Impact of mutational profiles on response of primary oestrogen receptor-positive breast cancers to oestrogen deprivation

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 SkeneWilliam Maxwell, John Robertson, Judith M Bliss, Ian Smith, Mitch Dowsett, POETIC Trial Management Group and Trialists

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)
241 Downloads (Pure)


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.

Original languageEnglish
Article number13294
JournalNature Communications
Early online date09 Nov 2016
Publication statusEarly online date - 09 Nov 2016
Externally publishedYes

Bibliographical note

Author contribution:


  • Journal Article

Fingerprint Dive into the research topics of 'Impact of mutational profiles on response of primary oestrogen receptor-positive breast cancers to oestrogen deprivation'. Together they form a unique fingerprint.

Cite this