Novel immunohistochemistry-based signatures to predict metastatic site of triple-negative breast cancers

Klimov, Sergey; Rida, Padmashree C.G.; Aleskandarany, Mohammed A.; Green, Andrew R.; Ellis, Ian O.; Janssen, Emiel A.M.; Rakha, Emad A.; Aneja, Ritu

Abstract

Background: Although distant metastasis (DM) in breast cancer (BC) is the most lethal form of recurrence and the most common
underlying cause of cancer related deaths, the outcome following the development of DM is related to the site of metastasis.
Triple negative BC (TNBC) is an aggressive form of BC characterised by early recurrences and high mortality. Athough multiple
variables can be used to predict the risk of metastasis, few markers can predict the specific site of metastasis. This study aimed at
identifying a biomarker signature to predict particular sites of DM in TNBC.
Methods: A clinically annotated series of 322 TNBC were immunohistochemically stained with 133 biomarkers relevant to BC, to
develop multibiomarker models for predicting metastasis to the bone, liver, lung and brain. Patients who experienced metastasis
to each site were compared with those who did not, by gradually filtering the biomarker set via a two-tailed t-test and Cox
univariate analyses. Biomarker combinations were finally ranked based on statistical significance, and evaluated in multivariable
analyses.
Results: Our final models were able to stratify TNBC patients into high risk groups that showed over 5, 6, 7 and 8 times higher risk
of developing metastasis to the bone, liver, lung and brain, respectively, than low-risk subgroups. These models for predicting
site-specific metastasis retained significance following adjustment for tumour size, patient age and chemotherapy status.
Conclusions: Our novel IHC-based biomarkers signatures, when assessed in primary TNBC tumours, enable prediction of specific
sites of metastasis, and potentially unravel biomarkers previously unknown in site tropism.

Citation

Klimov, S., Rida, P. C., Aleskandarany, M. A., Green, A. R., Ellis, I. O., Janssen, E. A., …Aneja, R. (2017). Novel immunohistochemistry-based signatures to predict metastatic site of triple-negative breast cancers. British Journal of Cancer, 117(6), 826-834. https://doi.org/10.1038/bjc.2017.224

• Journal Article Type: Article
• Acceptance Date: Jun 15, 2017
• Online Publication Date: Jul 18, 2017
• Publication Date: Sep 5, 2017
• Deposit Date: Oct 15, 2018
• Publicly Available Date: Oct 16, 2018
• Journal: British Journal of Cancer
• Print ISSN: 0007-0920
• Electronic ISSN: 1532-1827
• Publisher: Cancer Research UK
• Peer Reviewed: Peer Reviewed
• Volume: 117
• Issue: 6
• Pages: 826-834
• DOI: https://doi.org/10.1038/bjc.2017.224
• Public URL: https://nottingham-repository.worktribe.com/output/1166600
• Publisher URL: https://www.nature.com/articles/bjc2017224