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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


Sergey Klimov

Padmashree C.G. Rida

Mohammed A. Aleskandarany

Emiel A.M. Janssen

Professor of Breast Cancer Pathology

Ritu Aneja


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
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.


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.

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
Public URL
Publisher URL


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