학술논문
Molecular profiling of aromatase inhibitor sensitive and resistant ER+HER2- postmenopausal breast cancers.
Document Type
Academic Journal
Author
Schuster EF; The Breast Cancer Now Toby Robins Research Centre at the Institute of Cancer Research, London, UK. gene.schuster@icr.ac.uk.; Ralph Lauren Centre for Breast Cancer Research, Royal Marsden Hospital, London, UK. gene.schuster@icr.ac.uk.; Lopez-Knowles E; The Breast Cancer Now Toby Robins Research Centre at the Institute of Cancer Research, London, UK.; Ralph Lauren Centre for Breast Cancer Research, Royal Marsden Hospital, London, UK.; Alataki A; The Breast Cancer Now Toby Robins Research Centre at the Institute of Cancer Research, London, UK.; Ralph Lauren Centre for Breast Cancer Research, Royal Marsden Hospital, London, UK.; Zabaglo L; UK NEQAS ICC & ISH, London, UK.; Folkerd E; The Breast Cancer Now Toby Robins Research Centre at the Institute of Cancer Research, London, UK.; Ralph Lauren Centre for Breast Cancer Research, Royal Marsden Hospital, London, UK.; Evans D; UK NEQAS ICC & ISH, London, UK.; Sidhu K; UK NEQAS ICC & ISH, London, UK.; Cheang MCU; Clinical Trials and Statistics Unit, Division of Clinical Studies, The Institute of Cancer Research, London, UK.; Tovey H; Clinical Trials and Statistics Unit, Division of Clinical Studies, The Institute of Cancer Research, London, UK.; Salto-Tellez M; Precision Medicine Centre of Excellence, The Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, UK.; Cellular Pathology, Belfast Health and Social Care Trust, Belfast City Hospital, Belfast, UK.; Division of Molecular Pathology, The Institute of Cancer Research, London, UK.; Maxwell P; Precision Medicine Centre of Excellence, The Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, UK.; Robertson J; Faculty of Medicine & Health Sciences, Queen's Medical Centre, Nottingham, UK.; Smith I; Royal Marsden Hospital, London, UK.; Bliss JM; Clinical Trials and Statistics Unit, Division of Clinical Studies, The Institute of Cancer Research, London, UK.; Dowsett M; Royal Marsden Hospital, London, UK.
Source
Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
Subject
Language
English
Abstract
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.
(© 2023. The Author(s).)
(© 2023. The Author(s).)