Molecular assays in breast cancer pathology - Introduction

A Special Author Introduction
Pathology
ISSN: 0031-3025 • Frequency: 7/year • Impact Factor 2.673 • Subscribe Now

By Sandra O'Toole

Breast cancer is a heterogeneous disease, with considerable variability in clinical outcome, the prognosis and management of which is largely based on histopathological features accompanied by established biomarkers of hormone receptor status, estrogen and progesterone receptors (ER, PR), and HER-2 amplification. ER+ disease comprises approximately 70% of cases and therapies targeting estrogen synthesis or the ER are the most effective treatments with adjuvant tamoxifen/aromatase inhibitors reducing the annual risk of recurrence and death by up to 47% and 26% respectively. More recently trastuzumab has been shown to have a significant benefit in the treatment of one of the most aggressive types of breast cancer, HER2 amplified tumours. ER and PR have been in use as biomarkers for at least 20 years and virtually all early breast cancers in Australia for the past 4 years have been evaluated for HER2 gene amplification status. A major goal of "molecular" personalised medicine is to use stringently validated and reproducible laboratory assays of biomarkers that stratify patients into optimal treatment regimens. Thus, breast cancer management presents a model of "personalized medicine" for other malignancies to follow which has lead to significant improvements in disease outcome.

However, although there are several thousand papers evaluating various biomarkers in breast cancer, to date less than a handful of single gene markers are in routine use. This is not entirely surprising as cancer often involves aberrations in many genes and multiple pathways can be defective thus it is less likely that single genes may accurately predict outcome and response to therapy in such complex systems. The advent of gene expression profiling technology allows for the relatively affordable screening of the relative abundance of messenger RNA transcripts in cancer tissue, representing the entire genome.

An increasing number of diagnostic tools that make use of gene expression signatures are now available to assess patient risk and survival as well as the benefit of adjuvant therapy. These tools promise improved identification of patients who will benefit from treatment and those patients who could be spared unnecessary treatment. Many large microarray studies have controversially differed in the relative abundance of top genes involved in breast cancer with relatively little overlap between them possibly due to differences in array platforms and methodologies of data analysis. One way to resolve this is to use standardised methods, a feature that commercialised diagnostic testing can provide.
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; 2 single gene assays using in situ hybridisation (ISH) for HER2 and Topoisomerase II alpha (TOP2A) as well as two commercially available multigene expression assays, Oncotype DX and MammaPrint.

We conclude that while new molecular assays have significant potential to improve patient selection for therapy, well-performed histopathology with reliable interpretation of standard hormone receptors, grade and HER2 assays provides the most important predictive and prognostic information in early breast cancer.

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This article was originally published in Pathology, to read more research in this field please visit: www.rcpa-pathologyjournal.com