Genetic profiling of breast cancers -- still some way from personalized medicine

November 17, 2011

Genetic profiling has revolutionised our understanding of breast cancer, but despite offering great promise to better predict outcomes and optimise treatment for individual patients, a decade on, our ability to individualise therapy based on robust prognostic and predictive factors remains limited, according to the second paper in The Lancet Series on breast cancer.

In this paper, Jorge Reis-Filho from The Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research, London, UK, and Lajos Pusztai from MD Anderson Cancer Center, Texas, USA, review the progress made in expression profiling (microarray analysis) of breast cancers over the past decade.

Despite the development of many prognostic and predictive signatures, there are currently no commercially available molecular tests to predict benefit from a specific therapeutic agent, and it is still not possible to accurately determine prognosis or chemotherapy success in some disease subsets, such as ER-negative and triple negative disease.

Traditionally, treatment decisions have been based on several clinical factors such as the location and size of the tumour, if the cancer has spread to lymph nodes or distant sites of the body, and oestrogen receptor (ER) status: "With these approaches, about 60% of all patients with early-stage breast cancer still receive adjuvant chemotherapy, of which only a small proportion, 2-15% of patients, will ultimately derive benefit, while all remain at risk of toxic side-effects", explain the authors.

The advent of first generation prognostic gene signatures has provided clinically useful additional prognostic information to that offered by clinicopathological features. Currently, several genomic tests are used in women with ER-positive disease to help define how likely it is their cancer will return and which patients have such a good outcome that they do not need chemotherapy.

But, say the authors: "Increasingly clear is that the prognostic information offered by these [first generation prognostic] signatures in addition to the information provided by semiquantitaive analysis of ER, PR, HER2, and Ki67 is limited...and the continued importance of standardised histopathological analysis of tumours should be emphasised."

The use of gene signatures to predict who might benefit from specific therapies has been less successful. Although many predictive signatures have been developed, some have been based on unreliable data, and their usefulness in patients remains controversial.

One of the reasons is that resistance to chemotherapy is a complex phenomenon, which can be caused by alterations in just one or a few genes. It is unlikely that the diverse and often subtle alterations that result in resistance to chemotherapy would be reliably picked up by standard gene expression profiling.

The authors conclude: "The theoretical knowledge and logistical lessons learned from gene expression profiling studies, however, will prove useful for research aiming to develop the next generation of prognostic and predictive biomarkers."
-end-
Professor Jorge Reis-Filho, The Institute of Cancer Research, London, UK. Via Jane Bunce, ICR Press Office T) +44 (0) 207 153 5106 E) Jorge.reis-filho@icr.ac.uk / Jane.Bunce@icr.ac.uk

Lancet

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