[New therapeutical strategies in metastatic hormone-dependent breast cancer]

Bull Cancer. 2015 Apr;102(4):367-80. doi: 10.1016/j.bulcan.2015.02.013. Epub 2015 Mar 21.
[Article in French]

Abstract

Hormone-dependent breast cancer is the first example of cancer treated by targeted therapy for more than 30 years. Blocking estrogen pathway was the first therapeutical strategy for this subtype of breast cancer, and remains the principle of current standard treatment. Despite the efficacy of drugs used in endocrine therapy, hormone resistance is a major problem for the management of patients with hormone-dependent breast cancer. In this review, we will discuss the development of strategies targeting the PI3K/Akt/mTOR pathway, CDK4/6 (Cyclin Dependent Kinase 4/6) and FGFR (Fibroblast Growth Factor Receptor) in hormone-dependent metastatic breast cancer (ER+). Recent results of clinical trials showed that combination of endocrine therapy with such pharmacological inhibitors is a promising strategy to overcome endocrine resistance. Mutated forms and isoforms of ERα have been recently discovered and its targeting could represent an therapeutic alternative. Future progress will focus on the identification of new compounds and combinations with other targeted therapies to improve the efficacy of such inhibitors in clinical practice.

Keywords: Breast cancer; Cancer du sein; Cellular cycle; Cible thérapeutique; Cycle cellulaire; Dépendance hormonale; ER; Facteur de croissance; Growth factor; Hormonal dependance; RE; Resistance; Résistance; Therapeutic target.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Aromatase Inhibitors / therapeutic use
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Cyclin-Dependent Kinase 4 / antagonists & inhibitors
  • Cyclin-Dependent Kinase 6 / antagonists & inhibitors
  • Drug Resistance, Neoplasm*
  • Elafin / antagonists & inhibitors
  • Estrogen Receptor Antagonists / therapeutic use
  • Female
  • Humans
  • Molecular Targeted Therapy / methods
  • Neoplasms, Hormone-Dependent / drug therapy*
  • Neoplasms, Hormone-Dependent / metabolism
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Receptors, Fibroblast Growth Factor / antagonists & inhibitors
  • Selective Estrogen Receptor Modulators / therapeutic use
  • Sirolimus / analogs & derivatives
  • Sirolimus / therapeutic use
  • TOR Serine-Threonine Kinases / antagonists & inhibitors

Substances

  • Antineoplastic Agents, Hormonal
  • Aromatase Inhibitors
  • Elafin
  • Estrogen Receptor Antagonists
  • PI3 protein, human
  • Receptors, Fibroblast Growth Factor
  • Selective Estrogen Receptor Modulators
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6
  • Sirolimus