First Man Has Prostatectomy Because of BRCA Gene Mutation

Zosia Chustecka

May 21, 2013

UPDATED May 21, 2013 — The first man has undergone prostatectomy after finding that out that he carries the BRCA2 gene mutation.

BRCA gene mutations increase the risk for a number of cancers, including prostate cancer. They were in the news last week after superstar Angelina Jolie announced that she had a prophylactic mastectomy to avoid breast cancer.

Hot on the heels of that extensive media coverage, news of the first prophylactic prostatectomy because of the genetic mutation made the front page of the Sunday Times.

The surgery was performed by Roger Kirby, MD, director of the Prostate Cancer Center in London, United Kingdom, an eminent prostate cancer specialist who has performed more than 2000 prostatectomies. Ironically, he himself recently underwent radical prostatectomy after prostate cancer was found.

The man who underwent surgery was participating in a clinical trial, conducted by the Institute of Cancer Research (ICR), that involved more than 20,000 men. Previous results from this trial have shown that a man with a BRCA2 mutation has an 8.6-fold increased risk of developing prostate cancer, and with a BRCA1 mutation has a 3.4-fold increased risk. Just weeks ago, the ICR researchers reported that prostate cancer in men with the BRCA2 mutation is more aggressive and more likely to be fatal (J Clin Oncol. 2013;31:1748-1757).

"Knowing you are a carrier is like having the sword of Damocles hanging over you," Dr. Kirby said in an interview with the Sunday Times. "You are living in a state of constant fear. I am sure more male BRCA carriers will follow suit."

The man who underwent the surgery is described as a 53-years-old businessman from London who is married with children and has several family members who have had breast or prostate cancer. When he found out he was carrying the BRCA2 mutation, he asked to have his prostate removed.

Initially, the ICR researchers were reluctant, the newspaper reports, because there was no indication of a problem, either from prostate-specific antigen tests or from a magnetic resonance imaging scan. However, a biopsy showed microscopic malignant changes.

Even then, however, Dr. Kirby said he would not have operated if the man had not been identified as a carrierof the BRCA2 gene mutation.

"The relatively low level of cancerous cells we found in this man's prostate before the operation should, these days, not prompt immediate surgery to remove the gland, but given what we now know about the nature of BRCA2, it was definitely the right thing to do for this patient," he told the newspaper.

BRCA2 Prostate Cancer Aggressive and Lethal

When the results of the ICR study showing that prostate cancer in men with BRCA2 mutations is both aggressive and lethal were first published, senior author Ros Eeles, MBBS, PhD, professor of oncogenetics at the ICR and honorary consultant in clinical oncology at The Royal Marsden NHS Foundation Trust in Surrey, United Kingdom, said that "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," she said in an ICR statement.

The ICR research team examined the medical records of 61 carriers of the BRCA2 mutation, 18 carriers of the BRCA1 mutation, and 1940 noncarriers.

They found that BRCA1/2 mutation carriers were more likely than noncarriers to be diagnosed with advanced-stage prostate cancer (37% vs 28%) or cancer that had already spread (18% vs 9%). For those whose cancers had not spread past the prostate at diagnosis, more carriers than noncarriers had metastatic disease within 5 years (23% vs 7%).

Patients with BRCA2 mutations were also significantly less likely to survive the cancer; survival was significantly shorter in carriers of the mutation than noncarriers (6.5 vs 12.9 years). The researchers conclude 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 (10.5 years), but it was not significantly different from noncarriers.

Alan Ashworth, PhD, chief executive of ICR, explained that testing for the BRCA2 gene has "offered families with an inherited risk for 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."

Julie Sharp, MD, senior science information manager at Cancer Research UK, noted that "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've known that men who inherit a faulty BRCA2 gene are at 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."

Decision Based on Emotion, Not Data

"The issue of performing a so-called prophylactic prostatectomy because the man is a carrier of the BRCA gene raises many complexities," said Marc Garnick, MD, clinical professor of medicine at the Beth Israel Deaconess Medical Center in Boston, Massachusetts. Dr. Garnick, who is editor-in-chief of the Harvard Annual Report on Prostate Diseases, was approached for comment by Medscape Medical News.

According to the news report, this man "had actual evidence of prostate cancer, as determined by the presence of malignant cells in his prostate gland.... This is not necessarily comparable to a woman without any evidence of cancer — just a heightened risk of developing cancer — selecting prophylactic mastectomy because she is a BRCA gene carrier," Dr. Garnick pointed out.

This patient is totally representative of the population of men who would have undergone radical prostatectomy in the past, he explained. "However, recent controversies about the harm resulting from these procedures performed on men with otherwise only microscopic cancers has brought this practice into sharper focus."

The recent ICR results suggesting that male BRCA carriers who have prostate cancer have more aggressive cancers is "of interest, but preliminary, and worthy of additional study," Dr. Garnick noted.

Prophylactic radical based predominantly on emotions, not data. Dr. Marc Garnick

"The real unanswered question relates to whether our current interventions, if applied to this group of men with aggressive cancers, either with or without BRCA mutations, will ultimately have a positive impact on the course of the disease. Pessimistically, most of the level 1 data suggest this not the case, but the potential association between BRCA with more aggressive prostate cancers provides a fertile ground for appropriately conducted clinical research to help answer the question for the patients we serve," Dr. Garnick explained.

"Currently, a man's decision to undergo a prophylactic radical prostatectomy because he is carrying the BRCA gene is based predominantly on emotions, not data. Medical science is charged with determining if this is ultimately the right thing to do, and only appropriately conducted clinical research can answer this question," he said.


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