Cited1 as a Marker of Favourable Outcome in Anti-endocrine Treated Erα-positive, Lymph Node Negative Breast Cancer

OBJECTIVE: We present our observations of CITED1 as a potential biomarker of anti-endocrine treatment response and recurrence in breast cancer and suggest that this is dependent on its role in mediating a specific ERα transcriptional response. The study is a continuation of earlier work establishing the role of CITED1 in mammary gland development. RESULTS: CITED1 mRNA is associated with ER-positivity and selectively expressed in the GOBO dataset of cell lines and tumours representing the luminal-molecular subtype. In patients treated with tamoxifen, higher CITED1 correlated with better outcome, suggesting a role in anti-estrogen treatment response. The effect was particularly evident in the subset of ER+, lymph node negative patients and noticeable divergence of the groups was apparent only after at least 5 years. TMA analysis further validated the association of CITED1 protein, by IHC, with favourable outcome in ER+, tamoxifen-treated tumours. Although we also found a favourable response to anti-endocrine treatment in a larger TCGA dataset, the tamoxifen-specific effect was not replicated. MCF7s overexpressing CITED1 showed selective amplification of AREG but not TGFα suggesting that maintenance of specific ERα-CITED1 mediated transcription is important for the long-term response to anti-endocrine therapy and that CITED1 could potentially be utilized as a prognostic biomarker.