Aggressive prostate cancer linked to faulty BRCA2 gene

New research has revealed why men with a family history of prostate cancer, and who also carry the BRCA2 gene fault, have a more aggressive form of prostate cancer.

The study, led by Monash University’s Biomedicine Discovery Institute with Peter MacCallum Cancer Centre and the Princess Margaret Cancer Centre in Toronto, Canada, revealed that the molecular profile of the prostate cancers in men with the faulty BRCA2 gene is similar to the profile seen in patients with advanced cancer. This also helps explain why BRCA2 patients tend to have poorer treatment outcomes.

Previously, a larger Victorian Cancer Agency funded program reported that men who carry the BRCA2 gene fault are at a higher risk of having a more aggressive form of prostate cancer if a cell pathology known as IDCP (intraductal carcinoma of the prostate) is present. The IDCP cell pathology predicted these men are much more likely to have a poor clinical outcome.

The new study, published last week in Nature Communications, showed that early stage untreated prostate cancers were genetically similar to cancers that are usually seen in men with more advanced cancer that has spread to other parts of the body.

This finding was in contrast to the cancers seen in men who don’t carry a BRCA2 gene fault and who rarely have cancer spread at diagnosis. The findings were confirmed when comparing data with a companion study led by the Toronto group, which looked at prostate cancer tissue samples from more than 320 patients with prostate cancer who don’t carry a BRCA2 gene fault.

Put together, these studies identified why the presence of the BRCA2 gene fault led to markedly different clinical outcomes, with the disease progressing rapidly in those with the faulty gene.

“This study shows how different these tumours are from ‘regular’ tumours and emphasises the importance of men knowing if they have a family history of prostate, breast or ovarian cancer in their family and may carry the BRCA2 gene fault,” said Professor Gail Risbridger, Director of Monash Partners Comprehensive Cancer Consortium and Monash BDI.

Associate Professor and Director of Genitourinary Oncology at the Peter MacCallum Cancer Centre, Dr Declan Murphy, highlighted possible therapeutic implications.

“We now know that the BRCA2 fault is seen in many more men presenting with advanced prostate cancer than previously realised. Also, as prostate cancer progresses, the BRCA2 fault begins to develop in prostate cancer secondaries, and drives the aggressive behaviour of the cancer.

Therefore these new findings detailing the genomic instability of BRCA2 prostate cancer are important as we may be able to target this with new therapies,” he said.

This news post was originally published by Peter MacCallum Cancer Centre.

The Australian Cancer Research Foundation has supported cancer research at the Victorian Comprehensive Cancer Centre, Peter MacCallum Cancer Centre and Monash University by providing in total AUD $17.2 million towards cutting edge cancer research technology.