MYC functions are specific in biological subtypes of breast cancer and confers resistance to endocrine therapy in luminal tumours

Green, Andrew R.; Aleskandarany, Mohammed A.; Agarwal, Devika; Elsheikh, Somaia; Nolan, Christopher C.; Diez-Rodriguez, Maria; Macmillan, R. Douglas; Ball, Graham R.; Caldas, Carlos; Madhusudan, Srinivasan; Ellis, Ian O.; Rakha, Emad A.

doi:10.1038/bjc.2016.46

MYC functions are specific in biological subtypes of breast cancer and confers resistance to endocrine therapy in luminal tumours

Green, Andrew R.; Aleskandarany, Mohammed A.; Agarwal, Devika; Elsheikh, Somaia; Nolan, Christopher C.; Diez-Rodriguez, Maria; Macmillan, R. Douglas; Ball, Graham R.; Caldas, Carlos; Madhusudan, Srinivasan; Ellis, Ian O.; Rakha, Emad A.

Authors

ANDREW GREEN andrew.green@nottingham.ac.uk
Associate Professor

Mohammed A. Aleskandarany

Devika Agarwal

Somaia Elsheikh

Christopher C. Nolan

Maria Diez-Rodriguez

R. Douglas Macmillan

Graham R. Ball

Carlos Caldas

SRINIVASAN MADHUSUDAN srinivasan.madhusudan@nottingham.ac.uk
Professor of Medical Oncology

Professor IAN ELLIS IAN.ELLIS@NOTTINGHAM.AC.UK
Professor of Cancer Pathology

EMAD RAKHA Emad.Rakha@nottingham.ac.uk
Professor of Breast Cancer Pathology

Abstract

Background:

MYC is amplified in approximately 15% of breast cancers (BCs) and is associated with poor outcome. c-MYC protein is multi-faceted and participates in many aspects of cellular function and is linked with therapeutic response in BCs. We hypothesised that the functional role of c-MYC differs between molecular subtypes of BCs.

Methods:

We therefore investigated the correlation between c-MYC protein expression and other proteins involved in different cellular functions together with clinicopathological parameters, patients’ outcome and treatments in a large early-stage molecularly characterised series of primary invasive BCs (n=1106) using immunuohistochemistry. The METABRIC BC cohort (n=1980) was evaluated for MYC mRNA expression and a systems biology approach utilised to identify genes associated with MYC in the different BC molecular subtypes.

Results:

High MYC and c-MYC expression was significantly associated with poor prognostic factors, including grade and basal-like BCs. In luminal A tumours, c-MYC was associated with ATM (P=0.005), Cyclin B1 (P=0.002), PIK3CA (P=0.009) and Ki67 (P

Citation

Green, A. R., Aleskandarany, M. A., Agarwal, D., Elsheikh, S., Nolan, C. C., Diez-Rodriguez, M., …Rakha, E. A. (2016). MYC functions are specific in biological subtypes of breast cancer and confers resistance to endocrine therapy in luminal tumours. British Journal of Cancer, 114(8), 917-928. https://doi.org/10.1038/bjc.2016.46

Journal Article Type	Article
Acceptance Date	Feb 9, 2016
Online Publication Date	Mar 8, 2016
Publication Date	2016-04
Deposit Date	Oct 16, 2018
Publicly Available Date	Oct 18, 2018
Journal	British Journal of Cancer
Print ISSN	0007-0920
Electronic ISSN	1532-1827
Publisher	Cancer Research UK
Peer Reviewed	Peer Reviewed
Volume	114
Issue	8
Pages	917-928
DOI	https://doi.org/10.1038/bjc.2016.46
Public URL	https://nottingham-repository.worktribe.com/output/1169998
Publisher URL	https://www.nature.com/articles/bjc201646