Mutations may predict breast cancer relapse

Researchers have identified genetic differences in breast cancers that relapse and those that do not, suggesting that the finding could be used to help doctors identify patients most at risk of their cancer returning.

By examining the DNA of breast cancer tumours from 1000 patients, including 161 cases of returning tumours or ones that had spread, scientists at the Sanger Institute, Cambridge observed that some mutations occurred significantly more often in relapse than in primary samples.

Lead author Dr Lucy Yates said: '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.'

In around 20 percent of breast cancer cases the patient relapses and growth of the tumour recurs, either at the original site or in metastases.  It is not known, however, if primary tumours that relapse can be identified at initial diagnosis by their genetics, or if mutations are acquired after initial treatment that may affect the response of new tumours to chemotherapy.

This study, which the researchers claim is the largest and most comprehensive to date, investigating 365 cancer-related genes in a large number of tumours, found that mutations identified in tumours that had relapsed were relatively uncommon in cancers diagnosed first time and did not relapse.

Dr Yates believes that these differences are down to genetic changes that may predispose a tumour to relapse, as well as changes that occur since the primary diagnosis due to environmental factors, such as the response of the immune system, treatments for cancer or the area of the body where
the cancer returns.

The researchers also identified include mutations in regulatory and signalling pathways, suggesting that the secondary tumours may be working differently than in other cancers.

Due to a low number of primary and relapse samples from the same patient, the study was also not able to determine which mutations in the relapsing tumours were also consistently present in primary lesions, however, and could therefore be used diagnostically at the start of treatment.

Dr Yates told BBC News: 'Further work is needed to validate these findings in much larger datasets, but we hope that in the future it will be possible at the point of diagnosis to look at the cancer genes in an individual's cancer and determine whether it is likely to return in the future and, if so, to select a personalised therapy to prevent that event.'