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Implications for Germline BRCA Testing in Breast Cancer

Panelists:Joyce OShaugnessy, MD, Baylor University Medical Center; Tiffany A. Traina, MD, Memorial Sloan Kettering Cancer Center; Nadine M. Tung, MD, Harvard Medical School
Published: Tuesday, Apr 24, 2018



Transcript: 

Joyce O’Shaughnessy, MD: Welcome to this OncLive News Network® presentation, broadcasting live from MJH Studios. Today’s discussion will be focused on systemic therapy for hereditary breast cancer and evolving treatment strategies in this setting.

I’m your host, Dr. Joyce O’Shaughnessy. I’m the Celebrating Women’s Chair of breast cancer research at the Baylor University Medical Center, Texas Oncology and US Oncology, in Dallas, Texas. Today I’m joined by 2 colleagues who are experts in breast cancer treatment and research.

Dr. Tiffany Traina is the clinical director of the Breast Medicine Service, associate attending professor, and section head of the Triple-Negative Breast Cancer Research Program at Memorial Sloan Kettering Cancer Center; and associate professor of medicine at the Weill Cornell Medicine College of Medicine, in New York, New York.

Dr. Nadine Tung is an associate professor in the Department of Medicine at Harvard Medical School and is the director of both the Breast Medical Oncology Service and the Cancer Risk and Prevention Program at Beth Israel Deaconess Medical Center, in Boston, Massachusetts.

With that, we’re going to start by talking about BRCA testing. We’ve been working hard, over the years, to remember to try to do germline testing in women who are newly diagnosed with breast cancer. But there really hasn’t been so much of an emphasis in the metastatic setting. And now here we are, because of the availability of olaparib, and other PARP inhibitors (soon to come), in the metastatic setting. So who is supposed to be tested, in the metastatic setting, for germline BRCA? Nadine?

Nadine Tung, MD: There are new criteria, put out by NCCN [National Comprehensive Cancer Network], that state that if a woman has metastatic HER2-negative breast cancer and is appropriate for treatment with olaparib, specifically (because that’s now approved by the FDA), germline BRCA testing is appropriate for that patient. It’s not entirely clear how many additional BRCA mutations we’re going to find, compared with the previous NCCN criteria, because that was extremely sensitive for finding BRCA carriers in newly diagnosed patients in the early setting.

But nevertheless, it does allow us to be more permissive in our genetic testing. I don’t know that a triple-negative breast cancer patient has to be limited to a diagnosis at age 60 or younger, for example. One of the questions that really comes up is, Do we test women in the initial setting? Do we test them in the metastatic setting? Do we do germline testing? Do we do somatic testing? There are a few take-home messages that are probably good to remember. In the early setting, when a patient is appropriate for germline BRCA testing, they should be tested. It has implications for their surgery, etcetera.

But in the metastatic setting, it can get a little tricky. We’re doing a lot of somatic testing to guide our treatment. If a somatic BRCA mutation is identified, those patients should be reflexed to germline testing. Most patients, but not all, will have a germline BRCA mutation. About 4% will just have a somatic mutation in breast cancer. So positive reflexes to germline—I would say that no matter what the somatic tumor testing shows, if that patient meets traditional NCCN criteria for germline testing, do the germline BRCA testing. Sometimes the tumor won’t show it, but the patient has the germline mutation. You don’t want to miss it.

And then, the last thing I would say is to consider the VUS [variant of unknown significance]. We’ve really educated our clinicians on the point that a variant of unknown significance should not be treated like a BRCA mutation. In the germline setting, we don’t act on VUS. In the somatic testing, I think it’s still evolving. If I were to get a BRCA1 or BRCA2 VUS in my somatic testing, I would check the databases (like ClinVar) for germline testing. If I could prove it was a benign change, or a VUS, I would ignore it. Otherwise, I would reflex to germline testing because I don’t think the somatic databases are as established or as well worked out.

Joyce O’Shaughnessy, MD: Thank you. That is terrific, and it’s terrific that the NCCN now has said that anyone with HER2-negative disease who might be a candidate for olaparib or, in the future, other PARP inhibitors is eligible for testing. That really gives us a lot of leeway to do so for these patients—if we can remember to do it in the metastatic setting, which is sometimes challenging with everything else that is going on with those patients.

Transcript Edited for Clarity 
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Transcript: 

Joyce O’Shaughnessy, MD: Welcome to this OncLive News Network® presentation, broadcasting live from MJH Studios. Today’s discussion will be focused on systemic therapy for hereditary breast cancer and evolving treatment strategies in this setting.

I’m your host, Dr. Joyce O’Shaughnessy. I’m the Celebrating Women’s Chair of breast cancer research at the Baylor University Medical Center, Texas Oncology and US Oncology, in Dallas, Texas. Today I’m joined by 2 colleagues who are experts in breast cancer treatment and research.

Dr. Tiffany Traina is the clinical director of the Breast Medicine Service, associate attending professor, and section head of the Triple-Negative Breast Cancer Research Program at Memorial Sloan Kettering Cancer Center; and associate professor of medicine at the Weill Cornell Medicine College of Medicine, in New York, New York.

Dr. Nadine Tung is an associate professor in the Department of Medicine at Harvard Medical School and is the director of both the Breast Medical Oncology Service and the Cancer Risk and Prevention Program at Beth Israel Deaconess Medical Center, in Boston, Massachusetts.

With that, we’re going to start by talking about BRCA testing. We’ve been working hard, over the years, to remember to try to do germline testing in women who are newly diagnosed with breast cancer. But there really hasn’t been so much of an emphasis in the metastatic setting. And now here we are, because of the availability of olaparib, and other PARP inhibitors (soon to come), in the metastatic setting. So who is supposed to be tested, in the metastatic setting, for germline BRCA? Nadine?

Nadine Tung, MD: There are new criteria, put out by NCCN [National Comprehensive Cancer Network], that state that if a woman has metastatic HER2-negative breast cancer and is appropriate for treatment with olaparib, specifically (because that’s now approved by the FDA), germline BRCA testing is appropriate for that patient. It’s not entirely clear how many additional BRCA mutations we’re going to find, compared with the previous NCCN criteria, because that was extremely sensitive for finding BRCA carriers in newly diagnosed patients in the early setting.

But nevertheless, it does allow us to be more permissive in our genetic testing. I don’t know that a triple-negative breast cancer patient has to be limited to a diagnosis at age 60 or younger, for example. One of the questions that really comes up is, Do we test women in the initial setting? Do we test them in the metastatic setting? Do we do germline testing? Do we do somatic testing? There are a few take-home messages that are probably good to remember. In the early setting, when a patient is appropriate for germline BRCA testing, they should be tested. It has implications for their surgery, etcetera.

But in the metastatic setting, it can get a little tricky. We’re doing a lot of somatic testing to guide our treatment. If a somatic BRCA mutation is identified, those patients should be reflexed to germline testing. Most patients, but not all, will have a germline BRCA mutation. About 4% will just have a somatic mutation in breast cancer. So positive reflexes to germline—I would say that no matter what the somatic tumor testing shows, if that patient meets traditional NCCN criteria for germline testing, do the germline BRCA testing. Sometimes the tumor won’t show it, but the patient has the germline mutation. You don’t want to miss it.

And then, the last thing I would say is to consider the VUS [variant of unknown significance]. We’ve really educated our clinicians on the point that a variant of unknown significance should not be treated like a BRCA mutation. In the germline setting, we don’t act on VUS. In the somatic testing, I think it’s still evolving. If I were to get a BRCA1 or BRCA2 VUS in my somatic testing, I would check the databases (like ClinVar) for germline testing. If I could prove it was a benign change, or a VUS, I would ignore it. Otherwise, I would reflex to germline testing because I don’t think the somatic databases are as established or as well worked out.

Joyce O’Shaughnessy, MD: Thank you. That is terrific, and it’s terrific that the NCCN now has said that anyone with HER2-negative disease who might be a candidate for olaparib or, in the future, other PARP inhibitors is eligible for testing. That really gives us a lot of leeway to do so for these patients—if we can remember to do it in the metastatic setting, which is sometimes challenging with everything else that is going on with those patients.

Transcript Edited for Clarity 
View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Cancer Summaries and Commentaries™: Update from Chicago: Advances in the Treatment of Breast CancerJul 31, 20181.0
Community Practice Connections™: Medical Crossfire®: Translating Lessons Learned with PARP Inhibition to the Treatment of Breast Cancer—Expert Exchanges on Novel Strategies to Personalize CareAug 29, 20181.5
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