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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.

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


Authors

Mohammed A. Aleskandarany

Devika Agarwal

Somaia Elsheikh

Christopher C. Nolan

Maria Diez-Rodriguez

R. Douglas Macmillan

Graham R. Ball

Carlos Caldas

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