Impact of Duration of Neoadjuvant Aromatase Inhibitors on Molecular Expression Profiles in Estrogen Receptor-positive Breast Cancers.
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
15 03 2022
15 03 2022
Historique:
received:
26
07
2021
revised:
18
10
2021
accepted:
16
12
2021
pubmed:
31
12
2021
medline:
16
4
2022
entrez:
30
12
2021
Statut:
ppublish
Résumé
Aromatase inhibitor (AI) treatment is the standard of care for postmenopausal women with primary estrogen receptor-positive breast cancer. The impact of duration of neoadjuvant endocrine therapy (NET) on molecular characteristics is still unknown. We evaluated and compared changes of gene expression profiles under short-term (2-week) versus longer-term neoadjuvant AIs. Global gene expression profiles from the PeriOperative Endocrine Therapy for Individualised Care (POETIC) trial (137 received 2 weeks of AIs and 47 received no treatment) and targeted gene expression from 80 patients with breast cancer treated with NET for more than 1 month (NeoAI) were assessed. Intrinsic subtyping, module scores covering different cancer pathways and immune-related genes were calculated for pretreated and posttreated tumors. The differences in intrinsic subtypes after NET were comparable between the two cohorts, with most Luminal B (90.0% in the POETIC trial and 76.3% in NeoAI) and 50.0% of HER2 enriched at baseline reclassified as Luminal A or normal-like after NET. Downregulation of proliferative-related pathways was observed after 2 weeks of AIs. However, more changes in genes from cancer-signaling pathways such as MAPK and PI3K/AKT/mTOR and immune response/immune-checkpoint components that were associated with AI-resistant tumors and differential outcome were observed in the NeoAI study. Tumor transcriptional profiles undergo bigger changes in response to longer NET. Changes in HER2-enriched and Luminal B subtypes are similar between the two cohorts, thus AI-sensitive intrinsic subtype tumors associated with good survival might be identified after 2 weeks of AI. The changes of immune-checkpoint component expression in early AI resistance and its impact on survival outcome warrants careful investigation in clinical trials.
Identifiants
pubmed: 34965950
pii: 1078-0432.CCR-21-2718
doi: 10.1158/1078-0432.CCR-21-2718
pmc: PMC7612503
mid: EMS140645
doi:
Substances chimiques
Aromatase Inhibitors
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
1217-1228Subventions
Organisme : Cancer Research UK
ID : 8671
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A15955
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A8671
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A8962
Pays : United Kingdom
Organisme : Cancer Research UK
ID : CRUK/07/015
Pays : United Kingdom
Informations de copyright
©2021 The Authors; Published by the American Association for Cancer Research.
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