Additional prognostic value of OncoMasTR multigene prognostic signature to clinicopathological information in patients with HR-positive, HER2-negative, lymph node-negative breast cancer from the TAILORx Tissue Bank, Ireland.

person Darran O'Connor Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland info_outline Darran O'Connor, Catherine Margaret Kelly, John Crown, Niamh Russell, Stephen Barron, Tony Loughman, Seodhna Lynch, Anthony O'Grady, Katherine M Sheehan, Joanna Fay, Anurati Saha, Peter Dynoodt, Bozena Fender, Chan-Ju Angel Wang, Desmond O'Leary, Adrian P. Bracken, Arman Rahman, Claudia Aura Gonzalez, Nebras Al Attar, William M. Gallagher

Authors person Darran O'Connor Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland info_outline Darran O'Connor, Catherine Margaret Kelly, John Crown, Niamh Russell, Stephen Barron, Tony Loughman, Seodhna Lynch, Anthony O'Grady, Katherine M Sheehan, Joanna Fay, Anurati Saha, Peter Dynoodt, Bozena Fender, Chan-Ju Angel Wang, Desmond O'Leary, Adrian P. Bracken, Arman Rahman, Claudia Aura Gonzalez, Nebras Al Attar, William M. Gallagher Organizations Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland, Mater Misericordiae University Hospital, Dublin, Ireland, NSABP/NRG Oncology, and The Irish Cooperative Oncology Research Group, Dublin, Ireland, UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, Dublin, Ireland, OncoMark Limited, Dublin, Ireland, OncoMark Ltd, Dublin, Ireland, Department of Histopathology, Beaumont Hospital, Dublin, Ireland, RCSI Education and Research Centre, Dublin, Ireland, Cancer Trials Ireland, Dublin, Ireland, Oncomark Ltd, Dublin, Ireland, Smurfit Institute of Genetics, Dublin, Ireland, Conway Institute, UCD, Dublin, Ireland, Cancer Biology and Therapeutics Laboratory, Dublin, Ireland Abstract Disclosures Research Funding Other Foundation Background: Multigene prognostic signatures (MGPS) can identify early stage breast cancer patients who may require less aggressive treatment. To be clinically useful, MGPSs must provide additional prognostic information to clinicopathological information routinely used by clinicians. The OncoMasTR MGPS was discovered via a novel bioinformatic transcriptional network analysis. OncoMasTR consists of genes – Master Transcription Regulators (MTRs) – that regulate previously known prognostic genes and have identified functional roles in several hallmarks of cancer including proliferation, invasion and metastasis. The OncoMasTR Molecular Score (OM) consists of just 3 MTRs. The OncoMasTR Risk Score (OncoMasTR) combines OM with lymph node status and tumour size, and categorises patients as low or high risk. The OncoMasTR Test has been analytically and clinically validated. Methods: MTR expression was measured by RT-qPCR in tissue from 404 patients enrolled in an independent translational trial (NCT02050750) that collected tissue and clinical data from patients enrolled in TAILORx in Ireland. OM, OncoMasTR and Oncotype DX Recurrence Score (RS) were compared on the additional prognostic value they provided to Ki67, Nottingham Prognostic Index (NPI) and other clinicopathological information for distant recurrence (DR) and invasive disease (ID). Results: OM (LRχ 2 = 20.3, p < 0.00001, c-index = 0.84) and OncoMasTR (LRχ 2 = 22.6, p < 0.00001, c-index = 0.85) were significantly prognostic, and more prognostic than RS (LRχ 2 = 8.4, p = 0.004, c-index = 0.73) for DR. OM and OncoMasTR provided more additional prognostic information than RS to Ki67, NPI, tumour size, tumour grade, and age for DR. Similar results were found when OM, OncoMasTR and RS were compared on prognostic performance for ID. Conclusions: OM and OncoMasTR were significantly prognostic for DR and ID and added significant prognostic value to Ki67, NPI, and other clinicopathological information. Furthermore, OM and OncoMasTR showed superior prognostic performance to RS.