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

No Thumbnail Available

Files

NComms.pdf (1.05 MB)

Embargo End Date

ICR Authors

Gao, Qiong
 Martin, Lesley-Ann
 Gillman, Alexa
 Bliss, Judith
 Dowsett, Mitch

Authors

Gellert, P
Segal, CV
Gao, Q
López-Knowles, E
Martin, L-A
Dodson, A
Li, T
Miller, CA
Lu, C
Mardis, ER
Gillman, A
Morden, J
Graf, M
Sidhu, K
Evans, A
Shere, M
Holcombe, C
McIntosh, SA
Bundred, N
Skene, A
Maxwell, W
Robertson, J
Bliss, JM
Smith, I
Dowsett, M
POETIC Trial Management Group and Trialists,

Document Type

Journal Article

Date

2016-11-09

Date Accepted

2016-09-19

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.

Citation

Nature communications, 2016, 7 pp. 13294 - ?

DOI

10.1038/ncomms13294

URI

https://repository.icr.ac.uk/handle/internal/139

Rights

https://creativecommons.org/licenses/by/4.0

Source Title

Publisher

NATURE PORTFOLIO

ISSN

2041-1723

eISSN

2041-1723

Collections

Breast Cancer Research
Cancer Biology
Clinical Studies

Research Team

Clinical Trials & Statistics Unit
Medicine (RMH Smith Cunningham)
Endocrinology

Notes