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

ABSTRACT: 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.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 immunohistochemistry. 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.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<0.001). In contrast, in basal-like tumours, c-MYC showed positive association with Cyclin E (P=0.003) and p16 (P=0.042) expression only. c-MYC was an independent predictor of a shorter distant metastases-free survival in luminal A LN+ tumours treated with endocrine therapy (ET; P=0.013). In luminal tumours treated with ET, MYC mRNA expression was associated with BC-specific survival (P=0.001). In ER-positive tumours, MYC was associated with expression of translational genes while in ER-negative tumours it was associated with upregulation of glucose metabolism genes.c-MYC function is associated with specific molecular subtypes of BCs and its overexpression confers resistance to ET. The diverse mechanisms of c-MYC function in the different molecular classes of BCs warrants further investigation particularly as potential therapeutic targets.

SUBMITTER: Green AR

PROVIDER: S-EPMC4984797 | biostudies-other | 2016 Apr

REPOSITORIES: biostudies-other

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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 AR Aleskandarany Mohammed A MA Agarwal Devika D Elsheikh Somaia S Nolan Christopher C CC Diez-Rodriguez Maria M Macmillan R Douglas RD Ball Graham R GR Caldas Carlos C Madhusudan Srinivasan S Ellis Ian O IO Rakha Emad A EA

British journal of cancer 20160308 8

<h4>Background</h4>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.<h4>Methods</h4>We therefore investigated the correlation between c-MYC protein expression and other proteins involved in different cellular functions togeth ...[more]

PMID: 26954716

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

Publications

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

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