E-Mail karger@karger.com Tumour Heterogeneity Pathobiology 2018;85:23–34 DOI: 10.1159/000477851 Tumour Heterogeneity of Breast Cancer: From Morphology to Personalised Medicine Mohammed A. Aleskandarany a Michel E. Vandenberghe b Caterina Marchiò c Ian O. Ellis a Anna Sapino c, d Emad A. Rakha a a Department of Histopathology, University of Nottingham and Nottingham University Hospitals NHS Trust, City Hospital, Nottingham, and b Precision Medicine Laboratories, Precision Medicine and Genomics, IMED Biotech Unit, AstraZeneca, Cambridge, UK; c Department of Medical Sciences, University of Turin, Turin, and d Candiolo Cancer Institute-FPO, IRCCS, Candiolo, Italy studies and in the clinical setting. Here, we provide a brief overview of BC heterogeneity, with an emphasis on the clin- ical consequences of intratumoral heterogeneity. © 2018 S. Karger AG, Basel Introduction Breast cancer (BC) is characterised by a remarkable degree of morphological and molecular heterogeneity, not only between tumours (intertumoral heterogeneity) but also among the same tumours (intratumoral hetero- geneity). At the level of an individual patient’s tumours, heterogeneity can also be classified into “spatial” and “temporal.” Temporal heterogeneity is particularly im- portant when comparing the features of the primary tu- mour and metastatic or recurrent lesions, and pre-inva- sive and invasive disease in the same tumours. There is sufficient evidence to indicate considerable differences between the primary tumour and local or distant recur- rences that may have an impact on the treatment deci- sions for patients with recurrent disease [1–3]. Heteroge- neity in BC is the result of a co-ordinated interplay be- Keywords Breast cancer · Heterogeneity · Morphology · Molecular heterogeneity · Microenvironment · Sampling · Personalised therapy · Resistance Abstract Breast cancer (BC) displays striking clinical, morphological, and behavioural diversity within a single tumour and be- tween tumours. Currently, mounting evidence indicates that the morphological heterogeneity of BC reflects an underly- ing spectrum of genetic and epigenetic portraits that control BC behaviour. Further understanding of BC heterogeneity will have an impact, not only on the routine diagnostic prac- tices but also on patients’ management decisions. Phenom- ena like diagnostic inconsistencies and therapeutic resis- tance, both primary and acquired, could be attributed, at least in part, to tumour heterogeneity within the same can- cer and between the primary disease and subsequent recur- rences. From a practical standpoint, and to minimise the im- pact of BC intratumoral heterogeneity, pragmatic approach- es for adequate tumour sampling have been suggested in translational biomarker discovery and validation research Received: December 19, 2016 Accepted after revision: May 30, 2017 Published online: February 10, 2018 Prof. Emad A. Rakha Department of Histopathology, University of Nottingham Nottingham City Hospitals NHS Trust Hucknall Road, Nottingham, NG5 1PB (UK) E-Mail Emad.Rakha @ nottingham.ac.uk © 2018 S. Karger AG, Basel www.karger.com/pat