PARP Inhibitors in Prostate Cancer - Episode 9

BRCA1/2 in Metastatic Prostate Cancer

An expert considers the role of BRCA1/2 mutations in metastatic prostate cancer.

Matthew Fowler: What is the role of BRCA1/2 in prostate cancer? What percentage of men with prostate cancer harbor a BRCA1 or BRCA2 mutation?

Alicia Morgans, MD, MPH: BRCA2 is the most common. BRCA1 is much less common. When we think about all the DNA-repair defect alterations that we can target with PARP inhibitors, it’s about 11.8% of men with metastatic cancer. About 10% of these might be BRCA2, and a much smaller percentage might be BRCA1. But BRCA2 is the most common in men with prostate cancer. We’ll often see that these men have an aunt with breast cancer or their mother had ovarian cancer, in addition to male family members who have a history of prostate cancer. As we think about these heritable mutations, it’s important to recognize that they can be associated with not just prostate cancer but cancer syndromes outside prostate cancer, including breast and ovarian cancer.

The other important thing to remember is that the guidelines suggest for germline testing in particular that we don’t do only germline testing in men who are younger at the time of diagnosis or who have family members who have a history of these cancers that may be involved in these syndromes. Because what was so fascinating is that the 11.8% of men with metastatic prostate cancer who have these germline heritable mutations didn’t have a higher rate if they had a family member who had a history of one of these cancers. It can be a clue that we may be ready to see one of these alterations in the germline of one of our patients, but it’s not a clear and definite association that would necessarily guide our germline testing.

This transcript has been edited for clarity.