Genetic mutations predict breast cancer relapse

By Kate Bass, B.Sc.Sep 27 2015

A large genetics study has identified genetic mutations specific to recurrent breast cancer cells. Screening for these mutations in breast cancer tumours could therefore allow doctors to identify patients most at risk of their cancer returning. The relevant genes can then be targeted to prevent recurrence of the cancer.

Treatment advances mean that most patients diagnosed with breast cancer are cured. However, in about one fifth of cases the tumour returns. The cancer can reappear either at the site of the original tumour or can spread to other parts of the body (metastasis). The latest research has shown that these recurrent cancers have different DNA sequences from those cancers that do not recur.

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Researchers at the Wellcome Trust Sanger Institute, Cambridge, UK analysed the genetic sequences of primary and recurring tumours breast cancer tumours from 1,000 patients. The study is the largest and most comprehensive of its kind and investigated 365 cancer-related genes. It showed that there were genetic differences between primary and recurring tumours, some of which were acquired when the cancer recurred and started to spread.

This suggests that it may be necessary to take repeat samples of tumour tissue, rather than basing treatment solely on the sample taken at diagnosis. Thus, if and when the tumour genetics change, the treatment can be modified to target the particular genetic mutation that is present.

Lead researcher Lucy Yates MD explained "We have found that some of the genetic mutations that drive breast cancers that relapse are relatively uncommon amongst cancers that do not relapse at the point of primary diagnosis. We believe that the differences we have seen reflect genetic differences that can predispose a cancer to return, combined with mutations acquired throughout the period from first diagnosis to the subsequent relapse. Some of these genetic alterations are potentially targetable with drugs".

Some of the later stage mutations that were found in recurrent tumours involved the JAK gene. Enhanced JAK signalling is known to be advantageous for breast cancer growth and survival. Clinical trials are already assessing the potential of JAK inhibitors to slow down breast cancer progression.

Professor Peter Naredi, scientific co-chair of the ECCO Congress where the research is to be presented, commented: "Information such as that which Dr Yates will present is very important in the era of precision medicine. Not only can we better choose the right treatment combination as our information about the primary tumour increases, and hence prevent over-treating patients who will not benefit, but this will also help us select the right therapy for each breast cancer patient.