V. Massard, A. Harlé, L. Uwer, J.-L. Merlin
Oncologie, Vol.21, No.1, pp. 29-32, 2019, DOI:10.3166/onco-2019-0027
Abstract Acquired endocrine resistance remains one of the
main obstacles in the treatment of estrogen receptor (ER)
positive, HER2 negative advanced breast cancer. Recently,
activating ESR1 gene mutations affecting the ligand-binding
domain have been identified as a key mechanism in aromatase
inhibitor (AI) resistance. These mutations can be detected on
histological samples or circulating tumour DNA, using PCRbased assays or next-generation sequencing. They induce a
constitutive activation of ER, leading to acquired resistance
to AI; tamoxifen, fulvestrant and targeted therapies against
mTOR or CDK4/6 retain their efficacy. The use of monitoring
ESR1 mutations in clinical practice is still to be defined.… More >
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