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For decades, doctors have been able to easily identify women who have a higher risk of developing breast cancer because of their genes. Testing for mutations in the BRCA1 or BRCA2 genes can help women learn if they are more likely to develop breast or ovarian cancer, which can lead them to get screened more regularly and take advantage of effective treatments.
Now researchers have recognized a similar set of genes that can distinguish aggressive prostate cancer. In a report published in the New England Journal of Medicine, scientists say that a panel of 20 genes can distinguish the more common localized prostate cancer that grows slowly and rarely spreads from the more aggressive type that can spread quickly.
In a study involving 692 men with advanced prostate cancer that had spread, researchers led by Dr. Peter Nelson at the Fred Hutchinson Cancer Research Center looked at 20 genes known to be involved in DNA repair. These genes are highly associated with prostate cancer risk. If Nelson and his team found more mutations in these genes among men with metastatic prostate cancer, then that would suggest that these genes are good predictors of more aggressive cancer.
The rate of mutations in these genes was nearly 12% among these men, compared to about 5% among men with slower growing, localized prostate cancer.
“This study has a relatively simple message: those with advanced prostate cancer should consider genetic testing both to help their own treatment and also so family members can take preventive action,” says Dr. Kenneth Offit, chief of clinical genetics at Memorial Sloan Kettering Cancer Center (MSKCC) and a co-author of the study.
Some anti-cancer drugs target some of the mutations the researchers identified, which means that genetic testing could help these men start the most effective treatments more quickly. Because the mutations are in inherited cells, and not just the tumor cells, the results can also be helpful to other family members who might share some of the same mutations.
Offit says that in his clinic, where the panel is already being used in research studies, he was able to test the daughter of a man with metastatic prostate cancer and learn that she carried mutations that put her at higher risk for ovarian cancer. Without the test, she might not have been identified as a person at higher risk of that cancer.
While men with the more aggressive form of the cancer make up about 5% of the 180,000 to 200,000 cases of prostate cancer in the U.S. each year, and only 12% will have these mutations, that population is still at considerably higher risk of developing advanced disease. And because there are effective treatments that address their mutations, the researchers believe that doctors should be offering the genetic test—and that insurers should be paying for them—for men with advanced prostate cancer.
The findings also hint that in coming years, it may be possible to use the panel not just among men with advanced disease but to distinguish between men who develop the slower growing type of prostate cancer from the more aggressive type. That would help them to know if they need more regular screening and treatment, or whether they can take advantage of so-called active surveillance, in which doctors monitor the progress of the cancer but don’t take any immediate action in treating it because it’s so slow-growing. “If you are a man found to have one of these mutations, then active surveillance would not be in your best interest,” says Nelson. “Even though clinically you might appear to be low risk, under the microscope your cells are behaving much more adversely.”
It will take more research to establish which men should be getting such testing; for now, the study found that looking at family history alone wouldn’t help since the men with these mutations didn’t seem to have more family members with cancer. It’s likely that once men are diagnosed, “this information will be helpful in screening patients and determining which are at higher risk,” says Dr. Michael Walsh, from the departments of medicine and pediatrics at MSKCC and another co-author of the study.
For now, says Nelson and his team, the test should be part of any man’s care if he is diagnosed with advanced prostate cancer. “We’re definitely advocating for all men with metastatic prostate cancer to have this testing,” he says. “The frequency of 12% is a reasonably high enough hit rate to support that kind of testing.” Whether insurance companies will cover the cost of the testing is another issue, but results like these may help to change national guidelines to include this test for these men, and that in turn may help insurers decide to pay for it.
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