John Libbey Eurotext

Innovations & Thérapeutiques en Oncologie


Estrogen receptor alpha (ESR1) gene mutations and hormone therapy resistance in luminal breast cancers: a 2022 update Volume 8, issue 4, July-August 2022


  • Figure 1.


Hôpital Saint-Louis, APHP, 1, avenue Claude Vellefaux, 75475 Paris Cedex 10, France
Tirés à part : M. Espié
Remerciements et autres mentions :
Financement : aucun.
Liens d’intérêts : les auteurs déclarent ne pas avoir de lien d’intérêt.

Luminal breast cancer (estrogen receptor-positive [ER+]) is the most frequent breast cancer. Drugs that block ER activation are currently the standard of care for ER+ breast cancer. However, resistance to these treatments remains a major problem, leading to recurrence and metastasis. Mutations in the ER gene (ESR1) are one of the drivers of resistance to treatment. These mutations frequently induce constitutive transcriptional activation of the ESR1 gene and reduced sensitivity to ER-blocking therapies. These mutations are particularly deleterious in metastatic breast cancer, as they are present in approximately a third of tumours at this stage. This review summarizes the characteristics and functional consequences of ESR1 gene mutations as well as the clinical data on primary and metastatic luminal breast cancers. Finally, therapeutic strategies to counteract resistance (new drugs and drug combinations) are described and discussed.