Quantification of HER2 heterogeneity in breast cancer-implications for identification of sub-dominant clones for personalised treatment

Niamh E Buckley, Claire Forde, Darragh G McArt, David P Boyle, Paul B Mullan, Jacqueline A James, Perry Maxwell, Stephen McQuaid, Manuel Salto-Tellez

Research output: Contribution to journalArticle

22 Citations (Scopus)
274 Downloads (Pure)

Abstract

Breast cancer is a heterogeneous disease, at both an inter- and intra-tumoural level. Appreciating heterogeneity through the application of biomarkers and molecular signatures adds complexity to tumour taxonomy but is key to personalising diagnosis, treatment and prognosis. The extent to which heterogeneity exists, and its interpretation remains a challenge to pathologists. Using HER2 as an exemplar, we have developed a simple reproducible heterogeneity index. Cell-to-cell HER2 heterogeneity was extensive in a proportion of both reported 'amplified' and 'non-amplified' cases. The highest levels of heterogeneity objectively identified occurred in borderline categories and higher ratio non-amplified cases. A case with particularly striking heterogeneity was analysed further with an array of biomarkers in order to assign a molecular diagnosis. Broad biological complexity was evident. In essence, interpretation, depending on the area of tumour sampled, could have been one of three distinct phenotypes, each of which would infer different therapeutic interventions. Therefore, we recommend that heterogeneity is assessed and taken into account when determining treatment options.

Original languageEnglish
Article number23383
Number of pages8
JournalScientific Reports
Volume6
Early online date21 Mar 2016
DOIs
Publication statusEarly online date - 21 Mar 2016

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