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Scientists Find That Prostate Cancer Patients With BRCA2 mutations Require Urgent Treatment

Men who develop after inheriting a faulty gene need immediate surgery or radiotherapy rather than being placed under surveillance, as their disease is more aggressive than other types, a new study has found.

A team at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust found spread more quickly and were more often fatal in men who had inherited a faulty BRCA2 gene than in men without the faulty gene.

The research, funded by the Ronald and Rita McAulay Foundation and Cancer Research UK, could challenge current NHS guidelines for prostate cancer, under which BRCA2 mutation carriers are offered the same treatment options as non-carriers.

It is often difficult to tell at diagnosis whether prostate cancer will be life-threatening or not, and while treatment options for early-stage disease include surgery and radiotherapy, many men instead receive active surveillance to see if the disease starts to progress.

The new study, published today (Monday) in the Journal of the Clinical Oncology, is the largest to compare prostate cancer patients with and without BRCA mutations, in order to tell whether gene testing should help to direct management options.

Senior author Professor Ros Eeles, Professor of Oncogenetics at The Institute of Cancer Research (ICR) and Honorary Consultant in Clinical Oncology at The Royal Marsden, said: “It is clear from our study that prostate cancers linked to inheritance of the BRCA2 cancer gene are more deadly than other types. It must make sense to start offering affected men immediate surgery or radiotherapy, even for early-stage cases that would otherwise be classified as low-risk. We won’t be able to tell for certain that earlier treatment can benefit men with inherited cancer genes until we’ve tested it in a clinical trial, but the hope is that our study will ultimately save lives by directing treatment at those who most need it.’

The team from the ICR and The Royal Marsden, with collaborators across the UK, examined the medical records of 61 BRCA2-mutation carriers, 18 BRCA1-mutation carriers and 1,940 non-carriers.

They found BRCA1/2 mutation carriers were more likely to be diagnosed with advanced stage prostate cancers (37 per cent versus 28 per cent) or cancer that had already spread (18 per cent versus nine per cent) than non-carriers. Among those whose cancers had not spread out of the prostate at diagnosis, within five years more carriers than non-carriers had metastatic disease (23 per cent versus seven per cent).

Patients with BRCA2-mutations were also significantly less likely to survive the cancer, living an average of 6.5 years compared with 12.9 years for non-carriers. The team concluded that a BRCA2 test could be used in combination with other factors as a prognostic test. Men with a BRCA1 mutation also had a shorter average survival time of 10.5 years, but there was not a statistically significant difference with non-carriers.

Professor Alan Ashworth, Chief Executive of The Institute of Cancer Research, said: “The BRCA2 gene was discovered here at the ICR, and the gene tests that followed have offered families with an inherited risk of prostate or breast cancer the chance for close monitoring, earlier diagnosis and preventative management. Our knowledge of cancer genetics is now increasingly shaping the way we treat the disease, by allowing us to offer more intensive treatment, or even different drugs altogether, for people who have inherited cancer genes.”

Dr Julie Sharp, Senior Science Information Manager at Cancer Research UK, said: “This study shows that doctors need to consider treating men with prostate cancer and a faulty BRCA2 gene much sooner than they currently do, rather than waiting to see how the disease develops. We knew that men who inherit a faulty BRCA2 gene are at a greater risk of developing prostate cancer but this is the largest study to show that the faulty gene also makes the disease more likely to develop quickly and spread.”

Professor David Cunningham, Director of Clinical Research at The Royal Marsden, said: “Studies such as this are very important in helping us to determine how we personalise the treatment of prostate cancer patients at The Royal Marsden. This detailed understanding of men who have the BRCA1/2 gene mutations and the influence of these mutations on the progress of the prostatic cancer will mean that they will receive the tailored treatment they need quickly, and ultimately this will benefit our patients and patient outcomes.”

Prostate Cancer in the UK

Around 40,800 men are diagnosed with prostate cancer in the UK each year and one Briton dies every hour from the disease.

BRCA1 / 2 mutations were originally identified in breast cancer patients and can increase the risk of developing breast and ovarian as well as prostate cancers. BRCA2 and BRCA1 mutations are present in 1.2 per cent and 0.44 per cent of prostate cancer cases, respectively. A man with a BRCA2 mutation has a 8.6-fold increased risk of developing prostate cancer, while a BRCA1 mutation gives a 3.4-fold increased risk.

Men with a significant family history of breast and /or ovarian cancer in addition to prostate cancer can be offered BRCA1/2 testing at diagnosis, however it is not routinely offered to all patients diagnosed with prostate cancer in the UK. The research team believe it should be offered to all under-65s with prostate cancer, based on a previous study that found one in 100 of these men carries the faulty gene, as it may help identify men who could benefit from new types of targeted treatment. This will, however, only become possible universally when the test is cheaper and quicker to run, as new genetic technologies are brought into mainstream cancer care.


Source: The Institute of Cancer Research (ICR)