Molecular profiling of aromatase inhibitor sensitive and resistant ER+HER2- postmenopausal breast cancers.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
07 07 2023
07 07 2023
Historique:
received:
14
06
2022
accepted:
15
06
2023
medline:
10
7
2023
pubmed:
8
7
2023
entrez:
7
7
2023
Statut:
epublish
Résumé
Aromatase inhibitors (AIs) reduce recurrences and mortality in postmenopausal patients with oestrogen receptor positive (ER+) breast cancer (BC), but >20% of patients will eventually relapse. Given the limited understanding of intrinsic resistance in these tumours, here we conduct a large-scale molecular analysis to identify features that impact on the response of ER + HER2- BC to AI. We compare the 15% of poorest responders (PRs, n = 177) as measured by proportional Ki67 changes after 2 weeks of neoadjuvant AI to good responders (GRs, n = 190) selected from the top 50% responders in the POETIC trial and matched for baseline Ki67 categories. In this work, low ESR1 levels are associated with poor response, high proliferation, high expression of growth factor pathways and non-luminal subtypes. PRs having high ESR1 expression have similar proportions of luminal subtypes to GRs but lower plasma estradiol levels, lower expression of estrogen response genes, higher levels of tumor infiltrating lymphocytes and immune markers, and more TP53 mutations.
Identifiants
pubmed: 37419892
doi: 10.1038/s41467-023-39613-z
pii: 10.1038/s41467-023-39613-z
pmc: PMC10328947
doi:
Substances chimiques
Aromatase Inhibitors
0
Ki-67 Antigen
0
Receptors, Estrogen
0
Receptor, ErbB-2
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4017Informations de copyright
© 2023. The Author(s).
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