Film and Panel Discussion: In The Family: With Director Joanna Rudnick And UM Cancer Research Experts

Mon, 05/16/2005 - 11:33am

When: March 17, 2009 at the Downtown Library: Multi-Purpose Room

When Chicago filmmaker Joanna Rudnick tested positive for the breast cancer gene at age 27, she knew the information could save her life. The question was what to do about it? At this event, Joanna Rudnick will introduce In the Family, the film that tells her intensely personal story. In this unblinking documentary, we learn that Joanna, whose family has a history of breast and ovarian cancer, took advantage of breakthroughs in genetic research to prepare herself for her own future. Intensely personal and timely, In The Family (which is not rated) is a groundbreaking investigation that attempts to answer the questions: How much do you sacrifice to survive? The film will be followed by a panel discussion with Joanna and a team of leading experts in medical cancer research.In addition to filmmaker Joanna Rudnick, the post-film panel will feature:- Daniel F. Hayes, M.D., Clinical Director of the Breast Oncology Program at the UM Comprehensive Cancer Center, whose research is internationally recognized in the identification of tumor markers, which help to properly evaluate patients with breast cancer- Lisa Newman, M.D., M.P.H., Director of the Breast Care Center of the UM Comprehensive Cancer Center, whose research focuses on ethnicity-related variation in breast cancer risk and the evaluation and treatment of high risk patients- Kara Millron, MS, a genetic counselor at the UM Comprehensive Cancer Center, whose research interests include mutations on the BRCA1 and BRCA2 breast cancer genes.This event is made possible through Partners In Research grants R03 NS065493 and R03 NS065491-0 from the National Institute of Neurological Disorders and Stroke of the National Institutes of Health and is co-sponsored by the Michigan Institute for Clinical and Health Research, the UM Health Sciences Libraries, and the University of Michigan Comprehensive Cancer Center. This event is a collaboration with the award-winning documentary series P.O.V. (www.pbs.org/pov).For more information on genetic research and medical testing your may be interested in some of AADL's books and videos about these topics. Articles and current research can also be explored in our research databases MEDLINE and Health and Wellness Resource Center.

Transcript

• [00:00:23.65] DOREEN: I would like to allow each of our panelists to say a few words about their area of expertise, what their clinical interests are, what their research interests are, so that you can best direct your questions to them. So, why don't we start with Lisa.
• [00:00:39.73] LISA: Thanks, Doreen. So as Doreen mentioned, I am surgical oncologist now with a full-time commitment in my career to managing diseases of the breast and focusing on breast cancer. But in the context of that work, we do see a fair number of women who are at high risk for breast cancer and who therefore seek counseling about ways that they can reduce that breast cancer risk. And as you saw from the film, one of the most aggressive ways that you can reduce risk of breast cancer is through prevention or prophylactic mastectomy. So we do several prophylactic mastectomies on a regular basis at the University of Michigan and we have a very prominent breast reconstruction program as well. So I'm certainly happy to answer questions that any of you might have about surgical management of breast cancer itself or about risk-reducing surgery for breast cancer in the form of prophylactic mastectomy and reconstruction.
• [00:01:40.36] DAN: Lisa is being modest. She also has a Masters of Public Health from Harvard and has redefined assessment of risk of breast cancer for African American women. The original breast cancer risk structure was, frankly, deficient in regards to African American women an Lisa changed that and fixed it, which she wouldn't tell you herself but I'm going to.
• [00:02:04.48] LISA: With a lot of help.
• [00:02:06.56] DAN: With a lot of help but it wouldn't have happened.
• [00:02:10.86] So, I'm a medical oncologist. I actually do very little risk or prevention. I do no surgery. In fact, while I got the highest grade in my medical school class for that semester on surgery, I got a bad recommendation because I'm terrible with my hands, as my wife will tell you -- she's in the audience. Lisa won't let me touch anybody with a knife at all. My job is I take care of people once they have breast cancer. My interest in genetics has not been necessarily what causes the cancer. There are a lot of much smarter people than I am working on that. But rather once you get cancer, what you've inherited that changes the way the therapies you take may react.
• [00:02:58.81] So for those of you who have taken medicine at all, and that's everybody in this room, I'm sure, you've noticed that some people get side effects and some don't with exactly the same drug and exactly the same dose. So we've been very interested in trying to figure out what you've inherited that metabolizes that drug or acts as a target for that drug that's different than the person next to you. This is actually a very early field -- we're way behind Mary Clara King and the Who Gets Cancers for What Reasons. But we are beginning, the NIH is funding this sort of work big time and it's going to get bigger. And I think probably in the next ten years we'll be much smarter about how we treat these diseases, as well as how we identify them.
• [00:03:44.75] KARA: I'm Kara Milliron. I'm the genetic counselor that works in the breast and ovarian cancer risk evaluation program at the University of Michigan. I've been there almost 11 years, and I work primarily with families like Joanna's who have breast and ovarian cancer that run in their families. Some come in wanting to be tested, some come in just wanting to get additional information and may or may not be tested.
• [00:04:08.85] My specific research interests are in decision-making, so Joanna's film is quite interesting for me with regards to research. And also, I'm family communication and how families talk about to BRCA1 and the BRCA2 mutation.
• [00:04:27.86] DOREEN: OK, I think we will go on. Joanna, do you want to make any other comments before we take questions?
• [00:04:33.56] JOANNA: Sure. I'm Joanna Rudnick and I am a filmmaker. So when I found out I had the BRCA mutation that's why I decided to make the film. My background was in journalism and my interest was in science and environmental and medical journalism, basically working with physicians to get out their research to the public. So it's very much what we're doing here tonight. So this is great to be a part of this.
• [00:04:59.67] DOREEN: While I'm trying to sort out questions for each of our panelists, are there people in the audience who would like to take the microphone and go ahead and address a question directly? If so, just raise your hand and we'll pass the microphone. A lot of the questions I'm getting are really of genetic risk and genetic counseling questions. So I may have to distribute some of them to folks on the panel who might feel that they should all go to Cara, but I don't think we want to have Cara bombarded with all the questions at once. So I'm going to start with Lisa with a question that you had Lisa. If you could just read the question and then you can answer--. I don't know what your case looks like.
• [00:05:57.93] DAN: It's the additional risk of early mamograms on women at higher risk.
• [00:06:01.99] LISA: OK. That's a very good question. The question is related to risk of mammograms in terms of radiation exposure to the breast. And there is absolutely no reason why any woman should feel that the annual mammograms in and of themselves by radiation exposure will increase risk of any type of cancer. In fact, the radiation exposure that you get from a cross country trip is more in an airplane is more than the radiation exposure you get from annual mammography's starting at age 40 as we recommend to women. It really wouldn't be appropriate to refuse your mammograms on a yearly basis because you're afraid of radiation exposure, unless you'd be willing to decline a free trip to Hawaii cross country on a plane because of radiation fears.
• [00:06:55.55] DOREEN: Go ahead, Dan.
• [00:06:56.50] DAN: So the question I have here is how is it possible to be diagnosed with breast cancer but test negative for the breast cancer gene? That's actually a very good question. I think it's because we've done a relatively poor job of explaining what this is all about. And by "we" I mean the field and doctors in general.
• [00:07:16.32] So most breast cancers, and as Joanne said in her movie, up to 95% of women who get breast cancer get it for reasons other than an inherited defect in BRCA1 or 2, these two genes. If I may explain a little bit in my own terms. We saw the cartoon about the girl walking along and had two genes, one good--. I tell people these genes, BRCA1 and BRCA2, their job in a normal situation is to keep us from getting breast cancer. Every time a cell divides it completely duplicates all of the genes and it makes mistakes. A friend of mine who discovered one of these, not BRCA1 or 2, but a different gene that keeps us from getting cancer, called them spell-checkers, which is something I think we're all used to. When a cell divides it puts itself at rest for a minute and it turns on these spell-checker genes, and they run around and find mistakes and fix them, and then they go back to sleep and then the cell divides again. So everybody gets two copies of every gene, as we saw in the movie -- one from mom, one from dad. It's like getting two legs. So the genes, the spell-checker genes also make mistakes, but when they do it's like hurting one leg -- you can still hop around on the other leg. And other spell-checker genes come from behind and fix them and you're back in business. That's why we don't all get cancer when we're six months old, because there are mistakes made all the time, but there are a lot of these genes that run around and fix other genes, not just BRCA1 and 2.
• [00:08:53.10] But if you're born with either a bad copy from mom or a bad copy from dad -- as you saw there were two men there that were positive and afraid they'd pass it on. It's like being born with one leg. And now if you damage that other leg, you're going to fall down. So all of us are exposed to things that damage genes all the time. As long as you've got two copies of all these other genes whose job it is is to fix them you're OK. But if by bad luck you either knock out both copies, if you've got two good copies, or if you've only got one good copy, it's much easier to knock one out.
• [00:09:28.03] So the point of this is that we know about two genes and breast cancer, BRCA1 and BRCA2. They account for about 5% of all the breast cancers we see. Mary Clara King and many others have worked very, very hard to try to find the genes that may account for the other 95% in association with environmental things that we run into. That's been a very tough nut to crack, not for lack of trying. Somebody just did a study where they looked at up to 20,000 different genes and up to 20,000 people with breast cancer trying to find BRCA3. They actually, out of 20,000 genes found four possibilities. And two of those probably aren't going to pan out in terms of validation. This is really hard work. Mary Clara King is a giant, but it was relatively easy to find BRCA1 and 2 -- it only took her 15 years as we heard, and that was in 1990. We're now 19 years later and we haven't found BRCA3 yet. This is really hard to do.
• [00:10:32.11] So, the average woman who gets breast cancer doesn't get it because she inherited a bad gene, she gets it because she's gotten two good copies knocked out at the same time, and that's why most people who get breast cancer are in their late 50s and 60s, because it just takes a lot of hits over and over and over again, finally, by just bad luck, two things go out at once. Whereas BRCA1 and BRCA2 women, women who are inherited one bad copy, only have to knock one out, so they get their breast cancers earlier and more often. So that's a long-winded answer to that question, but it's a very confusing issue and I think it's important to understand why we don't recommend testing for everybody. In fact, we recommend testing for very few patients. I could not practice without my buddy Cara sitting next to me because she's taught me who I should refer to her, and that's only a handful of patients we see with breast cancer. Everybody else we'd be spending $3,000 to get a bunch of negative tests. So we actually rarely send people to get tested, and the ones we do then we're relatively certain there's a decent chance that they'll be abnormal and Cara will take care of them.
• [00:11:43.85] DOREEN: We're going to move on to the questions I've given to Joanna next. Joanna actually is flying out shortly after we conclude, so we promised that we would have her on her way at 8:45, and if we have more questions where we want to continue, the rest of the panel can stay about 15 minutes after that, and we can continue to take questions. So go ahead, Joanna.
• [00:12:04.86] JOANNA: There's so much that I wanted to comment on the excellent, excellent explanation of how BRCA works. But the three questions, actually, I have here are focused on the Genetic Information Nondiscrimination Act, which we showed in the film was passed and has taken effect. And the Genetic Information Nondiscrimination Act protects anyone who has genetic information from discrimination by your employer and by your insurance company. It does not protect against life insurance. So it's health insurance and it's your employer. So nobody can demand that you actually get a genetic test -- an employer can't test you without your knowledge, that would be breaking the law. If they did then the law actually gives you some resources to actually be able to take up a case against them. So it is comprehensive protection. As I said in the film, I tested anonymous. I was extremely fearful of losing my health insurance. I was very distrustful at the time where health insurance companies were going that I was going to be protected. So I spent a lot of time keeping it out of my health records, which was not a very good idea. Because I'd have to keep going to see my physicians and they'd say, what are you doing here, why are you getting a breast MRI. And I would say, oh, I have the BRCA1 mutation. They'd say why is this not in your file, it's very important that we have this information. I said well, I keep telling you not to write it down. So actually what I learned over the years and then making the film was it is very important to disclose that information to your physician so that they can best treat you. And I do believe that the act is comprehensive in its protections.
• [00:13:41.31] I think that what's so important now is that we get the information out there. A lot of people don't really understand that GINA has passed, that there are these protections. People are still extremely afraid of discrimination, which is a paralyzing factor in terms of getting the information. So I think what great organizations like the Genetic Alliance and other organizations who are trying to get the word out need to do more of is a public service sort of campaign so people know that these protections are there. And the genetic counselors are doing the best job of it and oncology nurses and really educating the public. I think that these protections are indeed there, because it's scary to have that type of information. I remember thinking all of a sudden I have this blueprint of this one sequence of a gene.
• [00:14:22.69] One other thing I wanted to say just because it's not in the film and I always try to say it wherever I go. My family was Ashkenazi Jewish, and there are these specific Ashkenazi Jewish mutation, so everybody would have thought that I would have had one of those, because we had this breast and ovarian cancer pattern. Well, my mother tested negative for that panel. And had she not gone on to get full sequencing of the gene, we never would have found out that we actually had this unique mutation. So it's still a very young field. I wanted to show in the film that there's still grey answers. You can get a "we don't know." You can get a positive, you can get a negative, you can get a "we don't know," which is a variant of undetermint significance. Am I forgetting things now? Uncertain significance, which Martha Haley has in the film. I think it's really important to understand that while Mary Clara King took us one step, and then Myriad took us another step -- that we still have quite a ways to go. One thing--.
• [00:15:22.75] DAN: Joanna, can I interrupt--.
• [00:15:23.98] JOANNA: Sure.
• [00:15:24.48] DAN: --For just a sec. Which is, again, the reason why we don't recommend testing in people who don't seem very likely be positive for the test, because you do get indeterminant significance. You also get mistakes on occasion on any test, and so there's a concern about false-positives. And so we were very careful about whom we refer to Cara and her group so that we're not doing a bunch of tests on people who are not likely to benefit from it.
• [00:15:52.34] JOANNA: I'm going to say two more things and then you've got this wonderful panel here. One thing I know that people have asked here is what decision did I make, because the film is left with sort of a question mark. I recently did see a breast surgeon and I am considering having prophylactic mastectomy. I'm still wrestling with it. And I have to say there wasn't a lot of young breast cancer in my family, so there's this part of me that thinks, OK, maybe it's that there's no young breast cancer. And then I'll meet another woman who has the gene and didn't have young breast cancer and then she got young breast cancer. So I think that they're very difficult decisions to make and I would never discount, but I really tried to show that in the film. But I am leaning towards that I'm going to get my ovaries out at 40. They're tough decisions but I'm really grateful that I have this information, and I hopefully will not suffer the same way some of my relatives and the women in the film have. So in the end I'm grateful. I wish I could sit here and say I did it. I haven't yet, and that's honest. Honest to my story.
• [00:16:57.16] One other thing is someone said, do I ever have a full day where I do not think about cancer? Not lately. And that's the truth. Lately I'm thinking about it a lot, and that's why I'm getting closer to having the surgery. I'm hearing more and more friends of mine diagnosed who have BRCA and it's getting scarier for me. So that's an honest answer.
• [00:17:17.53] KARA: I would just like to make one quick comment about the genetic discrimination issues. Prior to GINA there was a law that still exists, it's called HIPPA, the Health Information Protection and Portability Act. That was passed and it protected people who had group health insurance. So that would be people who got their insurance through their employer or belonged to some other larger group. HIPPA did not cover people who bought their own health insurance, and so that was a big loophole in that law. GINA basically blankets everybody with that protection.
• [00:17:52.31] What I also wanted to say is that I've almost been in this position 11 years and we've tested well over 1,000 people and we'd had no instances of genetic discrimination. Not a single one. And believe me, I would be the first person to get that phone call--.
• [00:18:08.75] JOANNA: I search for it. She knows, I searched for somebody who was in that situation.
• [00:18:13.13] KARA: It's a very safe environment. But unfortunately, as Joanna said, it is still a very large barrier for a lot of individuals. For people who do not have cancer, one of the things that we recommend is before undergoing genetic testing is that they get their life insurance either in place or update their life insurance, because once you have a policy it's yours and it can't be taken away from you. So that's one of the things that we do talk about prior to testing.
• [00:18:41.12] DOREEN: Cara, if you want to go ahead and select a few of yours to respond to and then we'll move onto Lisa. And I'll have to apologize in advance, there is no way we'll be able to get through every single question that's posed here. So if you can select the ones that you think will address the most people's questions.
• [00:18:56.09] KARA: One of the questions here is very interesting. It says why so little attention to male risk. My father got breast cancer at 67 and he passed away from it at 73. And my brother is BRCA2 positive and he developed prostate cancer.
• [00:19:09.36] This is a very, very good question. It's just recently been found that men do you have a cancer risk with these genes. In the past we thought that they did not have a cancer risk, but they could pass it on to their daughters. One of the things is is that the cancer risk is not as high with men, so we're kind of learning our way about how to take care of them, and unfortunately there's not a consensus. But we are starting to draft guidelines and we are still doing education. There still are a lot of people that don't think that men can get breast cancer, and so we're doing a lot of education not only with the public but also with health care providers so that they can look at these family histories and also refer men.
• [00:19:58.14] DOREEN: Lisa, I think we're going to have to read your questions, because we haven't found the reading glasses.
• [00:20:03.08] LISA: I am so sorry.
• [00:20:05.98] DOREEN: So here's the question. I know they say breast tissue is much more dense in your 30s, and thus more difficult to interpret mammograms. However, with the increased of breast cancer diagnosis, shouldn't we consider early mammography screenings?
• [00:20:28.73] LISA: That is a very, very excellent question. Now, in general, as I mentioned before, the recommendations for routine annual mammography screening is for women in the United States to start at age 40. For women that do have some evidence of a familial or hereditary predisposition where you have several members of your family that have been diagnosed with breast and/or ovarian cancer, the rule of thumb that we use is that you should start your mammographic screening five to ten years younger than the earliest age of onset in your family. So, if you have the family members, if your mother, say, was diagnosed with breast cancer at age 38, 40, you should probably start getting your mammograms by age 30. But that's for women with the evidence of hereditary predisposition.
• [00:21:18.48] Also, for women with evidence of hereditary predisposition, we now will frequently counsel women about undergoing breast MIR as an adjunct, as a supplement to mammography. So many of you may have seen all of the literature that's appeared in the press about breast MIR. It's not something that's appropriate for every woman, it is also very costly, as the genetic testing is -- breast MRI is another way to evaluate breast tissue. They cost about $3,000. It can make patients very, very claustrophobic when they're in the machine. It's best suited for women at high risk for breast cancer as evidenced by some prior breast biopsy findings, or as evidenced by a family history. Women with very dense breasts, where the breasts may be more difficult to evaluate on mammography, that is not necessarily going to be a trigger for doing breast MRIs. It may, however, be a trigger or it may indicate a woman who should have a special type of a mammography called digital mammography. And in particular, women who have dense breasts or thick breast tissue seen on the routine mammograms, if they're under the age of 50 they are probably going to be recommended to have digital mammograms on a yearly basis. But not necessarily have mammograms at younger ages, just to have a specialized form of the mammography on their yearly basis.
• [00:22:42.72] Women on population or community-wide basis are at risk for having early onset breast cancer such as African American women. We know that African American women have a younger age distribution for breast cancer, but we don't, nonetheless, we do not recommend that African American women start having mammograms at younger ages. We still recommend that the mammograms start at age 40 and older, unless there's a family history of early onset, young age breast cancer.
• [00:23:12.65] So those are the recommendations based on the best data available from clinical trials, large studies that have documented the appropriateness and the importance of mammograms, and that's what we use at the moment for screening.
• [00:23:29.47] JOANNA: I have one question for Lisa. How available are digital mammograms to the general population? I tried to get one and I was on a waiting list for six months. I still haven't gotten it yet, so I'm just curious.
• [00:23:39.77] LISA: Yeah. There is still some limitation in availability, but it's disappearing rapidly. And probably within the next decade, every place will have converted over to digital mammography, because the film screen mammograms, we just can't support/store them. But there is going to be a lag period while we're going through that transition phase. Most large mammography centers will have at least half of their mammograms done through the digital format. I think that's reasonable to say at the present time. But you should talk to your doctor and with the radiologist who's reading your films to determine whether or not the digital mammograms are more appropriate for you. From the large clinical trials that have been done, conventional film screen mammograms may actually be a little bit better for women age 50 and older with normal density breasts. Digital mammograms may have a little bit of an advantage for women younger than 50 with very dense breasts. But overall, when you look at all women, they're pretty similar, actually.
• [00:24:42.53] DAN: They're also very similar in sites that do a lot of mammography. So our mammographers tell us it doesn't matter to them whether the patient's had it. We're I think about 25% film screen and 75% digital now. We're slowly but surely--
• [00:24:56.75] JOANNA: [UNINTELLIGIBLE] 50/50.
• [00:24:57.72] DAN: Current is at 50/50. But they tell us that in their hands they don't really care if it's done on the digital or on the regular because all they do is read mammograms and they read a lot of them. It's really the reading that's probably more important than the technology, with the exception of the few young women with really dense breasts. That's the one place I agree.
• [00:25:17.75] DOREEN: We have a question from the audience right here.
• [00:25:21.51] AUDIENCE: Speaking of the digital mammogram, did I hear you say that the African American women tend to have more of the thick tissue rather than the dense? LISA: That has actually varied from study to study looking at density of African American women's breast tissue. So I wouldn't want to make a blanket statement because the data on breast density has been variable when you look at African American women, and a lot of it has to do with the age. But in general, we do not make recommendations for African American women to routinely have digital mammograms. We go with the usual screening recommendations that we mentioned, age 40 and older, unless there's a strong family history of early onset, younger age breast cancer. But I did comment that overall, African American women have a younger age distribution for breast cancer. So, if you look at all American women over an average life span of living 80, 85 years, the likelihood of developing breast cancer is higher for white American women compared to African American women. If you look at American women younger than the age of 45, however, the likelihood, the risk of getting breast cancer is actually higher if you're African American. So there's a skewing of the average age of diagnosis towards younger ages in African American women.
• [00:26:47.79] AUDIENCE: So should I be concerned and ask my doctor whether my tissue is dense?
• [00:26:52.85] LISA: Well, it's something -- the breast density should really be determined by your mammogram appearance, not necessarily by what your breast feels like. The breast densities can be surprising on clinical examination in terms of how they actually look on the mammogram film.
• [00:27:08.65] DAN: And I would say, Lisa and I both have patients who are confused. The size of your breasts has nothing to do with the density of your breasts. So I have a lot of women who say well, I've got big breasts, I should have MRI. That's not true at all. The density of your breast is how thick the stuff is inside your skin, and you can't tell from the outside without a mammogram. So there's no way of knowing without an image.
• [00:27:30.94] JOANNA: I just want to say I'm very sorry that I have to leave you all, but you're in wonderful hands. And I wish actually I could stay here because I'm learning so much from the doctors up here and from Cara, always. I want to thank, again, the Ann Arbor District Library and Doreen and Celeste and Tim and everyone on the panel and Molly for welcoming me and for all of you for sharing in this film. I hope you continue to have a good discussion. Thank you.
• [00:27:59.17] [APPLAUSE]
• [00:28:09.39] DOREEN: We will continue with questions because you have a lot, and that's exactly what we wanted to encourage you is to ask questions of our panelists. So, who was last -- was it Cara or Dan over there? Dan's turn. Go ahead, Dan.
• [00:28:27.59] DAN: Well, there are two here. One is for women who have an abnormal gene but want to have children, are there ways to use reproductive technologies to prevent the transmission? To make it clear, this is not like a venereal disease, so it doesn't get passed on because of sex, it gets passed on because the genes are in your cells already. The only reproductive technology is that you would use either an egg or sperm from someone who is not affected. So, let's say the wife of a couple looks like this, to go back to my stupid analogy, and the husband looks like this. What you might do is use ovaries from another woman, who's like this, and the husband, and then perhaps the wife could carry that baby and that sort of thing. I'm not a reproductive specialist in this. To my knowledge we are not--.
• [00:29:27.68] [INTERRUPTION]
• [00:29:44.58] DOREEN: We were told that that announcement does not apply to us.
• [00:29:48.67] DAN: It is true that when eggs and sperm are prepared, they've split off. So every egg is either like this or like that and every sperm is either like this or like that. However, I have not seen technology of being able to pick up the egg that's not affected from the eggs that are from a single woman, have you?
• [00:30:09.97] KARA: We can't specifically do the eggs. We can look at the embryos, called Preimplantation Genetic Diagnosis. That is something that is now starting to be offered, but it is rather expensive and insurance companies will not cover the cost of looking at preimplantation diagnosis.
• [00:30:32.78] DAN: So to be clear, you would have done invitro fertilization in a petri dish, if you will, and then you can pick out now the fertilized embryos that look like this, as opposed to like that, and then re-implant those and have those growing.
• [00:30:52.20] DOREEN: We have another question back here.
• [00:30:54.77] AUDIENCE: This question is for Cara. Is there a special fund, like the B triple C for women who want to get genetic testing, especially African American women or women of minority communities since there is this huge gap in knowledge about what it really means for these populations? Because it's very pricey and cost prohibitive, but for the sake of the science, if people aren't getting tested or can't afford it you'll still have kind of that grey area.
• [00:31:20.25] KARA: Unfortunately, at this time we don't have any funds available to assist patients in that situation. And unfortunately, Myriad has just changed their financial hardship guidelines for patients. And so we really, unfortunately, don't have money at this time. However, I am chair of the Michigan Cancer Genetics Alliance, and it's a statewide committee that is working with the Michigan Department of Community Health. It's a bunch of hospitals and community programs working together with regards to cancer genetics. We're hopeful that in the next two or three years we will be able to have some grant money from the State of Michigan to help women in that situation. But unfortunately, we just don't have it right now.
• [00:32:17.71] DOREEN: I'm going to pose a question that was for Lisa -- I'm having to read it for her again. The film mentioned a one-step breast reconstruction after mastectomy. Why is this not offered after cancer surgery?
• [00:32:31.42] LISA: We actually prefer, whenever possible, to do the single stage breast reconstructions at the time of a mastectomy for breast cancer, also called Immediate Breast Reconstruction. So, breast reconstruction at the time of mastectomy can either be immediate, at the same time as the mastectomy, or it can be delayed months or years later. Whenever possible, again, as breast surgeons, our first bias is in favor of doing the immediate same stage reconstruction, but not every woman is a candidate for it. It could be because of medical reasons that preclude her from having the prolonged anesthesia for Immediate Breast Reconstruction. It could be related to the type of cancer that she has indicating that she would not be a good candidate for Immediate Breast Reconstruction. In some cases, we are concerned about the possibility of needing radiation after a mastectomy and the radiation can be damaging to the reconstructed breast. So some women, if it looks like they will need radiation after a mastectomy, we will recommend that they hold off on doing their reconstruction until after all of their cancer treatment has been completed.
• [00:33:42.53] So there are a variety of reasons why immediate or same stage reconstruction for a mastectomy done for breast cancer might not be appropriate, but that's always our first choice, if the patient is a candidate for it.
• [00:33:55.67] DAN: And Lisa, would you please talk about your opinion of nipple sparing prophylactic mastectomies?
• [00:34:01.75] LISA: Yeah, thanks, Dan, I'm glad you mentioned that. So there was a lot of discussion in the film about the nipple/areola sparing mastectomies. You should keep in mind that that is very much investigational at this point in time. There is anywhere from a 10% to a 20% risk of having breast tissue itself that grows into the skin of the nipple/areola complex, and so there is a very real fear that if a woman is having a mastectomy for breast cancer prevention because she has some hereditary mutation putting her at risk for breast cancer, or if she's having a mastectomy for breast cancer that she might increase the chances of the breast cancer coming back or developing on the first time on the chest wall because of that retained or saved nipple/areola complex.
• [00:34:54.48] There are some types of breast abnormalities where we would feel comfortable doing the nipple or areola sparing mastectomies, but it's rare. Our largest most esteemed academic society for cancer surgery is the Society of Surgical Oncology and we have established some kind of ground rules for performing prophylactic mastectomy, and the prophylactic mastectomy that we support is the conventional mastectomy where the nipple/areola complex is removed with the breast tissue. So, nipple/areola sparing mastectomies are not, at the current time, advocated by the Academic Surgical Oncology world.
• [00:35:42.37] DOREEN: We were just told that the bus is ready to leave to go back to Flint. So, I'm going to let Lisa answer one more question and it's very related to the topic she was just addressing. And then those of you that were on the bus -- we're probably going to have to probably wrap things up in a moment anyway. So let me follow up with this question.
• [00:36:02.49] What is the risk for mortality when a woman with BRCA2 has a prophylactic mastectomy?
• [00:36:09.14] LISA: From the prophylactic surgery?
• [00:36:10.98] DOREEN: No. I guess the question would be from getting cancer following the mastectomy.
• [00:36:15.85] LISA: Thank you very, very much. That's an excellent, excellent question. The prophylactic mastectomy reduces breast cancer risk by about 90% of whatever that woman's baseline risk is. So it's not 100% effective -- extremely important to remember. In the case reports that have appeared in the literature of women who go on to develop breast cancer despite having the prophylactic mastectomy, that breast cancer can develop one the chest wall because the microscopic breast tissue on the skin of the chest wall, in the underarm area, or even on the muscle surface, and it can happen within a few months after the surgery, it can happen several decades after the surgery. It's uncommon, but it can happen.
• [00:36:56.06] There are no long-term -- there are no studies that directly compare women with hereditary breast cancer risk who have either undergone the prophylactic mastectomy or not, because it would be extremely difficult to conduct such a clinical trial. But with the best data available, either looking back at women who have had the surgery or by doing statistical modeling to estimate longevity gain by having a prophylactic mastectomy, we estimate that you gain about four years of longevity if you have a prophylactic mastectomy by age 30, if you're a BRCA mutation carrier. If you are a BRCA mutation carrier and you have a prophylactic mastectomy at age 60, you probably don't gain so much in terms of life span by virtue of reducing your breast cancer risk, because if you haven't gotten breast cancer by the age of 60, despite the fact that you have the mutation, you probably have other genes protecting you against breast cancer, or you've had other things in your life that have somehow modified your risk and you face other risks to your longevity by age 60. So those are the kind of numbers that we use when we counsel women about prophylactic mastectomy because of high risk for breast cancer.
• [00:38:11.31] DOREEN: I think you can all see just how complicated and personal a lot of these answers are. There are some cards that I received that have very specific questions that wouldn't be as of much interest to the rest of the audience, so my apologies if I'm not circulating those. We're going to really try to focus on the questions that will meet the questions that most of the audience may have.
• [00:38:32.95] Cara, you had a number of them. Do you want to pick one that you think is of general interest?
• [00:38:36.81] KARA: Sure. One of the questions was a very good question. How do you deal with a mutation of uncertain variance? Wait or consider it as a positive test result.
• [00:38:47.48] DOREEN: Thank you everyone from Flint for coming and joining us this evening. We really appreciated your participation.
• [00:38:54.58] KARA: When we look at how often we see variance of uncertain significance, it's about 7% of the time across the board. But when we look at specific ethnic backgrounds, the rate of variance of uncertain significance can increase. For example, African American women, they have a 15% risk of having a variant of uncertain significance if they undergo BRCA1 or BRCA2 testing. So, we still have a lot of work to do. One of the things that we do--.
• [00:39:26.34] [INTERRUPTION]
• [00:39:38.10] One of the things that we try to do is we try to establish which side of the family the variant could be coming from. If it's coming from the family side that has a lot of the cancer diagnoses, that gives us a little bit of information that this could potentially be something that is contributing to cancer. We also try to look at how often the variant has been seen. And also, if the variant's been seen with a known change that definitely does cause cancer. Because we know that we all need at least one normal copy of BRCA1 or BRCA2 to grow and develop as a baby. So if we have seen a variant in addition with a known mutation in BRCA2 or BRCA1, it reduces the likelihood or the chance that that variant is something that does contribute to cancer. So, we are doing a lot of work on variance of uncertain significance. We have had a lot of reclassification in the last six months. So we are learning, but we still have a long ways to go. And it is, unfortunately, still a risk for patients when they undergo the genetic testing is that there is a 7% to 15% chance that we could find a gray area result.
• [00:40:52.90] DAN: Do you remember the little poem that Mary Clara King had up about the cat -- I can't remember what it was -- and then they just took out one thing and everything collapsed and was nonsense. What Cara's talking about, for example, you could spell tic t-i-k or t-i-c. So let's say that t-i-c is the right way to spell it, but you could mutate the c to a k and it still spells tik. And that's the problem is that you're going to find changes in these -- these enormous genes have thousands of letters, and one letter may be changed to another and that may or may not actually change the function of the protein the gene is making. So it's like changing the k to the c. On the other hand if you change the k to an e, now instead of tik it's tie -- so you know that's a completely different word. And that's part of her problem is trying to sort it out which of these we know are bad versus which of these we know are completely normal versus this gray zone where we see things that may or may not be bad and they haven't been described, but maybe in your family, you're the first family to have that and it's bad but we don't know it yet. Is that a better way -- not a better way, but a good way--.
• [00:42:03.65] KARA: No, that's a very good way.
• [00:42:05.09] DAN: Because I get confused on this, too. So I always go over to Cara and say what is that all about?
• [00:42:10.13] DOREEN: Is there anyone else still in the audience for the bus to Flint? I see your coordinator looking around the room. OK. We don't want anyone missing the bus. I'm going to actually ask a question aloud that I received on a card from someone in the audience to all three of our panelists, because it really sort of summarizes one of the reasons why the NIH funded this particular grant to myself and Celeste and Mich-R in the library, which is to really encourage and engage the community in a knowledgeable way about clinical research. So the question that we received was what clinical research studies are going on in breast and ovarian cancer at the University of Michigan? And maybe each of you can touch on studies that you're involved in at this time.
• [00:42:53.41] DAN: So this is music to my ears. All three of us are very much involved in a number of trials. Part of our job is -- our first job is to take good care of patients. I personally think we do a wonderful job of that, because we have great surgeons and great genetic counselors. But our second job is to take better care of the next group of patients than we're taking care of now. This is going to be a long-winded answer on purpose.
• [00:43:19.85] The advances we've made in breast cancer over the last two and a half decades that I've been in the field are just unbelievable. So when I came in the field, radical mastectomies were still done and modified radical mastectomies were the treatment of choice. When I came in the field, the issue of giving chemotherapy to prevent a recurrence and the issue of giving hormone therapy to prevent occurrence was quite controversial and far from proven. When I came in the field, everyone who got chemotherapy got terribly sick. We had to put them in the hospital to knock them out, basically. And when I came in the field, there were a number of other things that we do routinely now that weren't even thought of, like therapy R2 and therapy against new blood vessels. All of those--.
• [00:44:00.51] [INTERRUPTION] All of those things now have been incorporated into routine clinical care because of clinical research and clinical trials. By the way, there was also not even a concept that there would be a gene that we could actually find that would help predict who's going to get cancer or not.
• [00:44:19.08] So we've seen mortality from breast cancer in the Western world, in general, where these things have been applied coming out of clinical trials and then applied in the routine setting. We've seen breast cancer mortality just careen downwards so that a woman who lives in the Western world in 2009 actually has a lower chance of dying of breast cancer than her mother or grandmother. We're lower than we were in 1950. It went up to about 1980, plateaued, and then dropped back down again. All because of clinical research. When we do clinical research we do two things. Our first thing that we do is we say what's the best care for this patient in front of me, regardless of what the trials are, what's the best care for this patient. And then can we apply that care within the context of a trial. If it's not right for that patient, she's not on trial. If the patient doesn't want to be on a trial, she's not on a trial. But if we can, if we can take good care of that patient, and learn more and take better care of the next patient, then we've accomplished two goals, both of which are very important. And again, you can tell I'm passionate about this because I think we do a pretty good job of it.
• [00:45:24.23] The specific things we're doing, I could roughly run over. We've got studies related to risk and prevention that Cara and her boss, Dr. Milliran are running--.
• [00:45:33.47] KARA: Dr. [? Meriver. ?]
• [00:45:34.62] DAN: Oh, Dr. [? Meriver -- ?] sorry, you're--. I'm in a clinic all day, give me a break. And then we have studies of better ways of doing surgery, mostly fewer ways of doing surgery. And one of the things--.
• [00:45:48.70] KARA: We want to put Lisa out of business.
• [00:45:51.45] DAN: Well, I was just going to say, one of the things we have to really tip our hat to is that Lisa's predecessors and Lisa and her generation now have spent a lot of time trying to figure out how to do less of what they do. And each of you probably is in business or works somewhere, and if you think about it, would you actually do research to prove that what you do is not necessary? That would be pretty hard to do and they've done it. So I have enormous respect for the people who have done that.
• [00:46:16.87] And then in my field, we do a lot of research on better ways of giving chemotherapy, ways to identify people who don't need the chemotherapy. So again, we're trying to do what they did a generation ago, which was to peel chemotherapy off and not give it to a bunch of people or it won't work. And better targets and better ways to prevent breast cancer recurrence without chemotherapy. So, anti-estrogen therapies, anti-HER2, anti-angiogenesis, and now there's some new targets. Many of you have probably heard of the so-called triple negative breast cancer. These are people who have cancers that are not positive [? estrogen ?] receptors. They don't estrogen, they're not positive for this HER2 molecule. And there's been a lot of concern that those women are being left behind, if you will, because there's not some --. And in fact, in the last six months there now is a specific target. You're going to hear a lot of exciting stuff in the newspapers in the next six to twelve months about treatments directed for that target, for that group of patients. So there's really quite a bit going on.
• [00:47:16.89] DOREEN: In addition to sort of the standard type of clinical trial or clinical research that's been referred to, there's also a lot of research that goes into the psychological and social health of women facing risk for breast cancer or who have had breast cancer. I know that Cara and [? Dr. Meriver ?] have a lot of studies that deal with that aspect. And Cara, do you want to mention any of those?
• [00:47:38.59] KARA: Yeah. Looking at decision-making in a lot of our patient population, we're also looking at does the intervention of genetic counseling help with perception of risk and does it help the patient make the decision that they feel most comfortable with. We're also looking at reproductive decisions that BRCA1 and BRCA2 mutation carriers make and their thoughts and feelings about prenatal diagnosis as well as pre-implantation genetic diagnosis. And we're also looking at how often we find ovarian cancer and breast cancer when patients undergo prophylactic surgeries. And I'm very lucky, I mentor a bunch of genetic counseling students and they do research projects as part of their degrees. So we've been very blessed. A lot of the research projects have been the ideas of actually genetic counseling students. So it's been nice.
• [00:48:37.57] DOREEN: And I know that Lisa's research actually expands beyond the borders of the United States and reaches into populations in Ghana . Lisa, would you like to comment on that research?
• [00:48:47.50] LISA: So, Dr. Hayes, in addition to being an incredible doctor, is our foremost breast cancer researcher at the University of Michigan and renowned internationally, which is why he's won so many awards. I really can't add a whole lot to what he's already talked about in terms of ongoing research. But I will comment on what Doreen mentioned. We are looking at the issue of African ancestry, in and of itself, potentially being associated with a hereditary risk factor for developing certain types of breast cancer, such as the one that Dr. Hayes mentioned, the triple negative breast cancer. So my work involves studying the breast cancer burden of women from Africa, looking specifically at women from Ghana, because Ghana on the western sub-Sarharan Africa is a location where a lot of the slave colonies were and so there's probably shared ancestry between African Americans and African women. But if we can identify a heritable risk factor for these triple negative breast cancers by studying the breast cancer burden of women from Ghana, it obviously will be quite meaningful for women around the world, because the triple negative breast cancer account disproportionately for the breast cancer deaths that we see in women around the world, regardless of ancestry.
• [00:49:59.57] Another very exciting surgical research program that will be available at the University of Michigan very soon is going to be evaluating cryoablation or freezing of breast tumors. This is a national study that will be ongoing, conducted by the American College of Surgeons Oncology Group. But one of my partners, Dr. Michael Sabel is one of the world's leaders in cryoablation or the freezing of breast tumors, and so he will be in charge. He'll be running a lot of this cryoablation program for this national study.
• [00:50:33.67] DOREEN: Last question, go ahead.
• [00:50:34.79] AUDIENCE: [INAUDIBLE].
• [00:50:48.28] LISA: The blue dyes for the sentinel nodes?
• [00:50:50.57] AUDIENCE: [INAUDIBLE].
• [00:50:53.28] LISA: So, I think probably what you're talking about is the sentinel node biopsy -- technology to avoid the axillary lymph node dissection in breast cancer patients?
• [00:51:01.33] AUDIENCE: [INAUDIBLE]. into the tissue area, so you can remove 95% or 100%.
• [00:51:21.02] LISA: So there are various programs underway to look at injections into the breasts to either improve lumpectomy performance, or to improve ways of finding the most important lymph nodes that drain the breast in the underarm area. The one that we use most commonly, you can actually consider it standard of care now, is the lymphatic mapping and sentinel lymph node biopsy procedure for breast cancer where we inject a blue dye and a radioactive material in the breast and then identify the lymph nodes that have taken up those substances. And it allows us to avoid the full axillary lymph node dissection in breast cancer patients. And the axillary lymph node dissection is the operation that puts women at risk for lymphedema, the swelling of the arm. But along the same vein as that lymphatic mapping technology are a whole host of other technologies that follow the same format but are aimed at using those mapping agents to accomplish different things. Some of them involve injections of radioactive material into the breast to try to improve the performance of the lumpectomy itself by helping you define how wide an area of breast tissue needs to be removed. Some of them involve these injections of fluorescent or special types of colored agents into the breast to improve the ability to perform the lumpectomy with negative margins.
• [00:52:50.70] DOREEN: I think we're going to have to draw our evening to a close. I want to thank our panelists for coming here after a very long day.
• [00:52:58.11] [APPLAUSE]
• [00:53:05.25] [MUSIC]