Sep 12, 2019
Welcome to the ASCO Daily News podcast. I'm Lauren Davis, and joining me today is Dr. Larissa Korde whose research interests focus on breast cancer treatment and prevention at the National Institutes of Health. Today we're talking about breast cancer screening as it relates to bracket gene mutations. Dr. Korde, welcome to the podcast.
Thank you for having me.
We're glad you're here. Although 12% of women in the United States will develop breast cancer sometime during their lives, approximately 72% of women who inherit the BRCA1 mutation and about 69% of women who inherit the BRCA2 mutation will develop breast cancer by the age of 80. Recently the US Preventive Services Task Force expanded the recommendation of patients who should be screened for the BRCA1 and BRCA2 genetic mutation, which is associated with multiple cancer types. How did this update come about?
The US Preventive Services Task Force last presented guidelines on this topic in 2013. The recent publication in the Journal of the American Medical Association is an update, and it reviews the evidence that has come about since 2013. It's important to note that these recommendations are not actually about who should be tested for BRCA1 or 2 mutations. What the recommendations address is really who should be screened and that screening would be evaluation of family history.
So the screening with family history is designed to identify which patients should be referred for further evaluation by a provider experience in genetic counseling and testing who can then make recommendations regarding actually having a gene test. The task force recommends that primary care providers assess women with a personal or family history of breast or ovarian cancer and ovarian includes fallopian tube and peritoneal cancers. And they also recommend that those who have an ancestry associated with a BRCA1 or 2 mutation should be assessed using a family history assessment tool.
There are a number of brief assessment tools that can be used in the clinic setting and are designed to assist providers in identifying which patients should be referred for genetic counseling and then if appropriate for genetic testing. Also the task force recommends against routine assessment and referral in patients that do not meet their set criteria.
The important update is that compared to the 2013 guideline, the population for whom risk assessment is deemed appropriate is broader, and specifically it's been expanded to include those women with a personal history of breast or ovarian cancer and those with a specific ancestry. The ancestry part of this was met to increase awareness of the strong association between BRCA1 and 2 mutations in Ashkenazi Jewish ancestry. Again, though, this is not a blanket recommendation that all women of Ashkenazi Jewish ancestry should be tested for BRCA1 and 2 mutations, just that the knowledge of ancestry should consider-- that should trigger additional evaluation.
There are certainly schools of thought that a more inclusive approach is needed. For example, there are folks who advocate for universal mutation testing in all women with breast cancer or all women with Ashkenazi Jewish descent while others favor a more targeted approach. These recommendations call for the more targeted and step-wise approach.
So the first step would be evaluation of personal and family history and ancestry followed by referral of patients that meet a certain threshold of risk. And then finally followed by testing if it's appropriate after counsel.
That's great. Sounds like it's a lot more about finding out who really needs to be tested and not so much about the test itself. So how can this update improve outcomes for patients?
Well, I think the basic goal here is that if we can do a better job at identifying who to screen for the BRCA1 and 2 mutation, then we can do a better job of offering appropriate interventions to those who take the test and test positive. And that can take many forms. The most obvious here is that those who have the highest likelihood of having the BRCA mutation will be referred for the appropriate counseling, and then they can make the decision with the advice of their providers about whether or not to undergo testing.
And, of course, there are also downstream effects. Once a patient is identified as having a BRCA mutation, she can be offered preventive interventions such as prophylactic mastectomy or [INAUDIBLE], and she can be offered more intensive cancer screening. It's important to note here that the recommendations were expanded to include women with a personal history of cancer because we know that these women are at risk for developing a second cancer. And that's important information, particularly for a patient whose original cancer was treated with curative intent.
Something that was outside of the scope of this guideline but which I think is becoming increasingly important in the oncology community is that [INAUDIBLE] genetic information can now be used to select therapies for patients with cancer. Specifically PARP inhibitors are FDA approved for treatment of metastatic breast cancer in women with a germline BRCA mutation and are being studied in other cancers and also in the earlier stage study. So this information clearly has treatment implications.
Lastly, the identification of patients that carry a BRCA
mutation leads to what we call cascade testing. That is once you
know someone has the mutation, you can offer mutation testing to
their family members, and those who test positive can be offered
appropriate intervention. I think that this is definitely a
That sounds very promising. Do you have any concerns about the new guidelines in terms of how they will be interpreted?
No real concerns about how the guidelines will be interpreted. I think they're pretty straightforward, and they do help to expand the population who should be eligible for testing or at least screen for referral to a genetic counselor.
So I think it's important here to note that there's a lot of issues in genetic screening and testing that the guidelines do not address, primarily because there are not enough data on which to base recommendations. These are issues that I think will become more pressing in the future and hopefully can be addressed in future guidelines.
One important issue with multi-gene panel testing. Since the guideline doesn't explicitly state what gene testing should occur, just that patients should be screened and referred, it does not get into which test should be used once someone is identified having it-- identified as having a high enough risk of carrying a mutation to be referred. Multi-gene panels are becoming increasingly prevalent, and there's a lot of variation in which genes are included in panels and even in whether a particular abnormality found is classified as a deleterious mutation, as a variant of uncertain significance, or as a benign polymorphism.
Also some panels contain genes for which they're not clear clinical implications in terms of what cancer screening or preventive interventions should be offered to patients who carry these genes. So while this is outside of the scope of the guidelines, I think it's important because the information in the guideline is geared towards primary care providers. And so when they make a referral for genetic screening and testing, they need to be aware of the downstream consequences and particularly about how to counsel and treat a patient who is found to have the mutation other than BRCA1 or 2. This is something that's going to come up in clinical practice, and so I think it's important for providers to be educated about the range of possibilities.
The other issue that I want to raise, which again is not addressed in the guidelines due to a lack of available data but which is nonetheless important for providers to be aware of, is direct to consumer testing. For example, one of the very kind of consumer panels that you see on TV all the time includes evaluation for one of the [INAUDIBLE] mutations in BRCA1 and 2 that are prevalent in the Ashkenazi Jewish population.
So you could imagine a scenario where a patient with a strong family history comes in and she's asked about her family history of breast or ovarian cancer and then just says, oh, I already have the gene test. It was negative. And what that patient may mean is that they did this direct to consumer panel, and they don't have one of the three [INAUDIBLE] mutations.
But it's not comprehensive testing. So if the family history is
indicative, this person should still be referred to a genetics
provider for counseling and testing that would include looking for
all the possible mutations in BRCA1 and 2, not just these three
[INAUDIBLE] mutations and possibly looking at other genes
associated with breast and ovarian cancer as well. So without a
working knowledge about what tests are out there, this is a patient
who could be missed or who could be counseled inappropriately.
That's a very important distinction. What should clinicians tell their patients who have questions or perceptions about over testing?
I don't think these guidelines will lead to over testing. They identify appropriate specific populations of women that should be referred for a more thorough genetic evaluation. And the end result there is a referral for more information, not necessarily a test. After meeting with the genetic counselor, the patient can make an informed decision about whether or not to pursue testing and then about what type of testing to do.
Actually I think under testing is much more of a problem-- is
much more the problem that we currently face. Susan [INAUDIBLE]
pointed out in her editorial that accompanied the Preventive
Services Task Force recommendation that although it's estimated
that about 15% of women with ovarian cancer have a BRCA mutation,
studies have shown that less than 30% of such patients were tested.
So the inclusion of women with a personal history of cancer in
these guidelines is definitely an important step forward.
Under testing is also a substantial issue in underrepresented minorities and those with a lower socioeconomic status. Access to care is an issue for those living in rural areas, and this is a problem that might be alleviated through things like telegenetics. I was listening to a talk yesterday about health disparities and how telemedicine might be helpful, and the speaker said that any provider interaction that does not require a physical exam can be done through telemedicine.
I think that's true of genetic counseling. There are also ongoing studies evaluating alternative models providing genetic education and counseling, and I think these will become increasingly important in the future and can hopefully help to address the issue of under testing.
Absolutely. What an important point. Again today my guest has been Dr. Larisa Korde. Thank you so much for being on our podcast today.
It's my pleasure and thank you for having me.
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