PracticeUpdate: Haematology & Oncology | Vol 1.No.3 - 2016

FEATURE ARTICLE

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Genetic testing in patients with relevant

family history in prostate cancer Interview with Oliver Sartor, MD

PracticeUpdate ’s Dr Farzanna Haffizulla speaks with Dr Oliver Sartor, Laborde Professor of Cancer Research in the Medicine and Urology Departments of the Tulane School of Medicine in New Orleans, about genetic testing for BRCA1 and BRCA 2 mutation genes, and its implications, for men with prostate cancer.

Dr Haffizulla: Let us focus our atten- tion on prostate cancer and its as- sociation with BRCA1 and BRCA2 genes. Can you share your expertise and perspective? Dr Sartor: It is really quite interesting. This is a new insight many people are not aware of. BRCA1 and BRCA2 are identified with breast cancer and ovarian cancer, and everybody is familiar with that, but now there is an appreciation that probably about 10% of men with advanced pros- tate cancer have DNA-repair gene defects, and BRCA2 is the most common. BRCA1 and BRCA2 are the majority, but also there are some ATM and other genes as well.

Dr Haffizulla: Does it have a correla- tion with the aggressiveness of the tumour itself? Dr Sartor: It does. In fact, there are some beautiful studies coming out of the UK in particular that have looked at these people with germline mutations and how they present. They present with more aggressive disease, more advanced disease and, of course, a lot of the men are not aware that prostate cancer might be related to germline risk; so it’s an important new finding. Dr Haffizulla: Do you recommend then, knowing that there is more aggressiveness of the tumour itself with these particular associations, testing for that concurrently with PSA? Dr Sartor: Well, we are doing it a lit- tle bit differently simply because of funding restrictions but we’re very, very compulsive about our fam- ily histories, and we have to follow guidelines. We are using the NCCN guidelines but if we find that there are guidelines that are compatible with family history (somebody has a brother with prostate cancer that’s aggressive, or a sister with ovarian

Dr Haffizulla: This new information just unearthed so much more that we need to not only research but cover. All the ethical implications on the therapeutic landscape will change as well, as well as diagnosis and screening. Dr Sartor: Right, and it’s going to be touched briefly on the therapeutic landscape because if we do identify, say a BRCA1 or BRCA2 [mutation], there are a couple of opportunities for more effective treatment. One of them is olaparib, which is the PARP inhibitor that I mentioned. Also, in our personal experience, the utili- sation of a platinum-type agent can have dramatic and positive effects, even though ordinarily, in prostate cancer, that’s not the case. If people have a BRCA1 and BRCA2 muta- tion underlying the cancer and we bring in a platinum, they can have great responses. References 1. Mateo J, Carreira S, Sandhu S, et al. DNA-repair defects and olaparib in metastatic prostate cancer. N Engl J Med 2015;373:1697-1708.

cancer) we’re testing, and we’re finding a very high percentage of individuals who have defects were not previously identified. Dr Haffizulla: Knowing this associa- tion exists, can we go back to tis- sue samples that were taken years ago and look at that data to see if we could have possibly prevented or maybe altered the treatment for these particular patients? Dr Sartor: Unfortunately, retrospec- tive implications, unless we are actively treating the patient, are probably absent. I mean, if some- body is dead and gone, he is dead and gone. However, there could be [prospective] implications for the family, and that is another major issue we are encountering now. We are finding these alterations, and so now we have to counsel the family members; we have a genetic coun- sellor who is set up to be able to do that. Of course, as a medical oncologist, I don’t really have genetic coun- selling expertise. We defer that to others, but that is important for our patients and their families as well.

There is an appreciation that probably about 10% of men with advanced prostate cancer have DNA-repair gene defects, and BRCA2 is the most common. BRCA1 and BRCA2 are the majority, but also there are some ATM and other genes as well.

There are therapeutic implications in addition to implications for the family. It turns out that if someone has a DNA-repair defect, there are certain drugs we can use. There was a recent New England Journal of Medicine article on olaparib, the so-called PARP inhibitor, that was synthetically lethal when interact- ing with a mutation in some of the DNA-repair defect genes. 1 It is an amazing story because, first of all, we didn’t know that BRCA1 and BRCA2 had the link to prostate can- cer. Second, we did not understand it might have therapeutic implica- tions. So, this is new. About 10% of the men with advanced prostate cancer have DNA-repair defect genes. That is big.

Dr Oliver A Sartor, Laborde Professor, Cancer Research, Medicine and Urology Departments, Tulane School of Medicine, New Orleans, Louisiana. Dr Sartor is the editor-in-chief of the peer-reviewed, bimonthly journal Clinical Genitourinary Cancer. He is a member of several professional societies, including the American Society of Clinical Oncology, the American Association for Cancer Research, the American Urological Association, and the Society of Urologic Oncology, and board certified in internal medicine and medical oncology.

Watch the video interview with Dr Oliver Sartor on www.PracticeUpdate.com

VOL. 1 • No. 3 • 2016