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Breast cancer intratumour heterogeneity: current status and clinical implications

Joseph, Chitra; Papadaki, Athanasia; Althobiti, Maryam; Alsaleem, Mansour; Aleskandarany, Mohammed A.; Rakha, Emad A.


Athanasia Papadaki

Maryam Althobiti

Mansour Alsaleem

Mohammed A. Aleskandarany

Professor of Breast Cancer Pathology


Breast cancer (BC) is a heterogeneous disease that varies in presentation, morphological features, behaviour, and response to therapy. High?throughput molecular profiling studies have revolutionised our understanding of BC heterogeneity, and have demonstrated that molecular profiles of tumours are variable not only between tumours, but also within individual tumours. Current evidence indicates that spatial and temporal intratumour heterogeneity of BC exists at levels beyond what are commonly expected. Intratumour heterogeneity poses critical challenges in the diagnosis, prediction of behaviour and management of BC. For instance, heterogeneous expression of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 can be seen not only in primary tumours between different regions, but also between primary tumours and their corresponding metastatic/recurrent lesions. The demonstration of molecularly distinct subclones within individual tumours may explain, at least in part, the mechanisms controlling the variable behaviour of BC, and may change our approach to BC sampling and treatment. In this review, BC intratumour heterogeneity is highlighted, with a special emphasis on the current knowledge pertaining to the relationship between intratumour heterogeneity and BC pathogenesis, evolution, and progression, with consideration of its impact on disease diagnosis, management, and the emergence of novel therapeutic targets. The key role of high?throughput molecular and imaging techniques is also addressed.


Joseph, C., Papadaki, A., Althobiti, M., Alsaleem, M., Aleskandarany, M. A., & Rakha, E. A. (2018). Breast cancer intratumour heterogeneity: current status and clinical implications. Histopathology, 73(5), (717-731). doi:10.1111/his.13642. ISSN 0309-0167

Journal Article Type Article
Acceptance Date May 2, 2018
Online Publication Date Jul 8, 2018
Publication Date 2018-11
Deposit Date Oct 25, 2018
Journal Histopathology
Print ISSN 0309-0167
Electronic ISSN 1365-2559
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 73
Issue 5
Pages 717-731
Keywords Breast cancer; Heterogeneity; Intratumour; Molecular; Targeted therapy
Public URL
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