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BRCA-Mutated Triple-Negative Breast Cancer

Panelists: Adam M. Brufsky, MD, PhD, University of Pittsburgh Cancer Institute; Carlos L. Arteaga, MD, Vanderbilt University; Jose Baselga, MD, PhD, Memorial Sloan Kettering Cancer Center; Kimberly Blackwell, MD, Duke Cancer Institute; Debu Tripathy, MD, University of Texas MD Anderson Cancer Center; Denise A. Yardley, MD, Sarah Cannon Research Institute; Hope S. Rugo, MD, UCSF Helen Diller Family Comprehensive Cancer Center
Published: Monday, Jul 24, 2017



Transcript:

Adam M. Brufsky, MD, PhD:
Switching to platinums for a minute, away from the capecitabine: The issue with platinums is that we have a potential biomarker. So do people believe in using BRCA status as a biomarker for platinum sensitivity?

José Baselga, MD, PhD: Yes.

Debu Tripathy, MD: I think it’s true. The TNT trial showed that. There has hence been a bit from other trials, like the GeparSixto trial. Now, what impact it will have, what role other drugs such as PARP inhibitors will play in that landscape, is still an open question. But if you’re simply asking that question as to platinum, I think platinums are not necessarily uniquely helpful over other chemotherapy in triple-negative disease, but in BRCA mutation carriers, they are better.

Adam M. Brufsky, MD, PhD: So are you sequencing everybody who walks in the door now for BRCA status?

Kimberly L. Blackwell, MD: Do you mean germ line?

Adam M. Brufsky, MD, PhD: A person with triple-negative breast cancer walks in the door. Do you test BRCA status in the absence of family history?

Kimberly L. Blackwell, MD: Yes. In the early-stage setting, if they are eligible for platinum-based therapy, if I’m going to give it in the preoperative setting—I don’t give platinums in the adjuvant setting, but if they have a big enough tumor that I’m considering preoperative therapy—I will send them for testing. And I think after this ASCO meeting, for the majority, if not all, of my patients facing recurrent or metastatic triple-negative breast cancer, the standard will become that they need to have BRCA testing.

Adam M. Brufsky, MD, PhD: Go ahead, Carlos.

Carlos L. Arteaga, MD: Based on the data of Fergus Couch, triple-negative patients with sporadic-looking cancer who have a family history have up to a 20% chance of having a germ line mutation.

Adam M. Brufsky, MD, PhD: But what about the ones who don’t have a family history? So if someone walks in the door—say she has a mom and 2 sisters who don’t have breast cancer, but she has a triple-negative breast cancer, and she’s 50.

Carlos L. Arteaga, MD: I would rely on the advice of genetic counselors and the need or not of that patient having germ line testing.

Debu Tripathy, MD: But just to be clear, the NCCN guidelines and the American Society of Human Genetics are recommending…

Adam M. Brufsky, MD, PhD: Everybody under 60 years with triple-negative, I agree. The real question, especially if we’re going to talk about PARP inhibitors in a second, but at least with platinum—we’ve turned this now from a screening decision to a therapeutic decision. It’s a totally different thing. So we’re still worried about screening the family for mutations, but it now really will determine our therapy.

Debu Tripathy, MD: Right.

José Baselga, MD, PhD: Yes.

Kimberly L. Blackwell, MD: Yes. And again, we have a 1-out-of-5 chance of detecting HER2 amplification, 1 out of 3, and we have a therapy linked to that, and we test for it uniformly. I think BRCA is at that point in the metastatic setting.

Adam M. Brufsky, MD, PhD: The difference between BRCA and HER2 is that there are implications for people other than the patients.

Kimberly L. Blackwell, MD: And we as a society will have to deal with that.

Adam M. Brufsky, MD, PhD: How are we going to do that?

Kimberly L. Blackwell, MD: Precision medicine is here. You can have your own DNA sequenced, and it has implications for your own family members too. So I don’t think this is a unique example. We’re going to run out of time if we have a discussion about precision medicine, but honestly, I think we’re going to have to embrace it now.

José Baselga, MD, PhD: We decided to offer to our patients, now that we sequence a lot of tumors every year, the germ line data—now they can sign a consent form. We encourage them to obtain a consent form. Our uptake has been incredibly high. Patients want to know if you offer it to them. Interestingly enough, the people who were more reserved were actually the experts.

Adam M. Brufsky, MD, PhD: Really?

José Baselga, MD, PhD: Yes. The physicians are the ones who said, “My God, this is going to be so complex. Nobody will sign up.” We opened up the trial, we opened up the consent, and the take-up has been incredibly high. So we will need to learn to live with information that can determine outcome to therapy and prognosis, and we just have to live with this.

Carlos L. Arteaga, MD: Actually, in some cases at our institution, we, as at your institutions, sequence anybody with triple-negative and metastatic disease who has stage 4 disease and is eligible for a trial. So there will be a way of getting through the back door to a germ line alteration, and we seldom find one in the patient who clearly doesn’t have a family history.

Kimberly L. Blackwell, MD: I think it’s a good time to enter the field of genetic counseling. I’m encouraging both of my children, and there’s a national shortage.

Adam M. Brufsky, MD, PhD: There’s a total shortage. That’s the problem: There’s no one to counsel the patients.

Kimberly L. Blackwell, MD: And so I think every practice is going to have to deal with this in a unique way. They’re going to have to look at the vendors of the different assays. Do they have remote genetic counselors? Because that’s the reality in the rural United States: There aren’t genetic counselors, and this burden is going to fall on the treating oncologists.

Adam M. Brufsky, MD, PhD: Even on the primary care doctor. Yes, I agree.

Kimberly L. Blackwell, MD: I’m more worried about that than actually doing the testing, and the implications are helping patients and providers really figure out what these data all mean.

Transcript Edited for Clarity

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Transcript:

Adam M. Brufsky, MD, PhD:
Switching to platinums for a minute, away from the capecitabine: The issue with platinums is that we have a potential biomarker. So do people believe in using BRCA status as a biomarker for platinum sensitivity?

José Baselga, MD, PhD: Yes.

Debu Tripathy, MD: I think it’s true. The TNT trial showed that. There has hence been a bit from other trials, like the GeparSixto trial. Now, what impact it will have, what role other drugs such as PARP inhibitors will play in that landscape, is still an open question. But if you’re simply asking that question as to platinum, I think platinums are not necessarily uniquely helpful over other chemotherapy in triple-negative disease, but in BRCA mutation carriers, they are better.

Adam M. Brufsky, MD, PhD: So are you sequencing everybody who walks in the door now for BRCA status?

Kimberly L. Blackwell, MD: Do you mean germ line?

Adam M. Brufsky, MD, PhD: A person with triple-negative breast cancer walks in the door. Do you test BRCA status in the absence of family history?

Kimberly L. Blackwell, MD: Yes. In the early-stage setting, if they are eligible for platinum-based therapy, if I’m going to give it in the preoperative setting—I don’t give platinums in the adjuvant setting, but if they have a big enough tumor that I’m considering preoperative therapy—I will send them for testing. And I think after this ASCO meeting, for the majority, if not all, of my patients facing recurrent or metastatic triple-negative breast cancer, the standard will become that they need to have BRCA testing.

Adam M. Brufsky, MD, PhD: Go ahead, Carlos.

Carlos L. Arteaga, MD: Based on the data of Fergus Couch, triple-negative patients with sporadic-looking cancer who have a family history have up to a 20% chance of having a germ line mutation.

Adam M. Brufsky, MD, PhD: But what about the ones who don’t have a family history? So if someone walks in the door—say she has a mom and 2 sisters who don’t have breast cancer, but she has a triple-negative breast cancer, and she’s 50.

Carlos L. Arteaga, MD: I would rely on the advice of genetic counselors and the need or not of that patient having germ line testing.

Debu Tripathy, MD: But just to be clear, the NCCN guidelines and the American Society of Human Genetics are recommending…

Adam M. Brufsky, MD, PhD: Everybody under 60 years with triple-negative, I agree. The real question, especially if we’re going to talk about PARP inhibitors in a second, but at least with platinum—we’ve turned this now from a screening decision to a therapeutic decision. It’s a totally different thing. So we’re still worried about screening the family for mutations, but it now really will determine our therapy.

Debu Tripathy, MD: Right.

José Baselga, MD, PhD: Yes.

Kimberly L. Blackwell, MD: Yes. And again, we have a 1-out-of-5 chance of detecting HER2 amplification, 1 out of 3, and we have a therapy linked to that, and we test for it uniformly. I think BRCA is at that point in the metastatic setting.

Adam M. Brufsky, MD, PhD: The difference between BRCA and HER2 is that there are implications for people other than the patients.

Kimberly L. Blackwell, MD: And we as a society will have to deal with that.

Adam M. Brufsky, MD, PhD: How are we going to do that?

Kimberly L. Blackwell, MD: Precision medicine is here. You can have your own DNA sequenced, and it has implications for your own family members too. So I don’t think this is a unique example. We’re going to run out of time if we have a discussion about precision medicine, but honestly, I think we’re going to have to embrace it now.

José Baselga, MD, PhD: We decided to offer to our patients, now that we sequence a lot of tumors every year, the germ line data—now they can sign a consent form. We encourage them to obtain a consent form. Our uptake has been incredibly high. Patients want to know if you offer it to them. Interestingly enough, the people who were more reserved were actually the experts.

Adam M. Brufsky, MD, PhD: Really?

José Baselga, MD, PhD: Yes. The physicians are the ones who said, “My God, this is going to be so complex. Nobody will sign up.” We opened up the trial, we opened up the consent, and the take-up has been incredibly high. So we will need to learn to live with information that can determine outcome to therapy and prognosis, and we just have to live with this.

Carlos L. Arteaga, MD: Actually, in some cases at our institution, we, as at your institutions, sequence anybody with triple-negative and metastatic disease who has stage 4 disease and is eligible for a trial. So there will be a way of getting through the back door to a germ line alteration, and we seldom find one in the patient who clearly doesn’t have a family history.

Kimberly L. Blackwell, MD: I think it’s a good time to enter the field of genetic counseling. I’m encouraging both of my children, and there’s a national shortage.

Adam M. Brufsky, MD, PhD: There’s a total shortage. That’s the problem: There’s no one to counsel the patients.

Kimberly L. Blackwell, MD: And so I think every practice is going to have to deal with this in a unique way. They’re going to have to look at the vendors of the different assays. Do they have remote genetic counselors? Because that’s the reality in the rural United States: There aren’t genetic counselors, and this burden is going to fall on the treating oncologists.

Adam M. Brufsky, MD, PhD: Even on the primary care doctor. Yes, I agree.

Kimberly L. Blackwell, MD: I’m more worried about that than actually doing the testing, and the implications are helping patients and providers really figure out what these data all mean.

Transcript Edited for Clarity
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