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Primary endocrine resistance of ER+ breast cancer with ESR1 mutations interrogated by droplet digital PCR

We investigated the patterns of recurrence and primary endocrine resistance according to estrogen receptor (ER) alpha gene (ESR1) mutations, as assessed by digital droplet (dd) PCR, in patients with non-metastatic ER+ breast cancer. We collected 121 formalin-fixed paraffin-embedded (FFPE) surgical s...

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Autores principales: Ahn, Sung Gwe, Bae, Soong June, Kim, Yoonjung, Ji, Jung Hwan, Chu, Chihhao, Kim, Dooreh, Lee, Janghee, Cha, Yoon Jin, Lee, Kyung-A, Jeong, Joon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9061813/
https://www.ncbi.nlm.nih.gov/pubmed/35501333
http://dx.doi.org/10.1038/s41523-022-00424-y
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author Ahn, Sung Gwe
Bae, Soong June
Kim, Yoonjung
Ji, Jung Hwan
Chu, Chihhao
Kim, Dooreh
Lee, Janghee
Cha, Yoon Jin
Lee, Kyung-A
Jeong, Joon
author_facet Ahn, Sung Gwe
Bae, Soong June
Kim, Yoonjung
Ji, Jung Hwan
Chu, Chihhao
Kim, Dooreh
Lee, Janghee
Cha, Yoon Jin
Lee, Kyung-A
Jeong, Joon
author_sort Ahn, Sung Gwe
collection PubMed
description We investigated the patterns of recurrence and primary endocrine resistance according to estrogen receptor (ER) alpha gene (ESR1) mutations, as assessed by digital droplet (dd) PCR, in patients with non-metastatic ER+ breast cancer. We collected 121 formalin-fixed paraffin-embedded (FFPE) surgical specimens from ER+ breast cancer patients who had relapsed after surgery. Genomic DNA was extracted from the FFPE samples and ESR1 mutations were evaluated using ddPCR. ESR1 mutations were detected in 9 (7.4%) of 121 primary breast cancer specimens. The median recurrence-free interval and overall survival were significantly lower in patients with ESR1 mutations than in those without. Of the patients treated with ET (N = 98), eight had ESR1 mutations. Of these, six (75.0%) had primary endocrine resistance and two (25.0%) had secondary endocrine resistance. By contrast, only 22 of 90 (24.4%) patients without ESR1 mutations had primary endocrine resistance. A multivariable model showed that an ESR1 mutation is a significant risk factor for primary endocrine resistance. Our findings provide clinical evidence that the presence of rare ESR1 mutant clones identified by ddPCR in primary tumors is associated with primary endocrine resistance in an adjuvant setting.
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spelling pubmed-90618132022-05-04 Primary endocrine resistance of ER+ breast cancer with ESR1 mutations interrogated by droplet digital PCR Ahn, Sung Gwe Bae, Soong June Kim, Yoonjung Ji, Jung Hwan Chu, Chihhao Kim, Dooreh Lee, Janghee Cha, Yoon Jin Lee, Kyung-A Jeong, Joon NPJ Breast Cancer Article We investigated the patterns of recurrence and primary endocrine resistance according to estrogen receptor (ER) alpha gene (ESR1) mutations, as assessed by digital droplet (dd) PCR, in patients with non-metastatic ER+ breast cancer. We collected 121 formalin-fixed paraffin-embedded (FFPE) surgical specimens from ER+ breast cancer patients who had relapsed after surgery. Genomic DNA was extracted from the FFPE samples and ESR1 mutations were evaluated using ddPCR. ESR1 mutations were detected in 9 (7.4%) of 121 primary breast cancer specimens. The median recurrence-free interval and overall survival were significantly lower in patients with ESR1 mutations than in those without. Of the patients treated with ET (N = 98), eight had ESR1 mutations. Of these, six (75.0%) had primary endocrine resistance and two (25.0%) had secondary endocrine resistance. By contrast, only 22 of 90 (24.4%) patients without ESR1 mutations had primary endocrine resistance. A multivariable model showed that an ESR1 mutation is a significant risk factor for primary endocrine resistance. Our findings provide clinical evidence that the presence of rare ESR1 mutant clones identified by ddPCR in primary tumors is associated with primary endocrine resistance in an adjuvant setting. Nature Publishing Group UK 2022-05-02 /pmc/articles/PMC9061813/ /pubmed/35501333 http://dx.doi.org/10.1038/s41523-022-00424-y Text en © The Author(s) 2022, corrected publication 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Ahn, Sung Gwe
Bae, Soong June
Kim, Yoonjung
Ji, Jung Hwan
Chu, Chihhao
Kim, Dooreh
Lee, Janghee
Cha, Yoon Jin
Lee, Kyung-A
Jeong, Joon
Primary endocrine resistance of ER+ breast cancer with ESR1 mutations interrogated by droplet digital PCR
title Primary endocrine resistance of ER+ breast cancer with ESR1 mutations interrogated by droplet digital PCR
title_full Primary endocrine resistance of ER+ breast cancer with ESR1 mutations interrogated by droplet digital PCR
title_fullStr Primary endocrine resistance of ER+ breast cancer with ESR1 mutations interrogated by droplet digital PCR
title_full_unstemmed Primary endocrine resistance of ER+ breast cancer with ESR1 mutations interrogated by droplet digital PCR
title_short Primary endocrine resistance of ER+ breast cancer with ESR1 mutations interrogated by droplet digital PCR
title_sort primary endocrine resistance of er+ breast cancer with esr1 mutations interrogated by droplet digital pcr
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9061813/
https://www.ncbi.nlm.nih.gov/pubmed/35501333
http://dx.doi.org/10.1038/s41523-022-00424-y
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