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The Role of Genetic Testing in Advanced Prostate Cancer

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Published on August 5, 2016

With 11 percent or more of advanced prostate cancer patients carrying inherited mutations like BRCA1 and BRCA2, should men be tested for these genetic markers?  From ASCO 2016, Dr. Tomasz Beer moderates a roundtable discussion on genetic testing with advanced prostate cancer experts, Dr. Russell Szmulewitz, Dr. Emmanuel Antonarakis and patient advocate Joel Nowak.  The panel shares their thoughts about genetic counseling and testing now available for both inheritable (germline) and non-inheritable (somative) mutations. 

Sponsored by the Patient Empowerment Network through educational grants from Sanofi Oncology and Astellas Pharma Inc.

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Transcript | The Role of Genetic Testing in Advanced Prostate Cancer

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you. 

Dr. Beer:

A paper from Peter Nelson, presented at this meeting, reported that more than 11 percent of men with advanced prostate cancer carry inherited mutations that are associated with a defect in these DNA repair pathways. The more famous of these are the so-called BRCA genes, BRCA1 and BRCA2. Many people are aware of these genes. They are associated with an increased risk of breast and ovarian cancer. 11 percent, that’s a surprise. Should we be offering testing for these inherited defects to our patients with advanced prostate cancer, and what does that mean for their families? 

Dr. Antonarakis:                

I think we need to make a distinction here and maybe also educate the audience. When we’re talking about these mutations for men, there [are] two different types. The first type is the one that you’re born with. We call that germline; that’s just the jargon. 

It means it’s the one you’re inherited with, and you can pass on to your kids in your family. The second type of mutation is called somatic. The somatic mutations are only found within the tumor but not necessarily the ones that you were born with, and you can’t really inherit and pass on a somatic mutation. So here what we’re talking about [are] germline mutations, these mutations that you are born with, that you can also pass off to your offspring. And we thought that these mutations existed in 2 to 3 percent of men. Now we think it’s remarkably higher, maybe up to 11 or 12 percent.

And yes, Tom, I do think that’s a bit of a game changer, because now it’s not really as rare as we once thought. And as was mentioned by Russell, we now may have a therapy, these PARP inhibitors such as olaparib (Lynparza), which could provide clinical benefits to those patients. So I think there’s a lot of hope there. But there are also implications for family counseling. If a man has one of these mutations, let’s say BRCA2, then that person’s sister or daughter may have to be screened for breast cancer or ovarian cancer.

So there are other implications beyond the prostate cancer diagnosis itself.

Joel Nowak:       

And I also think there’s an implication for children of men who are diagnosed with prostate cancer and grandchildren and so forth and so on. We’ve known that there’s some sort of genetic relationship in a small number of men. But understanding how much larger it is than we actually thought really means that it’s more important for anyone who has had prostate cancer or their family—first-degree relative has had prostate cancer, that they really do make sure they speak to their doctor about finding out where their PSA is, doing some pre-work and also looking at ways they may be able to do to help prevent the development of the disease. 

And I also want to thank you so much for your excellent explanation of germline; for a lot of people who don’t understand that. 

Dr. Beer:                

I do want to highlight for the audience that this high rate of inherited mutations is being foundin line with metastatic advanced prostate cancer. 

We think there’s a distinction between localized and advanced, and so I'm not sure that all men with prostate cancer need to be concerned that they have a high risk of having these mutations. But those men who have metastatic disease probably should be talking to their doctors about that. Russ, do you have any additional on this?

Dr. Szmulewitz:

I would just add that when we’re talking about testing for these genes, that the germline, the inherited risk, we can do with a blood test. The mutations that are somatic that you get perhaps in a tumor over time, they have to be assayed; you actually have to test the tumor material. What papers have now shown us is that the rate of those aberrations, those abnormalities, might be as high as 25 or 30 percent in advanced prostate cancer tumors. So in my practice, if we’re looking at in the upcoming months how you might triage this and how you might proceed with a patient in your office, we might start with family counseling in genetic risk and a blood test.

And if they have a mutation there, that gives us hope that this medication might help. Otherwise, we might be doing more biopsies sequentially as the disease progresses to look for some of these mutations.

Dr. Beer:                

That’s a tremendous change, I think. For patients out there I would say we’re working on it, trying to sort this out. We haven’t implemented biopsies for everybody of metastatic disease in practices yet, but I think we’re going to either do that or look to assays that try to detect circulating tumor DNA and perhaps get around the need for a biopsy.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you. 

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