Breast Cancer Prevention

Speaker 1: Welcome to Bench to Bedside, a weekly series of live conversations about recent advances in cancer from the research bench to treatment at the patient's beside. And now, your host and the director of The University of Kansas Cancer Center, Dr. Roy Jensen.

Dr. Klemp: Good morning and welcome to Bench to Bedside. I'm Dr. Jennifer Klemp, the co-leader for Cancer Prevention and Survivorship at the University of Kansas Cancer Center. I'm sitting in for Dr. Roy Jensen, who's off on another exciting assignment. My guests today are Dr. Anne O'Dea, who's the Medical Director for Breast Cancer Survivorship, and Dr. Lauren Nye, who's the dedical direct for Breast Cancer Prevention. They are both medical oncologists here at The University of Kansas Cancer Center. Thank you both for taking the time to join us today.

Dr. Nye: Thank you.

Dr. O'Dea: Thanks.

Dr. Klemp: Great. Our discussion today is going to revolve around what does it mean to be at high risk for developing breast cancer? We have improved understanding of breast cancer risk factors. And now, we can more closely look at an individual's personal and family history and other risk factors to help determine what their risk is for developing breast cancer. As a result, we provide patients with an individualized risk assessment along with a variety of options, including increased screening, lifestyle modification, preventive surgery, and access to clinical trials. So, Dr. Nye, can you give us a little bit of background as to if a patient is out there saying, well, what does it mean to be at high risk for breast cancer?

Dr. Nye: Absolutely. So, we should probably start with recognizing that breast cancer is common. One in eight women will develop breast cancer who are at average risk, so that's almost a lifetime risk of 12% of developing breast cancer. In a woman who is high risk, that risk is somewhere around 20%, or almost double the average woman's risk of breast cancer. Some risk factors that may make you high risk can be a strong family history of breast cancer, especially if it's in a first or second degree relative that had breast cancer before menopause. So that is like your mom, your sister, your daughter, your aunt, your grandma. If there is a male breast cancer in the family, if there is a known genetic mutation in the family that's associated with high risk of breast cancer, or if you've had a breast biopsy that's associated with some high risk features. And lastly, if you have really high breast density that's been shown to increase your risk of breast cancer.

Dr. Klemp: Okay. What if don't know my family history? Dr. O'Dea, if I present in your clinic, what do you do if I just don't know or we don't have a good understanding?

Dr. O'Dea: Yeah. That happens not uncommonly. So what we have to do is look at the constellation of other factors that we do know. So we look at the age of menarche, the age of menopause, use of estrogen containing drugs, those sorts of things that may confound an additional risk outside of family history. We can also consider the possibility of genetic testing, depending on that patient's individual situation.

Dr. Klemp: And if we did decide to do genetic testing, I think one of the things that's so common right now, especially I feel like everyone for Mother's Day, you saw the ads, well, what's your heritage and where did you come from? So, what's the difference between the kind we may see on TV and the types of tests you would do? And, how do you decide if I'm the best person to do it in my family?

Dr. O'Dea: Do you want it?

Dr. Nye: I can start.

Dr. O'Dea: Okay. Go ahead.

Dr. Nye: So, that is direct to consumer testing. The test that you can get, hopefully, for Mother's Day that tell you your ancestry and maybe where your relatives are from can be really fun. But they are not for cancer genetic testing, which is what we're talking about today, and what Dr. O'Dea was hinting at. Cancer genetic testing is available through some of those direct to consumer kits that you can get, but I would not advise taking this method to test to see if you have genetic mutation. That should really be in the setting of genetic counseling so you know what you're getting into and you know what the results mean when they come back.

Dr. Klemp: Great. What type of individual presents in the clinic that you would recommend testing for?

Dr. O'Dea: If we see red flags that there might be a gene present within the family. So that can be some of the things that Dr. Nye referenced earlier. For example, the presence of breast cancer in a male, the combination of breast cancer and ovarian cancer in the same sort of family, multiple first or second degree relatives over many generations. Those are all things that we look at because we also look at the age of diagnosis of each individual that's been affected by cancer we know that patients who have these hereditary mutations in their family are more likely to be diagnosed at younger ages. So when we see breast cancer diagnosed in the pre-menopausal age range, that's definitely a red flag to us that we might need to look closer at that family.

Dr. Klemp: What is it, just so people understand a little more, what does genetic testing consist of? Do I spit in a tube? Do you draw some blood? And what are you actually looking for when you send it off to some magical lab?

Dr. Nye: All of the above. You can have your blood drawn. Some of them, you spit in a tube and it gets sent off to a lab. Nothing really magical, very science based. It takes around three to four weeks to get the results back. Those results come back to myself or Dr. O'Dea or a genetic counselor. Those results can be a negative result, meaning we did not find a genetic mutation; a positive result, we did find a genetic mutation; or something called a variant. If you get a negative result from your genetic testing, it doesn't mean that you're at average risk for breast cancer, however. It just means that you don't have a genetic mutation that increases your risk for breast cancer. So you very likely are still eligible for screening and prevention measures for high risk women. A positive mutation means that we did identify a mutation that's probably present in your family that increases your risk of breast cancer. And those mutations can be associated with other cancers as well that we probably should be screening for. And then the last possibility is something called a variant. A variant means that your DNA is spelled a little bit differently and that's what makes you different from me, different from Dr. O'Dea. But we don't know if it increases your risk of cancer. That's something we keep an eye on and, over time, it may get reclassified as a yes, you have a mutation, or no, you do not.

Dr. Klemp: So, when you think about a patient who comes to see you to the high risk clinic, they probably don't have a diagnosis of breast cancer and maybe they don't have a mom or a cousin who had breast cancer available for testing. A lot of those patients, it sounds like, will probably stay at high risk for breast cancer, then. You're not necessarily going to move their risk up or down. They kind of stay right where they walk in the door. It seems like that could be a sort of not really understood, probably, by the general population.

Dr. O'Dea: Yeah. I think it's important to help patients understand accurately what their risk is. I think ... I don't know if you feel the same, but I think most patients tend to actually over estimate what that risk is. They sort of ... especially if they have a strong family history, they tend to sort of feel like it's inevitable, that it's just a matter of time until they're diagnosed with breast cancer. So we like to start with them from a position of empowerment, helping them understand accurately what their risk is, and then, what are the modifiable things that we can work on to get their risk as low as possible. And then, if they are at elevated risk, what are the ways that we can surveil them more carefully, rather than just a routine mammogram once a year that's available to the general public?

Dr. Klemp: Great. Great. So, if everyone out there is just joining us, we're talking about what does it mean to be at high risk for breast cancer. Please feel free to share this information with your friends and family. And also, don't hesitate to reach out and ask us any questions. You can use the hashtag benchtobedside. So, kind of building on what Dr. O'Dea just said with screening and options. Let's say that high risk patient goes through this comprehensive risk assessment and may or not include genetic testing. What are the game plan, or how do you put together a plan for next steps?

Dr. Nye: When a patient comes to the high risk clinic, they start out with this really comprehensive risk assessment with all the details Dr. O'Dea alluded to. We talk about genetic testing if we think it's indicated. And then we leave them with a plan. That plan is a surveillance plan. So what we recommend for breast imaging. That can include the annual mammogram with the 3D mammogram, as well as the possibility of additional ultrasounds or breast MRI annually for screening. For prevention, there's a lot of tools out there to reduce a woman's risk. Most patients, I would say, are very surprised at how much we can reduce their risk, both with lifestyle modifications such as exercising, getting your weight to a healthy body weight, and limiting alcohol. But then, also, there are medications that you can take to substantially reduce your risk of breast cancer.

Dr. Klemp: What type of patient, then, would ultimatetly need preventive surgery? I think that when you think about these different levels of risk, screening, preventive medication, lifestyle, that seems to be something like all of us should probably at least kind of consider where are you. But, who, then, ultimately does preventive surgery?

Dr. O'Dea: I think that's something that's in the press, especially a lot lately with Angelina Jolie's diagnosis of a BRC mutation, which she inherited from her mother who passed from ovarian cancer. So, there was a lot of press about that. And women, I think, became very interested in their own genetic status and their family history after that. And of course, she chose to do prophylactic or preventative surgery, so removal of the breast tissue, of course, with reconstruction, which is done with a reconstructive plastic surgeon. The patients that really need that are sort of fall in our highest risk category because going through a surgery like that, putting your body under the risk of anesthesia, the risk for post operative complications, like infections and other things, the risk for developing breast cancer over the course of one's lifetime has to be high enough to sort of make that justifiable. Certainly, the patients with what we call high penetrance genes. What we mean when we talk about penetrance is, what is the likelihood if you possess a certain gene, that you ultimately end up being affected by the disease, in this case, breast cancer? For example, with a BRCA1 mutation, there are studies that would say it could be as high as 80% lifetime risk of developing breast cancer. Well, if I have an 80% chance of developing a life threatening disease, that may be something where I choose to surgically remove the breast tissue with reconstruction and then have ongoing surveillance with a physician. So it would really be those highest risk patients that we worry just even extra surveillance may not be enough for them.

Dr. Klemp: So that cost benefit really has to be there?

Dr. O'Dea: Absolutely.

Dr. Klemp: So that's really reserved to that highest risk group? If you also have a patient, because I know that now we do different things when it comes to even biopsies. It's not like the surgeon's taking a patient to the operating room for a biopsy anymore.

Dr. O'Dea: Well, we hope not. But, unfortunately, we do see that happen occasionally, still. And today, in 2018, it's definitely far outside of the standard of care now. Minimally invasive biopsies are really the standard. What that means is that we don't use a surgery, we don't use a scalpel to remove an unknown entity, whether it's a mass or a cyst or whatever it might be. We use basically a minimally invasive technique that is done by either a surgeon or a radiologist who is trained in that procedure. So doing that, you have less risk of disturbing the blood supply so that if, in fact, this is a cancer, ultimately, that is biopsied, you haven't disturbed the lymphatic drainage, the blood supply and drainage in that pattern, so that ultimately, when you do need to have a surgery to definitively remove that cancer, it can be done appropriately with a lot of planning to minimize the risk that you might need to have a second or third surgery.

Dr. Klemp: Mm-hmm (affirmative). So, when they take that sample, then it's read by a pathologist. Tell me a little bit more about what our process is here at KU. How does that high risk woman or a woman with a suspicious finding on her mammogram, how does her sample get worked on at KU?

Dr. Nye: Any woman that comes through our breast imaging department and has abnormal imaging or needs a breast biopsy, if that biopsy comes back and it is not cancer, which most of the time it comes back and it's not cancer, but it is some benign pathology which means it's not necessarily called normal breast tissue, it is reviewed by our pathologist, our breast radiologist, our breast surgeon, as well as a breast medical oncologist. We all sit together and make sure that what they found in the tissue, what the pathologist sees under the microscope looks like what the radiologist sees on their mammogram or their MRI. That's called concordance. So, if what they see on the slide looks like what was seen in the breast on the imaging, then we say we probably removed everything and this doesn't warrant further surgery. Many times, what we've been doing is lowering the ... Or, increasing the threshold to take a woman to surgery. So, we're decreasing the number of women that have to have surgery to remove what turns out to be benign.

Dr. Klemp: So, you have a special sort of tumor conference just for these benign breast biopsies? [crosstalk 00:14:13] that seems like it's probably pretty unique, not only in the region, but even probably nationally.

Dr. Nye: It's one of the great things about our breast program, is that we handle breast cancer with the utmost multi-disciplinary approach, but also benign breast disease in the same manner.

Dr. O'Dea: It just can't be emphasized enough how critically important this is, because when we're seeing patients in the high risk clinic or even when we're seeing patients that, unfortunately, make it to us as a patient that's now been diagnosed with cancer, sometimes when we go back and we look through their history, we may see that they had a biopsy five years ago which actually showed some changes and were indicative that the conditions were right for a breast cancer to develop or even sort of precancerous changes that maybe weren't managed as optimally as they could have been. If that had been managed optimally a few a years ago they may not have ultimately gone on to develop and actual breast cancer. So, we believe that the handling of the benign, or noncancerous, breast lesions is just as important, if not almost more so, than the patients that ultimately turn out to have cancer. If there's a diagnosis of cancer, it's sort of very black and white and we proceed down a certain pathway. But the patients that are found to have a benign lesion, it takes a very skilled group of multi-disciplinary physicians to work together to make sure that that is handled in the best way possible for that woman's health.

Dr. Klemp: I would think that with that group of high risk patients that does have to come back for more frequent screening, it's likely that they're going to need follow up because the more you get screened, the more likely you're going to need some sort of follow up. But having this level of scrutiny is really going to minimize unnecessary follow up, at least it sounds like it could do that. Have you found that to be the case?

Dr. Nye: Yes. And just going back to those lesions that we were talking about. That's something called atypia or atypia with hyperplasia or lobular carcinoma in situ. So if you've ever had a biopsy with something that says that, that is something we see in our high risk clinic and help you understand what it is and how to reduce your risk of that becoming a breast cancer. We're even discussing some of our ductal carcinoma in situ cases in that conference now, because there is a global approach to try and decrease surgery for those women, as well.

Dr. Klemp: Right. So it's really cutting edge of how you're managing patients before they get to that invasive [crosstalk 00:16:40] hopefully, we prevent them from getting there.

Dr. O'Dea: Absolutely. We have some clinical trials, which are available for patients. I know I just saw a patient in a second opinion who was diagnosed with what we would call a Stage 0 or situ ductal carcinoma. She was a patient that had some other health issues. She really very strongly felt that she did not want to have surgery for this lesion. Looking back on her mammography, we could see that this lesion had been present for at least five or six years and really hadn't changed substantially over that time period. So we felt like she was an ideal candidate to participate in a clinical trial where we're doing a more aggressive surveillance approach with her so that she can avoid surgery. And of course, we can always move towards surgery if that should become necessary in the future.

Dr. Klemp: That's great. So having options is really important, also, I think for patients when they're trying to weigh out that cost benefit ratio.

Dr. O'Dea: Mm-hmm (affirmative).

Dr. Klemp: So, if you're just joining us, we have Doctors O'Dea and Dr. Nye here talking about what does it mean to be at high risk for breast cancer? And, hopefully, you can join us every Wednesday at 10 o'clock for our Bench to Bedside. We are almost done today because we've had such a great dialogue and time seems to fly when we talk about topics that are very important and passionate to us. We do want to thank you all for your time. Check out the hashtag benchtobedside and please join Dr. Jensen every Wednesday at 10 o'clock here at The University of Kansas Cancer Center. Thank you very much.