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.

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., Macmillan, R. D., Ball, G. R., Caldas, C., Madhusudan, S., Ellis, I. O., & 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
• Contract Date: Oct 18, 2018