2+ subtype behave like luminal A cancers, whereas others behave like non-luminal HER2+ breast cancers. Recent research and clinical trials have revealed that a combination of hormone and targeted anti-HER2 approaches without chemotherapy provides long-term disease control for at least some HR+/HER2+ patients. Novel anti-HER2 therapies, including neratinib and trastuzumab emtansine, and new agents that are effective in HR+ cancers, including the next generation of oral selective estrogen receptor downregulators/degraders and CDK4/6 inhibitors such as palbociclib, are now being evaluated in combination. This review discusses current trials and results from previous studies that will provide the basis for current recommendations on how to treat newly diagnosed patients with HR+/HER2+ disease.

Keywords: HER2+; HR+/HER2+; breast cancer; clinical trials; combination treatment; emerging therapeutics; luminal HER2; triple-positive breast cancer.

Publication types

  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast / pathology
  • Breast / surgery
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Camptothecin / analogs & derivatives
  • Camptothecin / pharmacology
  • Camptothecin / therapeutic use
  • Chemotherapy, Adjuvant / methods
  • Chemotherapy, Adjuvant / trends
  • Clinical Trials as Topic
  • Estrogen Receptor Antagonists / pharmacology
  • Estrogen Receptor Antagonists / therapeutic use
  • Female
  • Humans
  • Immunoconjugates / pharmacology
  • Immunoconjugates / therapeutic use
  • Mastectomy*
  • Molecular Targeted Therapy / methods
  • Molecular Targeted Therapy / trends
  • Neoadjuvant Therapy / methods
  • Neoadjuvant Therapy / trends*
  • Piperazines / pharmacology
  • Piperazines / therapeutic use
  • Progression-Free Survival
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Pyridines / pharmacology
  • Pyridines / therapeutic use
  • Quinolines / pharmacology
  • Quinolines / therapeutic use
  • Receptor, ErbB-2 / analysis
  • Receptor, ErbB-2 / antagonists & inhibitors
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / analysis
  • Receptors, Estrogen / antagonists & inhibitors
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / analysis
  • Receptors, Progesterone / metabolism
  • Trastuzumab / pharmacology
  • Trastuzumab / therapeutic use

Substances

  • Estrogen Receptor Antagonists
  • Immunoconjugates
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyridines
  • Quinolines
  • Receptors, Estrogen
  • Receptors, Progesterone
  • trastuzumab deruxtecan
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • palbociclib
  • neratinib
  • Trastuzumab
  • Camptothecin