PracticeUpdate: Haematology & Oncology

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.

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.

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 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

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.

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.

Genetic testing in

patients with relevant

family history in

prostate cancer

Interview with Oliver Sartor, MD

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.

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

FEATURE ARTICLE

VOL. 1 • No. 3 • 2016