By Will Boggs MD
NEW YORK (Reuters Health) - 4/10/2019
Men with mutations in BRCA2 have an increased risk of prostate cancer and should be offered prostate-specific antigen (PSA) screening, according to the team behind the IMPACT study.
Recent findings (https://bit.ly/2kL3BX1) from the ongoing EMBRACE study demonstrated an increased risk of prostate cancer in men with BRCA mutations, with a higher risk and more aggressive disease in those with BRCA2 mutations, as reported by Reuters Health.
In a paper online September 16 in European Urology, Dr. Rosalind A. Eeles of the Institute of Cancer Research, in London, and colleagues report interim findings from IMPACT on the utility of PSA screening and other data after three years of screening, stratified by BRCA status.
The study included 919 BRCA1 carriers, 709 BRCA1 noncarriers, 902 BRCA2 carriers, and 497 BRCA2 noncarriers (median enrollment age, 54 years).
At baseline, 7.7% of nearly 3,000 participants tested had a PSA >3.0 ng/mL and 2.4% were diagnosed with cancer.
After four PSA screens, cancer was diagnosed in 5.2% of BRCA2 carriers and 3.0% of BRCA2 noncarriers and in 3.4% of BRCA1 carriers and 2.7% of BRCA1 noncarriers.
The cancer incidence rate per 1,000 person-years was significantly higher among BRCA2 carriers than among noncarriers (19 vs. 12, P=0.031), but did not differ significantly between BRCA1 carriers and noncarriers (14 vs. 11, respectively, P=0.3).
The positive predictive value (PPV) of prostate biopsy did not differ significantly between BRCA2 carriers and noncarriers or between BRCA1 carriers and noncarriers.
The PPV of PSA >3.0 ng/mL was significantly greater in BRCA2 carriers than noncarriers (31% vs. 18%, P=0.025), but not between BRCA1 carriers and noncarriers (23% vs. 15%, P=0.13).
The median age at prostate-cancer diagnosis was significantly younger in BRCA2 carriers (61 years) than in BRCA2 noncarriers (64 years) but did not differ between BRCA1 carriers and noncarriers.
Most BRCA2 carriers (37/48, 77%) diagnosed with prostate cancer had intermediate- or high-risk disease, significantly more than among BRCA2 noncarriers diagnosed with prostate cancer (6/15, 40%). The rate of clinically significant disease rates, however, did not differ between BRCA1 carriers and noncarriers.
Based on these findings, the authors conclude that "systematic PSA screening is indicated for men with BRCA2 mutation. Further follow-up is required to assess the role of screening in BRCA1 mutation carriers."
Dr. Tommy Nyberg of the University of Cambridge, in the U.K., lead author of the recent EMBRACE report, told Reuters Health by email, "The BRCA2 results of the IMPACT and EMBRACE studies seem complementary, and consistently suggest that men with BRCA2 mutations are at high lifetime risks of prostate cancer and that targeting this group of men for regular PSA tests would result in the detection of a high proportion of aggressive cancers."
"I hope that these results will be useful both to the clinician who meets a male BRCA2 carrier, and to inform the debate on targeted prostate cancer screening of high-risk groups," said Dr. Nyberg, who was not involved in the IMPACT study.
Dr. David Margel of Rabin Medical Center, in Petah Tikva, Israel, who recently reviewed the screening and treatment of prostate cancer among carriers of BRCA mutations, told Reuters Health by email, "The main point which is implicit from this manuscript is that men with BRCA2 are at high risk for prostate cancer and should be screened."
It remains to be seen "whether a real difference exists between BRCA1 and BRCA2 mutations," he said. "In Israel there is a predominance among male BRCA carriers of the 3 Jewish founder mutations. And in my experience men with a 185delAG, which is a BRCA1 mutation, have the same risk of prostate cancer as BRCA2."
"The most important endpoints for any cancer screening protocol are cancer-specific and overall mortality," Dr. Margel added. "It would be interesting to see in the future if the screening affects not only cancer diagnosis, but also overall and cancer-specific mortality."
Dr. Heather Cheng of Fred Hutchinson Cancer Research Center and the University of Washington, in Seattle, who also studies prostate-cancer screening, told Reuters Health by email, "It is important for men and their doctors to know that if they carry a BRCA2 mutations, there is an increased risk of prostate cancer and that screening for prostate cancer is warranted. Men with inherited BRCA2 mutations should be counseled and managed differently with respect to prostate cancer screening than average-risk men."
"When considering the risk of prostate cancer, it is important to consider the family history of other cancers, including breast, ovary, pancreas, melanoma, (and) leukemias," she said. "If there are multiple relatives with cancer, especially diagnosed at younger ages (e.g., younger than 50s), genetic counseling referral should be considered. Moreover, knowing about a familial cancer risk may help in tailoring cancer screening strategies for that person, but may also provide valuable information for their relatives."
Dr. Eeles did not respond to a request for comments.
Eur Urol 2019.
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