Expert Stresses Importance of Genetic Testing in Ovarian Cancer

Deborah Krakow, MD

The known heritable conditions that pose an additional risk of developing ovarian cancer include a mutation in the BRCA1/2 gene, Lynch syndrome, Gorlin syndrome, and multiple endocrine neoplasia type 1 (MEN1), said Deborah Krakow, MD.

In an interview at the 2018 OncLive^® State of the Science Summit™ on Ovarian Cancer, Krakow underscored the value of a patient’s family history and its implications on genetic counseling: “Family history is the most important tool that we have.”

OncLive: What did your presentation on genetic counseling focus on?

How accurate are prediction models in determining who should get genetic testing?

Is a negative result always accurate?

What is an unknown significance result indicative of?

Krakow, professor and chair, Department of Obstetrics and Gynecology, professor of orthopaedic surgery and human genetics, University of California, Los Angeles, discussed the patient populations who should undergo testing and the spectrum of possible results.Krakow: I focused on the genetic basis of ovarian cancer in a heritable form. These are patients who have breast or ovarian cancer because they inherited a mutation from one of their parents. It accounts for approximately 10% of individuals who get ovarian cancer. The major genes that are involved are BRCA1/2 and some rare [conditions], including Lynch syndrome, Gorlin syndrome, and MEN1.It is a very good question. If your family history includes a firstdegree relative who has ovarian cancer and you have either ovarian or breast cancer, you should get tested for the known high-risk genes. A patient who is Ashkenazi Jewish and is diagnosed with ovarian cancer, even without a known family history of breast or ovarian cancer, should be tested. Approximately, 1% to 2% of Ashkenazi Jewish women have the same mutation in BRCA1. What is interesting is that all populations report changes in BRCA1/2, so it is not unique to one population. However, it has been enriched in the Ashkenazi Jewish population.If you get a negative result that comes from a reputable lab, then you can rest assured that you don’t carry BRCA1/2 or whatever the gene in question is.We all don’t look the same. Some of us have red hair and some of us have blonde hair. Those [traits] are based on changes in our genome that encode for making the hair protein a different color. When we sequence a large gene like BRCA1, the sequences will not be the same in everyone. Therefore, when patients who have ovarian cancer all have the same change in the BRCA1 gene, like Ashkenazi Jewish women who are missing 2 letters, we know that has to be real. It’s not a coincidence that so many people who have ovarian cancer have the same change.

What is an area of research you would like to see addressed?

However, when we sequence peoples’ genes frequently, we find changes that haven’t been reported in other people with ovarian cancer. We don’t know whether that change is producing the disease or just happens to be a sequence change that explains why we are not all identical people. It can be very difficult to determine. Companies have been sequencing for a long time and have very large databases of mutations. A single mutation that has never been seen before may just be a benign variant that we have never seen.In the United States, the average person usually can’t tell you the last 2 generations of their family history. For many people, cancer may be in their family.

Family history is the most important tool that we have. However, I go back and forth. Everyone should have a sequence analysis done when we’re born so we know what their high-risk genes are. If you do this, do you spend your whole life waiting for the shoe to drop?

There is this constant debate among geneticists about this great tool that we have and how to best use it so that it’s actionable. Families should have open communication and try, particularly for [people with] BRCA1/2 mutations who don’t have ovarian or breast cancer, to have shared information because there are actionable things that you can do.