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Unusual phylogenetic tree and circulating actionable ESR1 mutations in an aggressive luminal/HER2-low breast cancer: Case report

Under therapeutic pressure aggressive tumors evolve rapidly. Herein, a luminal B/HER2-low breast cancer was tracked for >3 years during a total of 6 largely unsuccessful therapy lines, from adjuvant to advanced settings. Targeted next generation sequencing (NGS) of the primary lesion, two metasta...

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Autores principales: Allegretti, Matteo, Barberi, Vittoria, Ercolani, Cristiana, Vidiri, Antonello, Giordani, Elena, Ciliberto, Gennaro, Giacomini, Patrizio, Fabi, Alessandra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9874630/
https://www.ncbi.nlm.nih.gov/pubmed/36713585
http://dx.doi.org/10.3389/fonc.2022.1050452
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author Allegretti, Matteo
Barberi, Vittoria
Ercolani, Cristiana
Vidiri, Antonello
Giordani, Elena
Ciliberto, Gennaro
Giacomini, Patrizio
Fabi, Alessandra
author_facet Allegretti, Matteo
Barberi, Vittoria
Ercolani, Cristiana
Vidiri, Antonello
Giordani, Elena
Ciliberto, Gennaro
Giacomini, Patrizio
Fabi, Alessandra
author_sort Allegretti, Matteo
collection PubMed
description Under therapeutic pressure aggressive tumors evolve rapidly. Herein, a luminal B/HER2-low breast cancer was tracked for >3 years during a total of 6 largely unsuccessful therapy lines, from adjuvant to advanced settings. Targeted next generation sequencing (NGS) of the primary lesion, two metastases and 14 blood drawings suggested a striking, unprecedented coexistence of three evolution modes: punctuated, branched and convergent. Punctuated evolution of the trunk was supported by en bloc inheritance of a large set (19 distinct genes) of copy number alterations. Branched evolution was supported by the distribution of site-specific SNVs. Convergent evolution was characterized by a unique asynchronous expansion of three actionable (OncoKB level 3A) mutations at two consecutive ESR1 codons. Low or undetectable in all the sampled tumor tissues, ESR1 mutations expanded rapidly in blood during HER2/hormone double-blockade, and predicted life-threatening local progression at lung and liver metastatic foci. Dramatic clinical response to Fulvestrant (assigned off-label exclusively based on liquid biopsy) was associated with clearance of all 3 subclones and was in stark contrast to the poor therapeutic efficacy reported in large liquid biopsy-informed interventional trials. Altogether, deconvolution of the tumor phylogenetic tree, as shown herein, may help to customize treatment in breast cancers that rapidly develop refractoriness to multiple drugs.
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spelling pubmed-98746302023-01-26 Unusual phylogenetic tree and circulating actionable ESR1 mutations in an aggressive luminal/HER2-low breast cancer: Case report Allegretti, Matteo Barberi, Vittoria Ercolani, Cristiana Vidiri, Antonello Giordani, Elena Ciliberto, Gennaro Giacomini, Patrizio Fabi, Alessandra Front Oncol Oncology Under therapeutic pressure aggressive tumors evolve rapidly. Herein, a luminal B/HER2-low breast cancer was tracked for >3 years during a total of 6 largely unsuccessful therapy lines, from adjuvant to advanced settings. Targeted next generation sequencing (NGS) of the primary lesion, two metastases and 14 blood drawings suggested a striking, unprecedented coexistence of three evolution modes: punctuated, branched and convergent. Punctuated evolution of the trunk was supported by en bloc inheritance of a large set (19 distinct genes) of copy number alterations. Branched evolution was supported by the distribution of site-specific SNVs. Convergent evolution was characterized by a unique asynchronous expansion of three actionable (OncoKB level 3A) mutations at two consecutive ESR1 codons. Low or undetectable in all the sampled tumor tissues, ESR1 mutations expanded rapidly in blood during HER2/hormone double-blockade, and predicted life-threatening local progression at lung and liver metastatic foci. Dramatic clinical response to Fulvestrant (assigned off-label exclusively based on liquid biopsy) was associated with clearance of all 3 subclones and was in stark contrast to the poor therapeutic efficacy reported in large liquid biopsy-informed interventional trials. Altogether, deconvolution of the tumor phylogenetic tree, as shown herein, may help to customize treatment in breast cancers that rapidly develop refractoriness to multiple drugs. Frontiers Media S.A. 2023-01-11 /pmc/articles/PMC9874630/ /pubmed/36713585 http://dx.doi.org/10.3389/fonc.2022.1050452 Text en Copyright © 2023 Allegretti, Barberi, Ercolani, Vidiri, Giordani, Ciliberto, Giacomini and Fabi https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Allegretti, Matteo
Barberi, Vittoria
Ercolani, Cristiana
Vidiri, Antonello
Giordani, Elena
Ciliberto, Gennaro
Giacomini, Patrizio
Fabi, Alessandra
Unusual phylogenetic tree and circulating actionable ESR1 mutations in an aggressive luminal/HER2-low breast cancer: Case report
title Unusual phylogenetic tree and circulating actionable ESR1 mutations in an aggressive luminal/HER2-low breast cancer: Case report
title_full Unusual phylogenetic tree and circulating actionable ESR1 mutations in an aggressive luminal/HER2-low breast cancer: Case report
title_fullStr Unusual phylogenetic tree and circulating actionable ESR1 mutations in an aggressive luminal/HER2-low breast cancer: Case report
title_full_unstemmed Unusual phylogenetic tree and circulating actionable ESR1 mutations in an aggressive luminal/HER2-low breast cancer: Case report
title_short Unusual phylogenetic tree and circulating actionable ESR1 mutations in an aggressive luminal/HER2-low breast cancer: Case report
title_sort unusual phylogenetic tree and circulating actionable esr1 mutations in an aggressive luminal/her2-low breast cancer: case report
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9874630/
https://www.ncbi.nlm.nih.gov/pubmed/36713585
http://dx.doi.org/10.3389/fonc.2022.1050452
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