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Genetic Risk Assessment for Breast Cancer

Insights From:Adam M. Brufsky, MD, University of Pittsburgh Cancer Institute; Claudine J. Isaacs, MD, Lombardi Comprehensive Cancer Center; Harold J. Burstein, MD, PhD, Harvard Medical School
Published: Tuesday, May 31, 2016


Transcript:

Harold J. Burstein, MD, PhD:
Many women have a family history of breast cancer and for a long time there has been interest in really understanding the genetic details of that family history. It’s obviously very important, both for helping a patient understand why she might have gotten breast cancer, and also for helping her understand what her risk of developing breast cancer might be if there’s a family history. So, if your mom had breast cancer, you want to know, do I have a much greater risk of developing breast cancer? And the interesting thing is that while many people have a family history, most women do not have hereditary breast cancer. Out of 100 cases of breast cancer that we see in the clinic, probably no more than 5—at the most, 10, depending on where you practice and the specific community you live in…Only a small minority of those women truly have hereditary breast cancer with a genetic predisposition. This is something that a lot of people worry about and are understandably concerned about, but it only accounts for a small minority of cases of actual breast cancer.

Beginning in the 1970s and 80s, there were elaborate genetic studies to try and look for chromosomal linkages that began to account for breast cancer in families. Mary Claire King, at University of Washington was really the pioneer in this field and deserves tremendous credit for moving it forward. Her work and the work of her colleagues around the country—and really around the world—led to the identification of two of the most important genes, the BRCA1 and the BRCA2 genes. These genes were easier to identify because they were clearly very powerful at increasing the risk of developing breast cancer. One of the interesting things about the genetic testing, as we move into the next wave, is that we are finding more and more genes, but many of them have what we call a lower penetrance, by which we mean that even if you have the gene, you’re not quite so likely to get breast cancer. This is not true for BRCA1 and 2 where you have somewhere between a 60% and 80% lifetime chance of developing breast cancer, so highly penetrant genes.

That work led to the identification of these genes and eventually led to the commercialization of testing, which has been extraordinarily helpful for patients in thinking about several things. The first is that in a women who has breast cancer, she wants to understand why she got it, and it’s very powerful to be able to do the genetic testing and to say there is a hereditary mutation—this accounts for it. Or conversely, there is not. The second thing is for family members of affected women because they want to know what their risk is if a sister, if a daughter, if a mother has developed breast cancer. And for them, this is very powerful information. It’s not always easy information. Sometimes they find out things they weren’t planning on dealing with in life, and many of us have had families where some of the siblings have the mutation and some of them don’t, and it feels like a very unfair genetic lottery. So, that raises issues, but at least you have the information.

For many women who have a family history, but not quite such an elaborate family history, they have a maternal aunt who had breast cancer or a paternal cousin, this information again can often be reassuring to help people really understand why this is happening to them and what their risks moving forward might be. One of the questions women ask us all the time when they’re diagnosed with breast cancer is I can deal with this, but I don’t want to have my kids deal with this. And so another role of the genetic testing is to reassure that patient that the breast cancer isn’t going to be something that her family is going to have to deal with generation after generation. There was a very interesting piece in the New York Times, this past week, by Gina Kolata, where she was talking about genetic testing, and she pointed out some of the pitfalls of genetic testing. And I know you’ll get into this in the program today, but the interesting thing is that while there are pitfalls, for the vast majority of women, the information is really reassuring. Remember that before you had genetic testing, you had 100% of the time uncertainty about whether this was a truly hereditary breast cancer or not. And now 95% of the time we can give women very good reassurance that they either do have, in 5% of the cases, a hereditary predisposition, or in 90% of the cases, they really don’t. And that information has a lot of clinical implications and really affects the way people feel about the disease.

Adam M. Brufsky, MD, PhD: The goals for genetic testing for risk assessment in breast cancer—and even other cancers, but we’ll focus on breast here—are really to inform a patient, in this case a woman with breast cancer or even a man with potential breast cancer, what their risk of new cancer will be. If a woman presents with breast cancer and actually fits the criteria potentially for genetic testing—and there are many criteria that we use, some are in evolution—it can guide kind of what surgical procedure she has. Because potentially if she is positive for one of these somatic mutations or germline mutations, she may have a high risk of breast and/or other cancers. And therefore, she may elect to have more extensive surgery. She may elect to have an oophorectomy, or she may elect to have certain screening procedures. It’s for women with breast cancer to guide what kind of surveillance and what kind of actual surgical procedures they’ll get. In addition, it’s also for people at risk for cancer who don’t have cancer at all. And that’s really to help them with screening and/or prophylactic surgical procedures. I think that the precision that we’ve gained in the last probably decade or two really has changed the way we manage patients.

Claudine Isaacs, MD: So, the question is, who should be tested? And that’s straightforward in some cases. In other cases, it’s somewhat more complex. Obviously, if somebody is a close family member of somebody who is known to carry a deleterious mutation, they should be referred for genetic risk evaluation and for testing. And then if we’re just looking at individuals who do not belong to hereditary breast cancer families, if you have a woman who’s diagnosed with breast cancer under the age of 50, or a triple-negative breast cancer under the age of 60—even in the absence of any family history—that’s an indication for referral for risk evaluation, or any male breast cancer patient. If somebody is of Jewish decent and they have ovarian cancer, or pancreatic cancer, or breast cancer, that’s an appropriate candidate. And then you’re really looking at more complex constellations of family history where if you have cases of younger age of onset of breast cancer, or multiple family members, or families where there’s both breast and ovarian cancer, all of those things come in together. The good news is that there are some guidelines out there that are pretty easy to look up and to follow if you’re not sure. So, NCCN has some easy and well accessible guidelines that can help people understand who should be referred for risk evaluation and testing.

Transcript Edited for Clarity
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Transcript:

Harold J. Burstein, MD, PhD:
Many women have a family history of breast cancer and for a long time there has been interest in really understanding the genetic details of that family history. It’s obviously very important, both for helping a patient understand why she might have gotten breast cancer, and also for helping her understand what her risk of developing breast cancer might be if there’s a family history. So, if your mom had breast cancer, you want to know, do I have a much greater risk of developing breast cancer? And the interesting thing is that while many people have a family history, most women do not have hereditary breast cancer. Out of 100 cases of breast cancer that we see in the clinic, probably no more than 5—at the most, 10, depending on where you practice and the specific community you live in…Only a small minority of those women truly have hereditary breast cancer with a genetic predisposition. This is something that a lot of people worry about and are understandably concerned about, but it only accounts for a small minority of cases of actual breast cancer.

Beginning in the 1970s and 80s, there were elaborate genetic studies to try and look for chromosomal linkages that began to account for breast cancer in families. Mary Claire King, at University of Washington was really the pioneer in this field and deserves tremendous credit for moving it forward. Her work and the work of her colleagues around the country—and really around the world—led to the identification of two of the most important genes, the BRCA1 and the BRCA2 genes. These genes were easier to identify because they were clearly very powerful at increasing the risk of developing breast cancer. One of the interesting things about the genetic testing, as we move into the next wave, is that we are finding more and more genes, but many of them have what we call a lower penetrance, by which we mean that even if you have the gene, you’re not quite so likely to get breast cancer. This is not true for BRCA1 and 2 where you have somewhere between a 60% and 80% lifetime chance of developing breast cancer, so highly penetrant genes.

That work led to the identification of these genes and eventually led to the commercialization of testing, which has been extraordinarily helpful for patients in thinking about several things. The first is that in a women who has breast cancer, she wants to understand why she got it, and it’s very powerful to be able to do the genetic testing and to say there is a hereditary mutation—this accounts for it. Or conversely, there is not. The second thing is for family members of affected women because they want to know what their risk is if a sister, if a daughter, if a mother has developed breast cancer. And for them, this is very powerful information. It’s not always easy information. Sometimes they find out things they weren’t planning on dealing with in life, and many of us have had families where some of the siblings have the mutation and some of them don’t, and it feels like a very unfair genetic lottery. So, that raises issues, but at least you have the information.

For many women who have a family history, but not quite such an elaborate family history, they have a maternal aunt who had breast cancer or a paternal cousin, this information again can often be reassuring to help people really understand why this is happening to them and what their risks moving forward might be. One of the questions women ask us all the time when they’re diagnosed with breast cancer is I can deal with this, but I don’t want to have my kids deal with this. And so another role of the genetic testing is to reassure that patient that the breast cancer isn’t going to be something that her family is going to have to deal with generation after generation. There was a very interesting piece in the New York Times, this past week, by Gina Kolata, where she was talking about genetic testing, and she pointed out some of the pitfalls of genetic testing. And I know you’ll get into this in the program today, but the interesting thing is that while there are pitfalls, for the vast majority of women, the information is really reassuring. Remember that before you had genetic testing, you had 100% of the time uncertainty about whether this was a truly hereditary breast cancer or not. And now 95% of the time we can give women very good reassurance that they either do have, in 5% of the cases, a hereditary predisposition, or in 90% of the cases, they really don’t. And that information has a lot of clinical implications and really affects the way people feel about the disease.

Adam M. Brufsky, MD, PhD: The goals for genetic testing for risk assessment in breast cancer—and even other cancers, but we’ll focus on breast here—are really to inform a patient, in this case a woman with breast cancer or even a man with potential breast cancer, what their risk of new cancer will be. If a woman presents with breast cancer and actually fits the criteria potentially for genetic testing—and there are many criteria that we use, some are in evolution—it can guide kind of what surgical procedure she has. Because potentially if she is positive for one of these somatic mutations or germline mutations, she may have a high risk of breast and/or other cancers. And therefore, she may elect to have more extensive surgery. She may elect to have an oophorectomy, or she may elect to have certain screening procedures. It’s for women with breast cancer to guide what kind of surveillance and what kind of actual surgical procedures they’ll get. In addition, it’s also for people at risk for cancer who don’t have cancer at all. And that’s really to help them with screening and/or prophylactic surgical procedures. I think that the precision that we’ve gained in the last probably decade or two really has changed the way we manage patients.

Claudine Isaacs, MD: So, the question is, who should be tested? And that’s straightforward in some cases. In other cases, it’s somewhat more complex. Obviously, if somebody is a close family member of somebody who is known to carry a deleterious mutation, they should be referred for genetic risk evaluation and for testing. And then if we’re just looking at individuals who do not belong to hereditary breast cancer families, if you have a woman who’s diagnosed with breast cancer under the age of 50, or a triple-negative breast cancer under the age of 60—even in the absence of any family history—that’s an indication for referral for risk evaluation, or any male breast cancer patient. If somebody is of Jewish decent and they have ovarian cancer, or pancreatic cancer, or breast cancer, that’s an appropriate candidate. And then you’re really looking at more complex constellations of family history where if you have cases of younger age of onset of breast cancer, or multiple family members, or families where there’s both breast and ovarian cancer, all of those things come in together. The good news is that there are some guidelines out there that are pretty easy to look up and to follow if you’re not sure. So, NCCN has some easy and well accessible guidelines that can help people understand who should be referred for risk evaluation and testing.

Transcript Edited for Clarity
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