Dr. Ramez N. Eskander spearheads a discussion on genetic testing and familial risk as it relates to ovarian cancer.
PUBLISHED October 18, 2019
Shubham Pant, M.D.: Dr. Eskander, we talked about this a little before. Doña said she had a family history of cancer. Her dad had cancer. In women with ovarian cancer, is it common to have a family history? What kind of mutations do you see? What should they be aware of?
Ramez N. Eskander, M.D.: This is really an important topic and very timely. We’ve learned a lot about this over the last 5 to 10 years, a lot more than we had known previously. And the reality is there’s a proportion of ovarian cancer patients who do have a genetic predisposition to developing the disease. And we’re learning more and more about what these alterations are that may predispose patients to having ovarian cancer, or fallopian cancer or primary peritoneal cancer — all of them as onw family.
Based on the information we have now, we think as many as 15% to 20% of patients who have a high-grade serous ovarian cancer can harbor a genetic alteration that predisposes them to developing these cancers. And most commonly it’s the BRCA1 and BRCA2 mutations. There are other mutations that are involved in this family of genes that are necessary for DNA repair, and we’re identifying additional ones like RAD51C that also increase the risk of ovarian cancer or breast cancer. I think with time, we’re going to continue to add to this list. We have 15% to 20% right now where you have a genetic inherited predisposition, and that’s independent from the risk that may arise in alterations that we don’t know about yet. But that may add to that percentage in the future. So it’s not a meaningless number or a small percentage by any means. It’s a true number of patients who have these alterations, and this has a very important impact on diagnosis, treatment in family and education, etc.
Shubham Pant, M.D.: When patients see you with ovarian cancer for the first time, do you test everybody? Let’s say Doña had a family history. I think her father had esophagus cancer. We were talking about this before. But let’s say people come and say, “Hey, I have zero family history of cancer.” Do you screen everybody, or do you screen specifically patients like Doña who come and give you a family history of cancer?
Ramez N. Eskander, M.D.: We’ve gone away from using the family history as a guide to testing, and that’s based on literature and data that we’ve learned over the past several years. We test all epithelial ovarian cancer patients. Really all ovarian cancer patients now are recommended to undergo genetic testing. And in addition to that, if the resources are available, genetic counseling to better understand it. Admittedly, physicians aren’t very good at harvesting and acquiring a good comprehensive family history, because it’s very time intensive. There may be things that we think don’t exist that truly exist. And there are data that suggest that up to half, 50%, of the women who have a BRCA alteration in cancer may have no family history that they’re aware of before they were diagnosed with their cancer and identified to have a BRCA mutation. For those reasons, we really encourage and counsel — and it’s common practice now — to test all our ovarian cancer patients for an underlying genetic predisposition.
Shubham Pant, M.D.: Dr. Eskander, which one is more common, BRCA1 or BRCA2?
Ramez N. Eskander, M.D.: BRCA1 mutations are more common than BRCA2 mutations.
Shubham Pant, M.D.: So you test them all, and let’s say somebody has a mutation, do you normally refer them to genetic counseling so that they can talk to a specialist for that? Do you offer them that yourself?
Ramez N. Eskander, M.D.: I will talk to the patient, and — if they have family members present with them during the visit — talk to them about the results, explain what the results mean. But I do always refer to genetic counselors. We’re fortunate enough to have a very good genetic counseling program. And the reason is that to invest the time that the patient and the family deserve to truly understand the implications of these genetic alterations requires, I’d say, at least an hour, an hour and 15 minutes. Really sit down with additional family members, talk about and answer the questions they may have — that the patient may not have but their sister, or their brother, or their child who accompanies them to the visit may have — is really important. And having a good genetic counselor who’s able to sit down and review the implications is a great resource.
Shubham Pant, M.D.: What reactions do you normally see of some of the family members who go, “I don’t want to know about it.” Tell me about the range that you see.
Ramez N. Eskander, M.D.: It’s a mixed bag. It’s always hard. Sometimes patients actually carry a lot of guilt when they realize that they’re a BRCA mutation carrier because they feel as if they are putting their children at risk or they didn’t know what the impact may be on their siblings. And I try to reassure them and say, no, what you’ve done is essentially maybe given your child an opportunity to be saved by never being diagnosed with a cancer and having a risk-reducing intervention.
Shubham Pant, M.D.: Exactly, yes.
Ramez N. Eskander, M.D.: But the reaction is varied. Some patients have not very much of a reaction and say, “OK, we’ll deal with it” and “I’ll have to speak to the genetic counselor.” Some carry a lot of guilt. Others honestly don’t really even understand what any of this means, and it takes a lot of time for them to truly process it and understand what genetics are and what does this mean to have an inherited alteration, and to connect the dots to how that might affect their family members, their children. It’s hard to predict, but it’s a variable reaction.
Shubham Pant, M.D.: So much information. Dr. Hirst, what do you think about that about that reaction of saying, “I’m fine right now, and I may be carrying this gene,” both from the patient side and from the family member side?
Jeremy Hirst, M.D.: I think that has changed a lot recently, especially with more commercially available direct-to-consumer testing. People are getting more familiar with what some of that means, but patients have a really wide range of backgrounds of understanding what genetics are and what do these tests eventually mean. But it can be huge. Whether it’s a younger woman whose mom is there and feels like, oh my gosh, did I give this to my daughter who’s now ill? Is that patient feeling that I’ve put my children at greater risk? There’s a lot of reassurance that we can’t control our genes, and we now have information that can help us hopefully take steps to mitigate whatever risk we now know we have.
Shubham Pant, M.D.: I think that’s very important, because it’s really important for patients to understand that it’s not their fault, frankly. It’s just that you inherited these genes, and now you have the information that you can act on. I think just like maybe with Doña, her dad somehow had this thought process saying, “Hey, remember, if you are in your 50s and everything, if you don’t feel well, go to a physician.” I think that worked out in your well-being.