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ESR1 Gene Mutations and Liquid Biopsy in ER-Positive Breast Cancers: A Small Step Forward, a Giant Leap for Personalization of Endocrine Therapy?

SIMPLE SUMMARY: Endocrine therapy (ET) remains the mainstay of treatment for Hormone Receptor-positive breast cancer, both in the early and advanced settings. The acquisition of mutations in the ESR1 gene encoding the estrogen receptor represents one of the main resistance mechanisms to ET. A conven...

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Autores principales: Betz, Margaux, Massard, Vincent, Gilson, Pauline, Witz, Andréa, Dardare, Julie, Harlé, Alexandre, Merlin, Jean-Louis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10649433/
https://www.ncbi.nlm.nih.gov/pubmed/37958343
http://dx.doi.org/10.3390/cancers15215169
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author Betz, Margaux
Massard, Vincent
Gilson, Pauline
Witz, Andréa
Dardare, Julie
Harlé, Alexandre
Merlin, Jean-Louis
author_facet Betz, Margaux
Massard, Vincent
Gilson, Pauline
Witz, Andréa
Dardare, Julie
Harlé, Alexandre
Merlin, Jean-Louis
author_sort Betz, Margaux
collection PubMed
description SIMPLE SUMMARY: Endocrine therapy (ET) remains the mainstay of treatment for Hormone Receptor-positive breast cancer, both in the early and advanced settings. The acquisition of mutations in the ESR1 gene encoding the estrogen receptor represents one of the main resistance mechanisms to ET. A conventional tumor tissue biopsy can be used to detect ESR1 mutations; however, these mutations are less likely to present on initial tissue biopsy, and such an invasive approach is hardly repeatable over time for longitudinal disease monitoring. The research of ESR1 mutations in liquid biopsies based on the analysis of circulating cell-free DNA in plasma is of increasing interest and has been recently recommended to guide therapy in patients with estrogen receptor-positive breast cancers at progression under ET. This comprehensive review reports the most recent advances and recommendations in this field and compares the different techniques available for the analysis of the ESR1 gene in liquid biopsy. ABSTRACT: The predominant forms of breast cancer (BC) are hormone receptor-positive (HR+) tumors characterized by the expression of estrogen receptors (ERs) and/or progesterone receptors (PRs). Patients with HR+ tumors can benefit from endocrine therapy (ET). Three types of ET are approved for the treatment of HR+ BCs and include selective ER modulators, aromatase inhibitors, and selective ER downregulators. ET is the mainstay of adjuvant treatment in the early setting and the backbone of the first-line treatment in an advanced setting; however, the emergence of acquired resistance can lead to cancer recurrence or progression. The mechanisms of ET resistance are often related to the occurrence of mutations in the ESR1 gene, which encodes the ER-alpha protein. As ESR1 mutations are hardly detectable at diagnosis but are present in 30% to 40% of advanced BC (ABC) after treatment, the timeline of testing is crucial. To manage this resistance, ESR1 testing has recently been recommended; in ER+ HER2− ABC and circulating cell-free DNA, so-called liquid biopsy appears to be the most convenient way to detect the emergence of ESR1 mutations. Technically, several options exist, including Next Generation Sequencing and ultra-sensitive PCR-based techniques. In this context, personalization of ET through the surveillance of ESR1 mutations in the plasma of HR+ BC patients throughout the disease course represents an innovative way to improve the standard of care.
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spelling pubmed-106494332023-10-27 ESR1 Gene Mutations and Liquid Biopsy in ER-Positive Breast Cancers: A Small Step Forward, a Giant Leap for Personalization of Endocrine Therapy? Betz, Margaux Massard, Vincent Gilson, Pauline Witz, Andréa Dardare, Julie Harlé, Alexandre Merlin, Jean-Louis Cancers (Basel) Review SIMPLE SUMMARY: Endocrine therapy (ET) remains the mainstay of treatment for Hormone Receptor-positive breast cancer, both in the early and advanced settings. The acquisition of mutations in the ESR1 gene encoding the estrogen receptor represents one of the main resistance mechanisms to ET. A conventional tumor tissue biopsy can be used to detect ESR1 mutations; however, these mutations are less likely to present on initial tissue biopsy, and such an invasive approach is hardly repeatable over time for longitudinal disease monitoring. The research of ESR1 mutations in liquid biopsies based on the analysis of circulating cell-free DNA in plasma is of increasing interest and has been recently recommended to guide therapy in patients with estrogen receptor-positive breast cancers at progression under ET. This comprehensive review reports the most recent advances and recommendations in this field and compares the different techniques available for the analysis of the ESR1 gene in liquid biopsy. ABSTRACT: The predominant forms of breast cancer (BC) are hormone receptor-positive (HR+) tumors characterized by the expression of estrogen receptors (ERs) and/or progesterone receptors (PRs). Patients with HR+ tumors can benefit from endocrine therapy (ET). Three types of ET are approved for the treatment of HR+ BCs and include selective ER modulators, aromatase inhibitors, and selective ER downregulators. ET is the mainstay of adjuvant treatment in the early setting and the backbone of the first-line treatment in an advanced setting; however, the emergence of acquired resistance can lead to cancer recurrence or progression. The mechanisms of ET resistance are often related to the occurrence of mutations in the ESR1 gene, which encodes the ER-alpha protein. As ESR1 mutations are hardly detectable at diagnosis but are present in 30% to 40% of advanced BC (ABC) after treatment, the timeline of testing is crucial. To manage this resistance, ESR1 testing has recently been recommended; in ER+ HER2− ABC and circulating cell-free DNA, so-called liquid biopsy appears to be the most convenient way to detect the emergence of ESR1 mutations. Technically, several options exist, including Next Generation Sequencing and ultra-sensitive PCR-based techniques. In this context, personalization of ET through the surveillance of ESR1 mutations in the plasma of HR+ BC patients throughout the disease course represents an innovative way to improve the standard of care. MDPI 2023-10-27 /pmc/articles/PMC10649433/ /pubmed/37958343 http://dx.doi.org/10.3390/cancers15215169 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Betz, Margaux
Massard, Vincent
Gilson, Pauline
Witz, Andréa
Dardare, Julie
Harlé, Alexandre
Merlin, Jean-Louis
ESR1 Gene Mutations and Liquid Biopsy in ER-Positive Breast Cancers: A Small Step Forward, a Giant Leap for Personalization of Endocrine Therapy?
title ESR1 Gene Mutations and Liquid Biopsy in ER-Positive Breast Cancers: A Small Step Forward, a Giant Leap for Personalization of Endocrine Therapy?
title_full ESR1 Gene Mutations and Liquid Biopsy in ER-Positive Breast Cancers: A Small Step Forward, a Giant Leap for Personalization of Endocrine Therapy?
title_fullStr ESR1 Gene Mutations and Liquid Biopsy in ER-Positive Breast Cancers: A Small Step Forward, a Giant Leap for Personalization of Endocrine Therapy?
title_full_unstemmed ESR1 Gene Mutations and Liquid Biopsy in ER-Positive Breast Cancers: A Small Step Forward, a Giant Leap for Personalization of Endocrine Therapy?
title_short ESR1 Gene Mutations and Liquid Biopsy in ER-Positive Breast Cancers: A Small Step Forward, a Giant Leap for Personalization of Endocrine Therapy?
title_sort esr1 gene mutations and liquid biopsy in er-positive breast cancers: a small step forward, a giant leap for personalization of endocrine therapy?
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10649433/
https://www.ncbi.nlm.nih.gov/pubmed/37958343
http://dx.doi.org/10.3390/cancers15215169
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