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

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 differ...

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Published in:British journal of cancer 2016-04, Vol.114 (8), p.917-928
Main Authors: 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
Format: Article
Language:English
Subjects:
631/67/1059/2326
631/67/1347
631/67/395
692/700/1750
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Ataxia Telangiectasia Mutated Proteins - genetics
Biomarkers, Tumor - genetics
Biomedical and Life Sciences
Biomedicine
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Cancer Research
Class I Phosphatidylinositol 3-Kinases
Cyclin B1 - genetics
Cyclin E - genetics
Disease-Free Survival
Drug Resistance
Drug Resistance, Neoplasm - genetics
Endocrine Cells - physiology
Epidemiology
Female
Gene Expression Profiling - methods
Gene Expression Regulation, Neoplastic - genetics
Humans
Molecular Diagnostics
Molecular Medicine
Oncology
Phosphatidylinositol 3-Kinases - genetics
Prognosis
Proto-Oncogene Proteins c-myc - genetics
Receptor, ErbB-2 - genetics
RNA, Messenger - genetics
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Summary: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
ISSN:0007-0920
1532-1827
DOI:10.1038/bjc.2016.46