What Prostate Cancer Has To Do With Breast Cancer…

What Prostate Cancer Has To Do With Breast Cancer…

Most people who know about BRCA genes think about them in relation to breast cancer. The name given to the gene in fact—BRCA–stands for BReast CAncer associated gene. People with an inherited mutation in their BRCA1 or BRCA2 genes have a lifetime increased risk of developing breast cancer. But did you know that mutations in BRCA genes are also linked to men’s prostate cancer risk?

Recent research has shown that men with an inherited BRCA gene mutation (as well as a few other gene mutations) have an increased risk of prostate cancer and may also be at risk for more aggressive forms of prostate cancer.1 In men with BRCA gene mutations, prostate cancer tends to develop at a younger age and may also be of the type that is more aggressive and more likely to become metastatic.

What are BRCA genes?

Both men and women have BRCA1 and BRCA2 genes. The normal function of these genes is to repair cell damage and keep our cells growing normally. In fact, BRCA genes are often called DNA-repair genes. When these genes have an abnormal structure (DNA) or become mutated they no longer function correctly.

This defect in the DNA repair ability of these BRCA gene mutations is associated with increased risk of breast, ovarian, prostate, and other cancers.2 Some of these genetic mutations can be inherited, thus increasing the risk of cancers within a family from one generation to the next. BRCA gene mutations can be inherited from one’s mother or father.

Overall, about 5-10 percent of men with prostate cancer have a hereditary factor implicated including a BRCA gene mutation, although not all of the genetic mutations that cause prostate cancer are known.2 The hereditary risk of prostate cancer increases with the number of relatives with prostate cancer, but also the number of relatives with breast and ovarian cancers as well.

BRCA gene mutations increase cancer risk

Research has demonstrated strong links between men with prostate cancer and mutations in their BRCA1, BRCA2 and other genes. A groundbreaking study published in the New England Journal of Medicine in 2016 found BRCA mutations in 11.8% of men with metastatic prostate cancer, compared with 2.7% of men without a known cancer diagnosis.3

Men with BRCA gene mutations have a 15-25% lifetime risk for prostate cancer, which is higher than the average risk for men within the same age groupings. Men with an abnormal BRCA1 gene have a slightly higher risk of prostate cancer. Men with an abnormal BRCA2 gene are 7 times more likely than men without the abnormal gene to develop prostate cancer.3

Other cancer risks, such as skin cancer or colorectal cancer, also may be higher in men with abnormal BRCA1 or BRCA2 genes.

As stated above, these studies also suggest that men with prostate cancer who have these BRCA variants are more likely to have aggressive disease. In these studies, men with BRCA mutations tend to have higher Gleason score, higher PSA level at diagnosis, and higher tumor stage and/or grade at diagnosis.

Updated screening guidelines

In February 2018, the National Comprehensive Cancer Network (NCCN) updated its guidelines to recommend expanded genetic screening for prostate cancer. According to NCCN, men with prostate cancer that has spread outside the prostate gland into nearby tissue regionally and men with metastatic disease, regardless of age, should have genetic testing performed by a specialist.4

NCCN also recommends beginning screening for prostate cancer (PSA and DRE) at an earlier age (age 45) for men who have known BRCA mutations or inherited risk.

Men who have prostate cancer should talk to their doctor about tests, including genetic testing, that can be used to determine if prostate cancer is an aggressive type that may require additional treatment or monitoring. Your healthcare provider may refer you to a genetic counseling program so that you can make an informed decision about the value of genetic testing for your situation.

If prostate cancer, breast cancer, or ovarian cancer runs in your family, consulting with a genetics specialist can help you determine your risk and management options.

Treatment implications? Further research needed

Clinical trials are currently being conducted to determine what treatments may be most effective for men with BRCA mutations that have hormone-resistant prostate cancer. These trials include platinum-based chemotherapy and poly-ADP ribose polymerase (PARP) inhibitors for men with BRCA mutations and metastatic prostate cancer.3

The PARP inhibitor, olaparib, is currently FDA approved for specific ovarian and metastatic breast cancers in women with BRCA mutations and has Breakthrough Therapy designation by FDA for metastatic hormone-resistant prostate cancer.

[Editorial note: Men with a BRCA mutation are also at risk for breast cancer and NCCN recommends men’s clinical breast exam starting at age 35 for these men]

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