Prognostic and predictive value of circulating ESR1 mutations in metastatic breast cancer patients (mBC) progressing under aromatase inhibitor (AI) treatment.

Augusto, Laetitia; Sarafan-Vasseur, Nasrin; Perdrix, A.; Beaussire, Ludivine; Delacour, Julien; Sefrioui, David; Calbrix, Céline; Picquenot, Jean‐Michel; Frébourg, Thierry; Jardin, Fabrice; Fiore, Frédéric Di; Clatot, Florian

doi:10.1200/jco.2016.34.15_suppl.511

Cited by 2 publications

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“…A French cohort evaluated 74 patients and also reported worse outcomes for ESR1-mutated patients irrespective of treatment with ET or chemotherapy. No particular benefit of chemotherapy versus tamoxifen or fulvestrant was seen ( 44 ).…”

Section: Predictive Biomarkermentioning

confidence: 99%

Clinical Implications of ESR1 Mutations in Hormone Receptor-Positive Advanced Breast Cancer

Reinert

Saad²,

Barrios

et al. 2017

Front. Oncol.

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Hormone receptor-positive breast cancer is the most frequent breast cancer subtype. Endocrine therapy (ET) targeting the estrogen receptor (ER) pathway represents the main initial therapeutic approach. The major strategies include estrogen deprivation and the use of selective estrogen modulators or degraders, which show efficacy in the management of metastatic and early-stage disease. However, clinical resistance associated with progression of disease remains a significant therapeutic challenge. Mutations of the ESR1 gene, which encodes the ER, have been increasingly recognized as an important mechanism of ET resistance, with a prevalence that ranges from 11 to 39%. The majority of these mutations are located within the ligand-binding domain and result in an estrogen-independent constitutive activation of the ER and, therefore, resistance to estrogen deprivation therapy such as aromatase inhibition. ESR1 mutations, most often detected from liquid biopsies, have been consistently associated with a worse outcome and are being currently evaluated as a potential biomarker to guide therapeutic decisions. At the same time, targeted therapy directed to ESR1-mutated clones is an appealing concept with preclinical and clinical work in progress.

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Section: Predictive Biomarkermentioning

confidence: 99%

Clinical Implications of ESR1 Mutations in Hormone Receptor-Positive Advanced Breast Cancer

Reinert

Saad²,

Barrios

et al. 2017

Front. Oncol.

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Implications of ESR1 Mutations in Hormone Receptor-Positive Breast Cancer

Reinert

Gonçalves

Bines

2018

Curr. Treat. Options in Oncol.

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Endocrine treatment resistance eventually develops during adjuvant and even more often during hormonal treatment for advanced breast cancer (ABC). An ESR1 gene mutation, which encodes for the estrogen receptor (ER) protein, is one of the potential mechanisms of therapy resistance. The ESR1 mutations result in conformational changes in the ER leading to subsequent estrogen-independent transcriptional activity. These mutations are found at a lower level in early stage when compared to metastatic BC, more often through selective pressure after aromatase inhibitor (AI) treatment. Recent studies have explored the role of ESR1 mutations as potential prognostic and predictive biomarkers and showed that ESR1 mutations are likely associated with a more aggressive disease. However, definitive associations with outcome in order to make a specific treatment recommendation are yet to be found. The development of targeted therapy directed to ESR1-mutated clones is an appealing concept, and preclinical and clinical works are in progress. ESR1 mutations represent an exciting field with a rapidly increasing number of recent publications that will likely advance the knowledge of treatment resistance mechanisms and pave the way into more individualized patient endocrine treatment.

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Prognostic and predictive value of circulating ESR1 mutations in metastatic breast cancer patients (mBC) progressing under aromatase inhibitor (AI) treatment.

Cited by 2 publications

References 0 publications

Clinical Implications of ESR1 Mutations in Hormone Receptor-Positive Advanced Breast Cancer

Clinical Implications of ESR1 Mutations in Hormone Receptor-Positive Advanced Breast Cancer

Implications of ESR1 Mutations in Hormone Receptor-Positive Breast Cancer

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