title: Molecular assays in breast cancer pathology.
abstract: Recent advances in understanding the molecular pathology of breast cancer offer significant potential to identify patients who may benefit from adjuvant therapies. To date, few of these advances are utilised in a routine setting. We review molecular assays that are currently in use or are in the advanced stages of development, which may be used as predictive or prognostic biomarkers in breast cancer.The only widely used breast cancer molecular assay is in situ hybridisation (ISH) for human epidermal growth factor receptor 2 (HER2) gene amplification and we highlight key issues with the interpretation of this assay, with particular attention to the difficulties of the equivocal category. New molecular assays such as ISH for the topoisomerase II alpha (TOP2A) gene and for the aberrations in the copy number of the centromeric region of chromosome 17 are readily performed in a standard histopathology laboratory, but to date there are insufficient data to support their routine use. We also review the current data on two commercially available multigene expression assays, Oncotype DX and MammaPrint and discuss their potential use. Overall, while new molecular assays have significant potential to improve patient selection for therapy, well-performed histopathology with reliable interpretation of standard hormone and HER2 assays provides the most important predictive and prognostic information in early breast cancer.
authors.affiliation: Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia. s.otoole@garvan.org.au
authors.forename: Sandra A
authors.initials: SA
authors.lastname: O'Toole
authors.forename: Christina I
authors.initials: CI
authors.lastname: Selinger
authors.forename: Ewan K A
authors.initials: EK
authors.lastname: Millar
authors.forename: Trina
authors.initials: T
authors.lastname: Lum
authors.forename: Jane M
authors.initials: JM
authors.lastname: Beith
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics; D001943:Breast Neoplasms / Q000473:pathology*; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17; D004250:DNA Topoisomerases, Type II / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D020869:Gene Expression Profiling; D018734:Genes, erbB-2 / Q000502:physiology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D025202:Molecular Diagnostic Techniques; D021141:Nucleic Acid Amplification Techniques / Q000379:methods*; D000075223:Poly-ADP-Ribose Binding Proteins; D011379:Prognosis
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human