Impact of mutational profiles on response of primary oestrogen receptor-positive breast cancers to oestrogen deprivation
Year: 2016
Type: article
Abstract: Pre-surgical studies allow study of the relationship between mutations and response of oestrogen receptor-positive (ER+) breast cancer to aromatase inhibitors (AIs) but have been limited to small biopsies. Here in phase I of this study, we perform exome sequencing on baseline, surgical core-cuts and blood from 60 patients (40 AI treated, 20 controls). In poor responders (based on Ki67 change), we find significantly more somatic mutations than good responders. Subclones exclusive to baseline or surgical cores occur in ∼30% of tumours. In phase II, we combine targeted sequencing on another 28 treated patients with phase I. We find six genes frequently mutated: PIK3CA, TP53, CDH1, MLL3, ABCA13 and FLG with 71% concordance between paired cores. TP53 mutations are associated with poor response. We conclude that multiple biopsies are essential for confident mutational profiling of ER+ breast cancer and TP53 mutations are associated with resistance to oestrogen deprivation therapy.
Source: Nature Communications
DOI: 10.1038/ncomms13294
Authors: Pascal Gellert, Corrinne V. Segal, Qiong Gao, Elena López-Knowles, Lesley-Ann Martin, Andrew Dodson, Tiandao Li, Christopher A. Miller, Charles Lu, Elaine R. Mardis, Alexa Gillman, James Morden, Manuela Graf, Kally Sidhu, Abigail Evans, Michael Shere, Christopher Holcombe, Stuart A. McIntosh, Nigel Bundred, Anthony Skene, William Maxwell, John Robertson, Judith M. Bliss, Ian Smith, Mitch Dowsett, POETIC Trial Management Group and Trialists, Stephen Johnston, Radha Todd, Kieran Horgan, Stephen Chan, Simon D. H. Holt, Marina Parton, Ian Laidlaw, Jayant S. Vaidya, Tracey Irvine, Fiona Hoar, Ilyas Khattak, Ashutosh Kothari, Lucy Brazil, Nicholas Gallegos, Duncan Wheatley, Tayo Johnson, Geoffrey Sparrow, Serena Ledwidge, Caroline Mortimer, Marcus Ornstein, Douglas Ferguson, Douglas Adamson, Ramsey Cutress, Richard Johnson, Clare Crowley, Zoe Winters, Hisham Hamed, Russell Burcombe, Susan Cleator, Muireann Kelleher, Jonathan Roberts, Sarah Vesty, Maher Hadaki, Mary Quigley, Julie Doughty, Siobhan Laws, Seema Seetharam, Amanda Thorne, Peter Donnelly
Institutions: Institute of Cancer Research, Breast Cancer Now, Royal Marsden Hospital, Washington University in St. Louis, Poole Hospital, Southmead Hospital, Royal Liverpool University Hospital, Queen's University Belfast, Royal Bournemouth Hospital, Withybush General Hospital, University of Nottingham, Royal Victoria Infirmary, St James's University Hospital, Nottingham City Hospital, Prince Philip Hospital, Frimley Park Hospital, Whittington Hospital, Royal Surrey County Hospital, Birmingham City Hospital, Ysbyty Gwynedd Hospital NHS Trust, Guy's Hospital, Weston General Hospital, Royal Cornwall Hospital, St Peter's Hospital, Yeovil District Hospital NHS Foundation Trust, Yeovil District Hospital, St Bartholomew's Hospital, Ipswich Hospital, Homerton University Hospital, Royal Devon and Exeter Hospital, Ninewells Hospital, Southampton General Hospital, Neath Port Talbot Hospital, Salisbury District Hospital, Bristol Royal Infirmary, Maidstone Hospital, St Mary's Hospital, Tunbridge Wells Hospital, St George's Hospital, Charing Cross Hospital, King's College Hospital, Cheltenham General Hospital, Queen's Hospital, Western Infirmary, Royal Hampshire County Hospital, Darent Valley Hospital, Musgrove Park Hospital, Taunton & Somerset NHS Foundation Trust, Torbay Hospital
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W2550144082