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Molecular profiling of aromatase inhibitor sensitive and resistant ER+HER2- postmenopausal breast cancers
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Molecular profiling of aromatase inhibitor sensitive and resistant ER+HER2- postmenopausal breast cancers
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Journal Article
Molecular profiling of aromatase inhibitor sensitive and resistant ER+HER2- postmenopausal breast cancers
2023
Overview
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.
Aromatase inhibitors are an effective treatment for ER+ breast cancer, but response is variable. Here, the authors undertake molecular analyse of response from the POETIC trial and identify several factors associated with response.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/51
/ 14
/ 140/58
/ 38/91
/ 45
/ 45/23
/ 49
/ Aromatase Inhibitors - pharmacology
/ Aromatase Inhibitors - therapeutic use
/ Breast Neoplasms - drug therapy
/ Breast Neoplasms - metabolism
/ Female
/ Humanities and Social Sciences
/ Humans
/ Receptor, ErbB-2 - metabolism
/ Receptors, Estrogen - genetics
/ Receptors, Estrogen - metabolism
/ Science
/ Tumors
