Molecular profiling of aromatase inhibitor sensitive and resistant ER+HER2- postmenopausal breast cancers.
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Date
2023-07-07ICR Author
Author
Schuster, EF
Lopez-Knowles, E
Alataki, A
Zabaglo, L
Folkerd, E
Evans, D
Sidhu, K
Cheang, MCU
Tovey, H
Salto-Tellez, M
Maxwell, P
Robertson, J
Smith, I
Bliss, JM
Dowsett, M
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Research team
Endocrine Therapy Resist
Endocrinology
Language
eng
Date accepted
2023-06-15
License start date
2023-07-07
Citation
Nature Communications, 2023, 14 (1),
Publisher
NATURE PORTFOLIO