Dr. Jeffrey Swensen is the Associate Director of Molecular Genetics at Caris Life Sciences in Phoenix, Arizona.
Prostatepedia spoke with him recently about prostate cancer screening for men with BRCA2 mutations. (See Prostatepedia March 2017 for a discussion with Dr. Swensen about molecular profiling for prostate cancer.)
Should a man with a BRCA2 inherited mutation be screened earlier for prostate cancer?
Dr. Swensen: Carrying a pathogenic BRCA2 mutation increases the risk for prostate cancer, and that cancer is more likely to be aggressive and earlier onset. There are recommendations that suggest male BRCA2 carriers should be screened more aggressively for prostate cancer. Male BRCA2 and, to a lesser extent, BRCA1 mutation carriers are also at increased risk for other cancers, including male breast cancer and pancreatic cancer. Screening male BRCA2 mutation carriers for breast
cancer is generally recommended; screening for pancreatic cancer is generally not unless there is a family history of that cancer.
Would it make sense to offer prostate cancer screening to male children of a prostate cancer patient earlier?
Dr. Swensen: No. A man with a BRCA2 mutation tends to get prostate cancer at an earlier age than the standard person in the population. But it’s generally not really early onset.
A female with a BRCA1 or BRCA2 mutation is at higher risk for breast and ovarian cancer and the onset can be at a considerably younger age. However, screening is typically not performed on these women until they’re adults.
Male BRCA2 mutation carriers are at increased risk for cancers, but the risk is not the same magnitude as the risk for the women. The lifetime risk has been estimated to be around 20% for prostate cancer in a male BRCA2 mutation carrier; a female carrier of a BRCA2 or BRCA1 mutation has a lifetime risk of breast cancer that may be up to 80%.
A female BRCA1 or BRCA2 mutation carrier will be counseled and followed extensively. After they reach a certain age and have had children, they can have their breasts and ovaries removed to significantly reduce their risk. That is what Angelina Jolie did.
Are there any other mutations that are significant for prostate cancer?
Dr. Swensen: There is a mutation in another gene that has been shown to be a risk factor for prostate cancer: G84E in the HOXB13 gene.
This mutation is carried by about 0.5% of individuals of European ancestry. It is not a high-risk mutation. Male carriers have a two to threefold increased risk of prostate cancer. The mutation is not known to be therapeutically significant.
Is that mutation associated with an increased risk of getting prostate cancer or of getting aggressive prostate cancer?
Dr. Swensen: That has still not been clearly defined.
Does it make sense to offer prostate cancer screening earlier to men with the G84E germline mutation in HOXB13?
Dr. Swensen: It is one of many genetic factors that will influence an individual’s risk of cancer. At this time, though, screening is not warranted.