Recent advances in systemic therapy: new diagnostics and biological predictors of outcome in early breast cancer

Abstract

The key to optimising our approach in early breast cancer is to individualise care. Each patient has a tumour with innate features that dictate their chance of relapse and their responsiveness to treatment. Often patients with similar clinical and pathological tumours will have markedly different outcomes and responses to adjuvant intervention. These differences are encoded in the tumour genetic profile. Effective biomarkers may replace or complement traditional clinical and histopathological markers in assessing tumour behaviour and risk. Development of high-throughput genomic technologies is enabling the study of gene expression profiles of tumours. Genomic fingerprints may refine prediction of the course of disease and response to adjuvant interventions. This review will focus on the role of multiparameter gene expression analyses in early breast cancer, with regards to prognosis and prediction. The prognostic role of genomic signatures, particularly the Mammaprint and Rotterdam signatures, is evolving. With regard to prediction of outcome, the Oncotype Dx multigene assay is in clinical use in tamoxifen treated patients. Extensive research continues on predictive gene identification for specific chemotherapeutic agents, particularly the anthracyclines, taxanes and alkylating agents.

Figure 1

Outline of the TRANSBIG MINDACT trial. Clin-path, clinical-pathological; CT, chemotherapy; HT, hormone therapy; y, year.

Figure 2

The 21 genes identified for Oncotype Dx: 16 cancer related genes and 5 reference genes. These are used to calculate a Recurrence Score [22].

Figure 3

Multifactorial regulation of topoisomerase IIa (TopoIIa). TopoIIa gene transcription is under control of gene signals and proliferative signals. Redox-sensitive protein complexes regulate mRNA half-life. Variable mRNA splicing produces protein isoforms: the cytoplasmic form is inactive, the nuclear form is active. Nuclear receptors regulate transport of these isoforms depending on the cell proliferative phase [43].