BRCA yourself

Cancer

22nd November 2014

Since the announcement by Angelina Jolie of her preventative breast cancer surgery last year, newspapers have been awash with further reports and case studies of women opting for similar radical surgery. Jolie revealed earlier this year that she will have further preventative surgery — one assumes the removal of her ovaries — to reduce her familial cancer
risks even more.

The follow-up stories and features are ubiquitous: countless women are having to make the same life-changing decisions. But where does this leave their male relatives? Are we soon to witness the advent of male preventative cancer surgery?

When we talk about familial cancer genes, BRCA is probably the best-known both in terms of public understanding and also medical knowledge. Cancer and genetics is a very new area of medical science; we are only just beginning to understand these associations.

There are two BRCA genes, known as BRCA1 and BRCA2. We know that in women these confer a risk of breast and ovarian cancer. More recent research has looked at the effects of these genes on men.

What is coming out now from the most recent studies is that BRCA2 genes particularly seem to be associated with a much higher chance of prostate cancer. At this stage the Institute of Cancer Research has published data showing a definite link, and future research into the genetics will allow the exact risk to be quantified, as it has been for breast cancer. Current estimates appear to show the risk of prostate cancer would be doubled if a man were carrying BRCA2.

But unfortunately the bad news doesn’t seem to end there: BRCA2 appears to be associated with a much worse form of the disease as well. Prostate cancer in the majority of cases is a slow-growing cancer that may not require treatment other than observation: doctors usually take a conservative approach, known as ‘watch and wait’, which often circumvents the need for surgery altogether. This is the type of prostate cancer men get in their seventies or eighties. The BRCA2 gene, however, has been linked with the much more aggressive form which affects younger men and spreads much faster. This requires radical surgery and carries a far more sinister prognosis.

Last year a British man became the first in the UK to undergo preventative prostate surgery to minimise his risk of cancer. This was a landmark situation, the first of its kind. He already had the very earliest of signs of prostate cancer, which would not have normally warranted surgery, but rather a more measured, conservative approach. However, as he was involved in a research trial and was known to be BRCA2 positive, the team involved agreed to the radical surgery because he had both the gene and the first signs of cancer.

There are major downsides to prostate surgery when compared for example with preventative mastectomy. The benefits of surgery must be weighed up against the risks, and in the case of preventative prostate surgery — a prostatectomy — there are long-term implications that have a significant effect on a man’s quality of life. Impotence, ejaculation problems and incontinence are common sequelae of the operation, so it would only ever be a reasonable option where the risk was proven to be exceedingly high or cancer was already present.

BRCA-Stats

Knowing your genes and being able to quantify the risks exactly will be key to the future of this type of surgery. This is no small undertaking for a man in his forties or fifties: the life-changing complications could only be contemplated in the face of confirmed genetic risk.

Researchers are hoping to shed more light on the BRCA prostate risks from trials currently under way. The IMPACT trial is an international trial looking at prostate cancer in those with known BRCA genes. The trial started recruiting in 2005 and so far is observing more than 3,000 men both with and without the cancer-causing genes. The aim is to establish how much BRCA alters the chances of aggressive disease and death from prostate cancer. It is also looking at PSA blood testing as a screening tool for high-risk men. PSA is an enzyme which we know is elevated in men with prostate cancer. However, screening for it is a poor test in a healthy population as it also rises in a whole host of non-cancerous conditions. But it is possible that in those men with known BRCA genes, it is a useful tool for targeted screening leading to earlier diagnosis and improved survival. It may also lead to preventative surgery in those willing to risk the consequences.

Male preventative cancer surgery is on the horizon but the path is still unclear. Trial data is certainly opening up this area and will hopefully provide the answers to a very difficult conundrum. But it is easy to imagine the newspaper headlines in the not-too-distant future, when the first male celebrity reveals he has undertaken this radical step.