A new study just published on line in the Journal of Clinical Oncology had confirmed that “BRCA1/2 mutations confer a more aggressive [prostate cancer] phenotype with a higher probability of nodal involvement and distant metastasis.” This is not a surprising finding, but it does have real implications for men with a family history of BRCA1/2 mutations.
According to the paper by Eeles et al. (and the related commentary on the BBC News web site, posted late on Monday this week), the study was designed to look for tumor features and clinical outcomes among > 2,000 patients diagnosed with prostate cancer, to identify the patients carrying either BRCA1 or BRCA2 mutations, and to tease out correlations between the presence of BRCA1/2 mutations, other known prognostic factors, and patient outcomes over time.
Here is what Eeles and her colleagues report:
- Data from 2,019 patients with prostate cancer were assessed.
- 18/2,019 patients (0.8 percent) were BRCA1 positive.
- 61/2,019 patients (3.0 percent) were BRCA2 positive.
- 1,940/2,019 patients (96 percent) were BRCA1/2 negative.
- Compared to the non-carriers of these genes, patients with BRCA1/2 mutations were at significantly higher risk for
- A Gleason score of 8, 9, or 10 (P = 0.00003)
- Stage T3 or T4 disease (P = 0.03)
- Positive regional lymph nodes (P = 0.00005)
- Metastatic disease at time of diagnosis (P = 0.005)
- Data on prostate cancer-specific survival (PCSS) of all 2,019 patients showed that
- Average PCSS among BRCA1/2-negative patients was 15.7 years
- Average PCSS among BRCA1/2-positive patients was 8.1 years
- Data on survival of the patients initially diagnosed with localized disease showed that
- 92 percent of BRCA1/2-negative patients had a 5-year PCSS.
- 82 percent of BRCA1/2-positive patients had a 5-year PCSS.
- 93 percent of BRCA1/2-negative patients had a 5-year metastasis-free survival (MFS).
- 77 percent of BRCA1/2-positive patients had a 5-year MFS.
The authors note also, “Subgroup analyses confirmed the poor outcomes in BRCA2 patients, whereas the role of BRCA1 was not well defined due to the limited size and follow-up in this subgroup.”
Quoted in the story on the BBC News web site, Dr. Eeles states 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.
In other words, BRCA2-positive patients who are diagnosed with prostate cancer should be treated early and aggressively because their tumor is more likely to spread than the tumors of men who are BRCA2 negative. Active monitoring of any type is probably not a good options for BRCA2-positive patients.
As we indicated above, this is not exactly as surprise. Also commenting on this research, Dr. Julie Sharp of Cancer Research UK is quoted as follows:
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.
The presence of the BRCA2 gene is associated specifically with high risk for hereditary forms of breast and ovarian cancers in women as well as prostate cancer in men. The most recent estimates suggest that about 1 percent of all men diagnosed with prostate cancer have hereditary BRCA2-positive disease (even though 3 percent of the men in this study were BRCA2 positive).
Filed under: Diagnosis, Management, Risk, Treatment | Tagged: BRCA1, BRCA2, hereditary, mortality, risk, survival |
THE "NEW" PROSTATE CANCER INFOLINK 
Hmmm … I have never heard of this. Are men diagnosed with prostate cancer tested for the BRCA2 gene mutation in real world practice? I remember reading in Francis Collin’s book on genetic medicine/diagnosis (a good read, by the way) that Sergey Brin (founder of Google) had a perfectly healthy prostate removed because some genetic marker indicated he was at a higher risk of prostate cancer. I can’t remember what the genetic marker was. (In my thinking, this was nutty … but who am I to disagree with the founder of Google?) I also have personally known a woman who had her perfectly healthy breasts removed due to the presence of the BRCA2 mutation along with a rather terrifying family history of deaths from breast cancer.
Are there any known correlations between BRCA status and PSA?
Dear Doug:
Men commonly learn that they are potential BRCA2 carriers because of a family history of breast or ovarian cancer among their grandmothers, their mothers, and their sisters. Any man with a family history of BRCA2 positivity would be wise to know whether he is a carrier. It comes with potentially devastating consequences. I don’t know if that’s why Sergey Brin had his prostate removed, but it may well be.
The costs associated with testing every man diagnosed with prostate cancer for BRCA2 would be high and only 1% of men carry the BRCA2 gene. (See today’s other story about an upcoming Supreme Court case on the patentability of human genes. Myriad Genetics holds a patent that has given them a monopoly on testing for the BRCA1 and BRCA2 genes.)
There is an growing literature on this topic. A lot of the relevant research has been done in Australia, where the prevalence of the BRCA1/2 genes appears to be higher than it is here in the USA.
I just sent out for a test kit from 23andMe to have my personal DNA tested. However, they indicated that there are hundreds of BRCA1/BRCA2 genes and they only covered three? The test itself is inexpensive ($99), and I don’t know if their BRCA1/BRCA2 tests are specific to prostate cancer or not. Since I am on active surveillance, I am always looking out for tests that will help me determine if my prostate cancer is indolent or aggressive.
Please see their caution below.
“Please remember that the BRCA mutations covered by this report are only three of hundreds in the BRCA1 and BRCA2 genes that can cause cancer. Their absence does not rule out the possibility that you may have another cancer-causing variation in one of those genes.”
Dear Mike:
The BRCA1 and BRCA2 tests offered by 23andMe are very different from the tests offered by Myriad Laboratories, which have been carefully correlated with the actual risk for cancer. I don’t have any reason to believe that the tests offered by 23andMe provide any level of clinical significance whatsoever in this situation.
For those interested, here is a link to a recent article about (PARP) inhibitors for the treatment of advanced germline BRCA2 mutant prostate cancer.
Just went back to the 23andme website and read about their BRCA1/BRCA2 tests and realized they are specifically for breast cancer. Oh well, for $99 I will learn a little bit more about myself, good or bad, I do not know.