Cancer early detection – genetic testing 

MD Anderson Cancer Center
Date: 03-17-2014



Dr. Michael Fish:  Welcome to Cancer Newsline, a podcast series from the University of Texas MD Anderson Cancer Center. Cancer Newsline helps you stay current with the news on cancer research, diagnosis, treatment and prevention, providing the latest information on reducing your family's cancer risk. I'm your host, Dr. Michael Fish, from the Department of General Oncology at MD Anderson Cancer Center. Today, we have a trio of star faculty that I'm pleased to be here with, which include all faculty from Clinical Cancer Genetics at MD Anderson, starting with Dr. Karen Lu, Professor and Chair of Gynecological Oncology and Reproductive Medicine, Dr. Banu Arun, Professor of Breast Medical Oncology, and Dr. Nancy You, Assistant Professor of Surgical Oncology. Welcome.

All Together: Thank you.

Dr. Michael Fish:   So, I wanted to first start out with Angelina Jolie, and I want to tell you that when I was in training, I heard Magic Johnson come out and talk about HIV. And I remember being in a patient's room and being sort of mesmerized by that whole experience. And what happened with Angelina Jolie reminds me of this -- a very important figure starts talking about a very common health problem. So, this story, I guess, is that she had bilateral mastectomy and she's 37 years old and this was all driven by a BRCA mutation. So, Dr. Arun, what is this all about, this BRCA mutation, and why does it matter to people who watch TV?

Dr. Banu Arun:  Well, the BRC gene helps to synthesize some proteins in the body that help finding problems in cells and repairs it. So, everybody has a BRC gene, but in some individuals, that gene doesn't function well. So therefore, problems in cells cannot be repaired and if these are cells who want to go into cancer cells, then they have a free pass and there is no control and checks and cancer can happen. Now, this specific BRCA gene, and there are two of those: BRCA1 and 2. Problems in these genes can cause, in the majority, two types of cancers: breast cancer and ovarian cancer. And the story with Angelina Jolie is that she has a very significant history, a family history, of cancer. Her mother had ovarian cancer. And, at one point, I think, she decided to get tested for a problem with this gene, a mutation in this gene, and was found to be positive and because of the breast and ovarian cancer risk associated with the gene mutation, she made a personal choice of doing something about it.

Dr. Michael Fish:   Well, that makes sense. So, Dr. You, are women who hear this story and hear how Angelina Jolie protected herself by making a certain choice, are they supposed to ask their doctor to get BRCA tested or is there some other way that we select who to test and who not to test?

Dr. Nancy You:  I think genetic testing is a very personal thing and it needs to be a decision that an individual patient arrives at with their physicians. There are clinical -- there are tip-offs in a person's history and a person's family history that make us suspect more for a BRCA, a problem with genes like BRCA, and the physicians may encourage them to get tested. And then, you know, I think, kind of, how do you interpret the results and what do you do given what results you're going to find is a conversation that typically should be had before the testing happens.

Dr. Michael Fish:   So it's not like mammography, where women should go out and all get tested with BRCA or they should get a mammogram and a BRCA test or how does it go?

Dr. Nancy You:  Typically, it's a more select cohort of patients who we think are at a little bit higher risk that we would recommend testing. I know you guys are changing -- like, that's like changing right now.

Dr. Banu Arun:  Keep in mind that less than 10% of, and I'm talking about breast cancers, and I think Dr. Lu talk about ovarian cancers, but it's similar, that less than 10% of breast cancers are hereditary. So, not everybody who hears the story should immediately think of oh, I need to go and get tested for BRCA because I have one family member with breast cancer. For example, a young woman who's grandmother had breast cancer at age 81. That's not the ideal scenario to undergo the testing. There are certain, what we call red flags in the family that would alert the individual or healthcare providers to consider genetic counseling and testing and that is multiple females with early onset breast cancer, families with ovarian cancer, breast cancer in men, maybe pancreas cancer. So there are certain features that we look at and then decide whether that test is appropriate for an individual. So it's not like a screening mammogram where, oh, I worry and I want this test done.

Dr. Michael Fish:   I see.

Dr. Banu Arun:  Yeah.

Dr. Michael Fish:   I see. Now, there is a story on NBC News and in the news outlets about two weeks ago arising from a paper in the Journal of Clinical Oncology and the paper talked about the fact that there was an 80% reduction in the risk of ovarian cancer and other cancers and a 77% all-cause mortality reduction. So, people were doing better if they had both of their ovaries removed. So, Dr. Lu, are women supposed to have both their breasts and both their ovaries removed?

Dr. Karen Lu:  So, what's difficult is once an individual, once a woman finds out that they have a mutation in BRCA1 or BRCA2, the next question is, what do I do to reduce my risk? So the risks are high. So if you think about ovarian cancer in a general population, the risk is about one and a half percent in a woman's lifetime to develop ovarian cancer. If you have a BRCA mutation, that increases up to 40%, even as high as 50%. So, we're talking about very different risks. Most women in the general population don't need to be doing anything in terms of screening or prevention. But if you have a lifetime risk of up to 40% or 50%, you are going to think about doing things that can effectively decrease that risk. And what that study showed is that one of the cornerstones of management is surgical prevention and that we know that by removing the ovaries and the fallopian tubes, we can essentially prevent ovarian cancer. Now this is complicated and I think Angelina Jolie is a perfect example of that. Many of the women that we will see already have cancer. That's why they had the genetic testing. And so, because they've had cancer, because they've gone through chemotherapy and often times because they're already menopausal, the decision to remove their ovaries is fairly straight forward. They don't have ovarian function anymore. There is a whole generation of women like Angelina Jolie that we call previvors; they've never had cancer before. And so they're having to face very difficult decisions because it's not like they have a cancer diagnosis and then are making a decision for treatment. These women have never had cancer and so they are having to make decisions about removing healthy organs. That will significantly change their quality of life. So, it's important to have that information. It's helpful information. But it's not as straightforward as the minute you turn 35 you should have your ovaries out. There's other things that need to be considered. We've got new strategies and so it really, I think, has to be -- I think that for these, oftentimes young women, they really need to be talking through with their physicians what all the options are and what all the implications are for these decisions.

Dr. Michael Fish:   You know, it sounds pretty complex and I'm imagining a woman whose older sister gets diagnosed with breast cancer and then goes through certain tests and is found to have a BRCA mutation, and then this woman, the younger sister who then becomes a previvor, and somebody says you might want to get tested. And then the younger woman gets tested and has the mutation as, again, in Angelina Jolie's shoes, and then if she decides to go through this surgical prevention and has both breasts removed and both ovaries removed, what does that do to her health over 20 years? How does a woman deal with the health effects of having instant menopause as a young woman?

Dr. Karen Lu:  We really are just learning as these, kind of, groups of women go through these things. We're learning about what the implications are, not just to their health, but to their, kind of, mental well-being as well. It's important to study those things. It's equally as important to study how removing the ovaries impacts all-cause mortality. It's equally important to study how it affects their quality of life. And, you know, clearly, when you remove a woman's ovaries and put them into premature menopause, they have increased risk of osteoporosis, potentially heart disease, and so we don't really know. In many of these women, we do talk to them about hormone replacement and it's a complicated discussion there as well because hormone replacement ... we don't want the benefit ... there's actually, in addition to the benefit of decreasing ovarian cancer risk when you remove the ovaries in the premenopausal period, it decreases breast cancer risk in half. So, there's a big benefit to that and so we don't know if you give hormone replacement, you know, do you lose that breast cancer risk? You probably don't. But, there are many different factors that you have to consider: their long term health, their breast cancer risk, all of these other things.

Dr. Banu Arun:  Because of the ovariectomy benefit to reduce breast cancer risk, sometimes patients choose to do the ovariectomy first and then delay the decision to do bilateral mastectomies or never do it with some type of reassurance that doing ovariectomy would reduce breast cancer risk by half, but then when they take the hormone replacement therapy, of course, how much that offsets that benefit, we don't know. And those women continue with screening. We call it more intensive surveillance with mammograms and breast MRIs. But, it is very complex and there are many different scenarios. I think ideally, a woman should not go through this by herself. I think discussing it in detail with their healthcare provider is in a constant fashion is, I think, important.

Dr. Michael Fish:    So how does the genetic counselor come into play? So a woman faces some choice like this and then the doctor says I'm going to send you to genetic counseling. So, take me through, Dr. You, what happens when the woman shows up? What is she going to go through?

Dr. Nancy You:   Yeah, so, I think in my mind, the two main jobs of genetic counseling -- well, actually, there's a few. So, a few of the things that genetic counselors do is they assess the risk of the patient. So they take a very detailed personal history. They study the pedigree of the family and the family history. So that gives us a better picture of what the risks are. And then they discuss the testing, the limitations of testing, the possible outcomes of testing, how they interpret the test results with the patient. And then, I think the third thing that they do is a lot of education. So, what, you know, what are the recommendations for surveillance, as we all ready mentioned, and what are the potential things that can be done. And I feel fairly strongly that people should not undergo genetic testing without a thorough counseling session with a genetic counselor.

Dr. Michael Fish:    Well, I'm imagining that some people probably find it frightening to be referred. They will think, I'm going to be asked things about my family that I don't actually know the answer to, people are going to put a lot of facts and figures and mutations in my head and I'll be overwhelmed, and I'll be more scared when I'm done than before I came. And so, Dr. Lu, what would you say to a woman who's worried about that before she even decides to take the referral.

Dr. Karen Lu:  You know, genetic counselors are a group of professionals who have training both in genetics, but also in counseling and they really have the ability to communicate and educate the patient, and also to comfort the patient in terms of the anxiety that surrounds having an inherited risk of cancer from their family members. So, I think we all feel very strongly that the genetic counselors play a key role in educating patients about both the benefits and some of the uncertainties around the genetic testing process.

Dr. Banu Arun:  One thing I want to add is that a referral for genetic counseling doesn't mean that that person has to do the genetic testing. It's really information gathering and understanding whether genetic testing is indicated and, after the counseling session, if the counselors indicate that it would be helpful to do the testing, it's still a personal choice. So going through the counseling is really educational, understanding the facts. It does not mean that that person has to, at the end, undergo the genetic testing.

Dr. Michael Fish:    Well, that, I think, is comforting to hear, that people still retain their choice and people are being respected for what their choices are and, really, Dr. Lu, you emphasized that it's a therapeutic session. It's not just a big educational dais. I think that's pretty useful information. Now, it sounds like genetic testing is all about breast cancer, but we send patients who have colorectal cancer and thyroid cancer and other cancers there. So, can you talk a little more about the full spectrum of what happens? Dr. You, what about, for example, these colorectal patients? Do they all get referred for genetic counseling too?

Dr. Nancy You:   Yes, so, genetic counseling and testing play a large role in GI cancers also and colorectal cancer being the third most common and third most lethal cancer in the States. We do see a lot of patients with colorectal cancer. In particular, we know that the incidence of colorectal cancer is rising among people who are younger than 50 in the States. And, when we see somebody young, less than age 50, this becomes one of the red flags that we were talking about and we think that this person may have underlying genetic disease that we should look for. And so, at MD Anderson, we actually test all patients with colorectal cancer, younger than age 50, for potential underlying genetic syndromes, which is something we do fairly uniquely, but also certainly other patients who are a little bit older but with suspicious family history or personal history. We test them also.

Dr. Michael Fish:    So, is the value of getting this genetic counseling that it would affect your own treatment for colon cancer? Or does it just affect your family's treatment, and does it make some decision about what will be taken out of your body or not taken out?

Dr. Nancy You:   Yes. That's actually a great question. And the answer applies to many of the other syndromes and other organ sites. And so, I kind of think of knowledge as being powerful in the sense that it will affect the care for the patient, him or herself. In terms of colon cancer, it can affect how much colon gets taken out. So, in somebody -- you know, kind of similar to the case of breast cancer, in somebody who has a significantly elevated risk for colorectal cancer, we may think about taking out a little bit more colon so that we decrease the amount of colon that remains at risk inside the body. In addition to the person theirself, if we can identify the gene that is mutated in the family, then all the blood relatives can get tested and so we can find out whether the relatives are at risk and actually do something active about it, whether it's surveillance or counseling or additional things we can do.

Dr. Michael Fish:    I can imagine that patients will keep thinking that when you go for testing, there's just different levels of bad news that we can find. Is there some kind of good news that comes out of this testing sometimes?

Dr. Karen Lu:  So, yes, there is. And I think you can look at it -- I think there's two ways to look at it. One, oftentimes these families have so much cancer that all of the individuals in the family are concerned about cancer. And so one of the most powerful things about genetic testing is when we can tell a young person that they are a true negative, that they don't have that substantially increased risk of cancer that accounted for, you know, their dad or their mom's cancer. So that true negative test result can be very powerful. I think the other thing is that we feel strongly that even when someone is told that they have a positive result, again, in a family where there is a lot of cancer, we have very effective preventive and early detection strategies. So again, I think it's very similar to what Nancy was saying, knowledge is power, and you're kind of shedding light and letting individuals know that there are options for them so that they potentially can avoid, you know, the cancers that their family members had.

Dr. Michael Fish:    That makes sense. So it's a way of reducing suffering due to disease and suffering due to worry and misinformation, I will say.

Dr. Banu Arun:   What we are also recently seeing is that the testing results can impact management of breast cancer patients and also ovarian cancer patients. For the first time, we now have what we call targeted agents or smart drugs, such as the PARP inhibitors, that have been shown to be effective in BRCA, for example, of related breast cancers and ovarian cancers. For BRCA related breast cancers, we also now know that adding a certain group of chemotherapeutic agents might be also beneficial. So, besides family, it might also impact not only screening and prevention, but also management -- treatment management options for the person with cancer.

Dr. Michael Fish:    So, yes, the medical oncologists are getting key information that guides therapy. So I think that's important point to make. So, Dr. Arun, if people want to know more about this in general, what are good places to get information that's accurate and understandable?

Dr. Banu Arun:   I think there are several websites that can provide information. Obviously, our clinical cancer genetics website has links to several other organizations, the American Cancer Society, the ASCO has educational website for genetics information. There are patient-driven organizations, such as FORCE. They are very active in this field. They have a great website and community and also have links to even other websites. So, it's a very big community where everybody, patients, healthcare providers, genetic counselors, work together hand-in-hand in this.

Dr. Michael Fish:    So another example of multi-disciplinary care.

Dr. Banu Arun:   Exactly.

Dr. Michael Fish:   Well, thanks to each of you for being with us today. If you have questions about anything you've heard today on Cancer Newsline, contact Ask MD Anderson at 1-877-MDA-6789 or online at Thank you for listening to this episode of Cancer Newsline. Tune in for the next podcast in our series.