title: Quantification of HER2 heterogeneity in breast cancer-implications for identification of sub-dominant clones for personalised treatment.
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.
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University, Belfast, UK.
authors.forename: Niamh E
authors.initials: NE
authors.lastname: Buckley
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University, Belfast, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Forde
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University, Belfast, UK.
authors.forename: Darragh G
authors.initials: DG
authors.lastname: McArt
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University, Belfast, UK.|Tissue Pathology, Belfast Health and Social Care Trust, Belfast City Hospital, Lisburn Road., Belfast, UK.
authors.forename: David P
authors.initials: DP
authors.lastname: Boyle
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University, Belfast, UK.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Mullan
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University, Belfast, UK.|Tissue Pathology, Belfast Health and Social Care Trust, Belfast City Hospital, Lisburn Road., Belfast, UK.
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: James
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University, Belfast, UK.|Tissue Pathology, Belfast Health and Social Care Trust, Belfast City Hospital, Lisburn Road., Belfast, UK.
authors.forename: Perry
authors.initials: P
authors.lastname: Maxwell
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University, Belfast, UK.|Tissue Pathology, Belfast Health and Social Care Trust, Belfast City Hospital, Lisburn Road., Belfast, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: McQuaid
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University, Belfast, UK.|Tissue Pathology, Belfast Health and Social Care Trust, Belfast City Hospital, Lisburn Road., Belfast, UK.
authors.forename: Manuel
authors.initials: M
authors.lastname: Salto-Tellez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000145:classification* / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D002999:Clone Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D057285:Precision Medicine; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human