Doctors must weigh numerous factors as they seek to identify and manage patients at high breast cancer risk. In this half-hour presentation, breast surgeon Karen Goodwin, DO, breaks these tasks down, not only clarifying elements such as family and personal history but offering usable risk-assessment tools as well as guidance on when genetic testing is appropriate. She covers preventive steps ranging from lifestyle modifications to risk-reducing drugs to surgery. Bonus: a look at other hereditary genetic mutations and what they actually mean.
We're going to talk today about breast cancer, risk assessment and risk reduction. And the three main things that we're going to talk about is how do we identify patients that may have a family or personal history of atypical or cancerous lesions that may put our patients at risk for breast cancer? We're going to identify patients who may meet the criteria for genetic counseling and testing. And what does that mean? And then we'll talk about how to incorporate risk reduction education into overall patient health, education and care. So the first thing I just always like to show when we're talking about breast cancer risk and sort of why is this important is this is the American Cancer Society's 2021 estimations for cancers in the United States. And, as you see, breast cancer is the number one cancer in females and the number two cause of death from cancer in females. So they estimate about 281,000 women will get breast cancer in 2021 we all know that about one in eight women in their lifetime get breast cancer. So, you know, really starting to think more towards Not only how do we diagnose, how do we screen? How do we find these breast cancers? But also how do we figure out who's at risk of getting breast cancer? And how can we mitigate that risk or bring that down? Okay, so, um, so just some non familial causes of breast cancer. You know, we are learning a lot about lifestyle factors, obesity and a high caloric diet with insufficient exercise. Does show that it increases our risk of getting breast cancer and alcohol intake. Certainly we know things like reproductive age. What age where we when we got our first period, when we went through menopause, when we had our first life birth. And did we have Children? Certainly. If we've had a personal history of a high risk breast lesion that does put us at higher risk, there are a lot of studies coming out about environmental exposures and occupational hazards. We know that D. E. S given to women in the 19 forties to 19 seventies increased the risk to those babies that were in utero. Certainly, radiation through like mental radiation for lymphoma, can increase our risk and prolonged hormonal therapy, including bio identical and really, we think about more than three years of combined estrogen progesterone that will increase our risk of getting breast cancer the longer that it's taken. But we also know that we have risk due to our family history. And about 10% of all breast cancers are related to a pathogenic germ line variant in one of several genes. So most of these are defective genes on autism. So non sex chromosomes, which means that breast cancer genes can be passed down from both your mother or your father. Um, and when we talk about family members, we really go quite a ways back. We really talk about 1st, 2nd and 3rd degree family members that we have to kind of consider, as we all probably know, the most common breast cancer gene defects are on B. R. C, a one and B R C. A. Two. But the more we learn about genetics, the more we recognize other genes that can also elevate our risk for breast cancer and other cancers. And just to point out, not everyone with a defective breast cancer gene is going to develop cancer. So as you'll hear later, what are some ways that we can, you know, decrease risk. Surgical options are not always the patients first choice, depending on kind of personal risk aversion or risk assessment. And then Ashkenazi Jewish heritage also increases our risk. And we know that about one in 40 women that are Ashkenazi Jewish have the B R C, a mutation compared to about one in 400 non Ashkenazi. So that's something important to ask about. So how do we figure out what our risk is? Well, there's a lot of risk assessment calculation tools out there that we can find on the Internet. Um, I would say the most common are the Gail model and the Tire acoustic model, and there's a lot of other, less commonly used models. And so how do we decide what to use and why would we use it? Well, this is the Gail model, and here's the website where you can find it, and this helps us estimate the absolute five year risk and lifetime risk of breast cancer of a patient. Um, it is not super comprehensive, so it does take into account the things listed here, but it is not comprehensive for family history and it's not really used to estimate what is the risk of someone having a genetic mutation? It's more helpful in assessing the role for who might benefit from something called chemo prevention, which we'll talk about in a minute. And that really is. If the five year Gail Risk is greater than 1.67% patients can can benefit from chemo prevention. I would say the one that we probably use most commonly is called the Tire Acoustic Model, and this is the website where you can find that. And this is just a snapshot of what the tire acoustic looks like when you pull it up, it asks for things such as the woman's age, monarchy, their height and weight. Um, have they had babies? And at what age have they had prior biopsies? And where are they in their menstrual cycle? Are they pre peri and postmenopausal? For a woman who has been getting mammograms? You can also add in their breast density. And as most of we of us know, when you look at a mammogram, the radiologist will give us what's called a bi rads classification of their density, so you can add that in. In addition, because we know that patients that have heterogeneous lee or or extremely dense breast tissue may have a slightly increased risk, Um, we This also allows us to add a lot more extensive family history than the Gail model. So it takes into account our grandparents. Our aunts are half siblings or cousins. It will take into account whether or not a patient has had genetic testing and also are the Ashkenazi Jewish. And have they taken hormone replacement therapy? And for how long? So this will create a family tree. And then, when you hit calculate risk. You're going to get something that looks like this where it will tell you the general population of someone your patient's age looks at. What is their tenure in lifetime risk? And then what is your patients? Tenure in lifetime risk? And also this is really helpful to kind of gauge. Do we think this patient may be at risk of having a break of mutation, and should we consider genetic testing for someone like this? Now we use sort of a lifetime risk of 20% as a cut off between moderate risk or lower average risk to high risk. So when we talk about who is at high risk, we're really talking about. If we do entire acoustic model, who's above that 20% mark now, the only thing I will say is these are all estimates. These are all statistical estimates. They are not perfect. And there are times depending on the individual patient, where one of these may under or overestimate risk. And sometimes we do see that. So sometimes we'll calculate both and see where do we sit? And the numbers are not going to be the same, But we can kind of talk about the range that we're seeing their risk to be in. So what do we do if we find someone that's higher than 20% lifetime risk? What we call, we recommend that they consider high risk screening. Well, what this means is breast self awareness, which I know is quite vague. We used to just say breast self exam, and I would say that's still part of this, where you really like to empower these women to know their body, know what your normal feels like? Feel this with your doctor so that you can kind of point out these are densities. This is what normal density feels like and sort of describe what they might be looking for, and also talking about things like It's important to look at your breast in the mirror and move your arms all around so that you can see if something's pulling in or retracting or looks different, even if you can't feel a solid mass clinical breast exam every 12 or 6 to 12 months, starting when you identify that, they're at high risk. And this says 6 to 12 months because you know you might do a risk assessment on a 20 year old who's first family member had breast cancer at 35? Well, you may not need to be doing a breast exam for that patient every six months, starting at 20. But when they get closer to the age of the youngest family member, you may up it from the every annual visit to every six month visit. We do recommend annual mammograms for screening that is still our gold standard, and we generally recommend, starting 10 years prior to the youngest family member who had breast cancer but no earlier than 30 years old or age 40 whichever came first, so if their first family member was 35 we would start them at 30. But if their first family member was at 65 we would start them at 40. And we also add an annual screening MRI, and this also starts 10 year prior to the youngest family member. But with an MRI, we can start a bit earlier than mammogram because we can see through those densities a bit better, since we use contrast with the MRI so no earlier than 25 or age 40 whichever comes first. And then we really need to be considering who sits at high risk for a genetic mutation and who might qualify for genetic testing. And we're going to talk about that a little bit longer later. So going back to that chemo prevention, really, what we're talking about here is using drugs like tamoxifen or the aroma taste inhibitors for risk reduction. Now, this is not the perfect answer for everyone, but it is something we should be having conversations with patients who are found to be at high risk, that we have lots of trials that show that five years of tamoxifen or raloxifene or even now, the aromatase inhibitors. XMS Dana Remedies can reduce the risk of breast cancer by somewhere around 52 up to 65% for XMS staying in that step one study Now. More recently, we know these drugs come with side effects, and so we do have to weigh the risks and benefits with patients. But there's a lot of work being done right now to study lower doses of these medications to see. Can we still see the same risk reduction with lower dosages? And there was an early study that came out recently looking at three years of low dose tamoxifen. 5 mg. We really did not see significant side effects in those in that study, but we did also still see risk reduction. So why should we even consider genetic testing? Well, the age of onset of breast or ovarian cancer in a mutation carrier is significantly different and significantly earlier than when we see the general population getting breast and ovarian cancer. So for B. R. C. A one and B R C. A. Two, we see the breast cancer incidents start to rise in the thirties kind of younger thirties for B R C A one and mid to later thirties for B. R C. A. Two. And for ovarian cancer. We see it start to rise in our late thirties and early forties for Bracha one or B. R. C. A one and in our early to mid forties for B R. C. A. Two. And this is important because, as most of us know, we generally see in the general population breast cancer arise more commonly in our post menopausal women. So we don't always think about asking or looking into this for women in their thirties because number one we're not normally doing mammograms for those women if they have no risk or they're not at high risk. And we those women are usually fairly healthy and may not be seeing their primary care doctors or their o b g y n every single year for an annual breast exam for an annual well woman visit. So we really need to be identifying who is at high risk, who may consider genetic testing, who may have a Bracha gene where we really do need to be seeing them much earlier, and those with the deleterious mutation, you know, they may benefit from prophylactic or risk reducing surgery, and it's really important to start the conversation about this with patients early. Um, this is not the right answer for every single patient, and it is a very individualized discussion, and it's not something that you have to do, but it is something that's an option, and it's something to address with patients. There are many patients who are very motivated to undergo risk reducing surgery, and we really need to address all of the things that come along with genetic testing such as psychosocial issues, um, and quality of life aspects. And then we also need to talk to patients about if you do have a genetic mutation and you choose not to have, or we don't recommend a risk reducing surgery, we need to be following you from a high risk standpoint and talk about risk reduction. So who should we even be doing genetic testing on? You know, initially, we only did genetic testing on people who personally had breast cancer, and that is still a fantastic time to offer genetic testing because then we can use that as if someone is positive, cascade down and test their family members who are unaffected but who really qualifies. And this is the current N. C. C N guidelines, which is what we follow for genetic testing. So anyone diagnosed with breast cancer younger than 45 or anyone diagnosed between 45 50 and either they are adopted and they don't know their family history or they have had a second personal breast cancer at any age. So maybe they were diagnosed at 47 but then, at 55 they got a second contra lateral or or multilateral, but different breast cancer. Or maybe they also have one or more family members with breast, pancreatic, prostate or ovarian cancer, which is the cancers that can go together in the breast and ovarian cancer syndrome. We also know that if were diagnosed with triple negative breast cancer, that that poses a higher risk of having a B R C a mutation. So those women, even if they are up to 60 years old, we generally recommend testing. We also look at again the Ashkenazi Jewish ancestry or heritage. And so we do ask women, Are you from Ashkenazi Jewish heritage? Because that it doesn't matter what age you are. You would qualify for genetic testing or one or more family members with breast cancer less than less than 50 or the these mentioned cancers or if they have three or more family members with breast cancer at any age. So maybe the woman presents at 65 but three sisters and aunt and and one grandmother all also had breast cancer. Will that that family would qualify for genetic testing if someone has a personal history of epithelial, ovarian cancer, execution, pancreatic cancer or prostate cancer that is metastatic in an Ashkenazi Jewish male or one or more family members with young breast cancer or ovarian, pancreatic or metastatic prostate or two or more with breast or paint or prostate cancer at any age also qualify. So this is that that person who comes and has ovarian cancer has no family history of anything. She still qualifies for genetic testing and then patients with a family member who has a known genetic mutation. So someone comes in and says, you know, my cousin, who's 35 just got diagnosed with breast cancer, and she was found to have a B R C, a mutation or genetic mutation you can test. You should be testing the family members so that we can find out who else in the family might have this and maybe sitting at high risk. Now we In the past, we used to only test for P R. C. A one and two. Those are the most common genes that we find. Um, but we do know that genetics changes all the time, and we're finding more and more genes that can put us at high risk. And so if we meet the current criteria and the patient has only had Bracha one and two testing in the past, they may actually be able to have updated panel testing qualify. For now. This has been interesting. About two years ago, the American Society of Breast Surgeons came out with a consensus statement that they said that genetic testing should be made available to all patients with a personal history of breast cancer. And this really came because they did a bunch of studies looking at, you know, doing testing only by our guidelines compared to doing testing of all and what did they find? And certainly they found genetic mutations in patients that didn't meet our current N. C. C N guidelines. Maybe this is where we are headed, and I personally think that it is important to know this information, so that might be something that we end up doing in the future. I think at this point insurance has not caught up to this, although I will say that a lot of patients now have access to genetic testing at a much, much lower cost. And if there is someone that is interested in doing testing and they don't meet the criteria, we can still figure out how to get them tested for a very low cost. At this point, I wouldn't say we have all jumped on board with testing every single patient, but we do talk to it, talk to every patient about this as an option. So then you have your patients who have never had cancer before, but they have a family history, and who of those patients should be tested well. The first thing I would say is that if their family member that had the cancer is alive, that person should be tested first, and if that person is found to have a genetic mutation, then the family members should be tested, but sometimes that's hard. Either they're multiple family members, and not everyone can be tested or the family member has died or is unable to be tested. And so there are many people who have never had cancer but do qualify for genetic testing. So you know if they have a first or second degree relative who meets those prior criteria for testing or if the family member had pancreatic or prostate cancer. Um, it has to be a first degree relative if it's just the pancreatic or prostate cancer, but first or second for breast and ovarian. Or if you do the risk assessment tools and someone has a greater than 5% risk of having a genetic mutation like on that tire acoustic, they would qualify for having genetic testing. You can consider it if you have these following. So somebody who's never had cancer but has multiple primary breast cancers in one family diagnosed before 65 family history of Ashkenazi Jewish heritage, or someone who is in that 2.5 to 5% probability of a genetic mutation on the risk assessment tool. And so how do you even go about doing this? Well, there's lots of different ways. I would say, You know, thankfully, we live in a metropolitan area where we have access to genetic counselors and, you know, good or bad because of covid. Now everything is available to be done over zoom, so virtually you can meet with a certified genetic counselor, which used to be a really hard thing to get into for some patients, depending on where they lived. So certainly, certified genetic counselor is probably the most accurate and best way to go. They do have over the phone certified genetic counselors. And because breast surgeons are doing this all of the time and are working hand in hand with our certified genetic counselors, sometimes we can get the process started just in our office at the time of a console. Many general practitioners are also really interested in staying on top of genetic testing and can also be the person that facilitates this Orochi doyennes, and sometimes insurance dictates. What are your options? So what are your options for testing patients? I have mentioned previously that you know, certainly you can consider B R. C. A one and two testing alone. I would say that has really gone out of practice, but that is always still an option. More commonly, we are doing panel testing, and this is often done due to cost effectiveness compared to kind of what we call reflex testing. Which means if you do just the Bracco one and two and their negative and then you go, maybe I should have tested the other ones. Maybe I want to test the other ones you reflex and asked them to run a panel so they're essentially having to do it twice. Um, now, good or bad, Extensive panels can include a lot of genes that are not well studied and we don't know a lot about. However, the more we learn about them, the more will know. Now we can do site specific testing. So if we know there's a specific mutation in a family, we may test for only that mutation if there's no other concerning family history. And then there are some labs that have a specific Ashkenazi Jewish panel, which is kind of called a founder mutation. There's three specific mutations that are most commonly found in Ashkenazi Jewish heritage. So what happens if you do genetic testing. What are your results gonna show? Well, it's not super straightforward for a lot of patients, so we obviously can get a positive result where we say this is a pathogenic variant of pathogenic mutation, and we know that this causes cancer. We can get a negative result where we know it doesn't cause anything, and nothing that we've been able to identify can pinpoint your risk. Or we can get very commonly this thing called a variant of unknown significance. So, um, I think that's gonna I'm going to go into that in a second. But basically, just this is how I explained variants of unknown significance to patients. If you think of each gene like a single line, if you have something on the right, that's abnormal, and we know that that abnormality causes cancer. That's a positive mutation. But on a variant of unknown significance, that abnormality is not there. It's normal, but somewhere else on the jeans something's a little abnormal, and we've never been able to pinpoint. Does that abnormality on that gene cause cancer? Now, as we know, we learn more and more about this. If the labs that do these tests continue to start seeing the same variant over and over and over and people with the same types of cancers. That's how these can get reclassified. And there are times where a variant comes back a couple of years later. And they say, You know, this has been reclassified to a pathogenic variant, or this has been reclassified benign. We treat variants of unknown significance as benign findings, meaning we don't use those for surgical decision making or risk reduction surgery recommendations. So why is it important to do pre and post test counselling? Well testing and affected family members the most informative. So we usually go for the person who is the youngest age of onset or someone who really meets a lot of the criteria bilateral disease, multiple primary cancers. But when we consider testing an unaffected family member, you know it's very important to understand that there's a lot of limitations to interpreting test results. So if there's no mutation found, you may have other hereditary cancer syndromes, Um, and if no mutation is found, you could also have some sort of familial mutation that we have yet to identify. So we still if we test someone in their negative, but they have lots of family history. We still follow them from a high risk standpoint, because we really don't know if we're going to know something later about their genes that we don't know about today. The only time that we might tell someone we know now or we can say with confidence that you are at average risk as opposed to your family member is when Let's say, Mom had breast cancer at 35 she got genetic testing and she has a B R C, a one mutation and then patient. Who is that? You know, the daughter gets testing and she did not get the gene mutation. Now we know that Mom's cancer was due to her Jean, and the patient is not at that same risk. That is not necessarily a patient that we need to follow from high risk as long as Dad's family history is not suggestive. So what are the limitations? Well, if it's positive, it may be on a gene where there's no evidence based recommendations, and that can be really a tough conversation for patients because, hey, we're giving you this information. You have a gene mutation, but we don't really know what that can cause, and that can cause a lot of anxiety for patients. Um, and we may not have for a lot of these genes. We may say we don't really have recommendations for risk reducing surgery, but we do have recommendations for screening, which is helpful. But there are some where we don't even have recommendations for screening, and that can be really difficult for patients. And then also, these results indicate a probability. This is not a certainty. This is not telling someone. You are definitely getting cancer. It gives them a percentage range. With this gene, you have a 60 to 70% or 40 to 50% risk of getting breast cancer. So these are very long, individualized conversations with patients to really understand not only where they sit, but also where they're comfortable with with risk. What's the limitation of a negative test? Well, a negative result is only fully informative. If the mutation has been identified in the family, as I previously mentioned, not all mutations are detectable or have even been identified, and a negative result in an unaffected family member is really helpful for that specific patient and their Children, but it is uninformative for other family members. So, you know, we know if Grandma had breast cancer at a young age or ovarian cancer, then she had six grandchildren, and we've only tested one of them in that family member is negative. The other five family members also should be tested because these genes are passed down about 50% of the time. So there could be a couple family members that do have a gene mutation, and this patient that we tested just is not. And then, as I mentioned, you know, there is an uncertainty with the variants of unknown significance, so some of these will be reclassified in the future. It is pretty rare that something gets reclassified as a pathogenic variant, meaning something that actually causes cancer that is actionable. And so it's. But it can be unsettling for patients to know that this gene is not normal, but we don't exactly know what that means. And so what happens if a patient gets a test result back that shows A B R C a one or B R. C. A two mutation? Well, the risk, you know, increases as we age, regardless of if they have a genetic mutation and their risk of breast cancer is about a 60% or greater absolute risk. And it is a bit different between Braca one and BRCA two, but we usually say about greater than 60% absolute risk. And so these are patients that really do need to be referred to a breast surgeon or a high risk clinic to be talking about. What are your options? Certainly we talk to these patients about Are they interested in risk reducing surgery with bilateral mastectomy with or without reconstruction? And that, for some women, is the answer? And for some women is not the answer. This if we do risk reducing surgery, will reduce their risk of getting breast cancer by about 90 or almost 95%. But it doesn't make it zero nothing that we can do. We'll give them a 0% risk. But if a patient is not ready for risk reducing surgery or is not feeling like that's the right option, then we go back to those screening recommendations that we talked about before for the average or for the high risk woman on the ovarian cancer front. We have about a 39 to 58% absolute risk for Bracha one and up to 30% for Bracha, too. And we generally recommend risk reducing ovarian and fallopian tube removal after childbearing and between 35 to 40 for a break of one and 40 to 45 for a bracket to and really, that's because, as I mentioned previously, this is when we start to see that risk increase. By removing the tubes and ovaries, we reduce the risk for breast cancer by about 50% and we're going to reduce your risk of ovarian cancer by at least 80% now, if that's not the right option for that patient or they're not ready for that. We do recommend oral contraceptives for risk reduction. And the difficult thing with ovarian cancer, as we probably all know, is that while we have great screening tools for breast cancer, we do not have great screening tools for ovarian cancer. So while we can do trans vaginal ultrasounds and see a 1 25 levels and lots of different screening modalities, we are not fantastic about picking things up when they are early stage curable and treatable pancreatic cancer has a lot of emerging emerging data for screening, and currently we reserve those for patients who not only have a mutation but also have a family history of pancreatic cancer. So not every single patient with a B R C. A one and two mutation needs screening at this current state for pancreatic cancer. But if they have family history of pancreatic cancer, we may recommend a contrast MRI or RCP, or an endoscopic ultrasound. And the interesting thing is that studies that are coming out have shown that screening can detect pancreatic cancer at an earlier stage at about where it becomes about 75 to 90% of the time. Respectable. Which, as we all know, a lot of pancreatic cancer is un respectable by the time we identify it. And then when it comes to males with BRC one, we do recommend this breast self exam and an annual clinical breast exam because they are at risk of getting breast cancer. You certainly can consider an annual mammogram, especially if the patient has gynecomastia starting at 50 or 10 years before the youngest family member who was male with breast cancer or you can just stick to the clinical breast examination. There isn't a great guideline around. Do all of these patients need a mammogram? And we do recommend prostate cancer screening starting at 40 for B R C. A two, and we consider it for BRC one. Now we're about to look at the other genes that increase our risk in our current and CCN evidence gives us very strong, strong or limited evidence, depending on the studies that have been out there for each gene. And it will also give us our absolute lifetime risk in ranges and compared to the population risk. So if you kind of just think about that as we look at this next slide, that's very busy. These are the next set of genes that increase our risk of breast cancer. I did put grip one in here that we really don't have great data for breast cancer on, but we do have great data for ovarian cancer. And so really, what this shows is what is our risk of breast cancer with all of these genes? What is our risk of ovarian cancer? What are the other cancers that we may be at risk for. And as you'll see here, there's actually only a couple of genes that we have strong data to say that we should recommend risk reducing mastectomy or risk reducing scalping. Goof rectum e So for breast cancer. In addition to the B r C. A one and two gene, it's relatively limited to PAL B two, P 10 and TP 53. Now this is we're talking about risk reducing mastectomy, meaning for a woman who has never had breast cancer. If a woman who has breast cancer is found to have one of these genes, we don't have a lot of great data on a lot of these genes about what is their risk of a subsequent breast cancer. A second Contra lateral or second? It's a lateral, but in a different quadrant breast cancer, not a recurrence of their current breast cancer. So it it becomes a long discussion with patients about who really wants to go down the road of bigger surgery that may or may not improve their survival and outcome, as opposed to patients like Barack, a one and two where we know doing bigger surgery gives them a better outcome. Now, what can we do about this? So now we just told this patient there at significantly high risk, and now they're all anxious about what can I do about this? So there's a lot of things that you can do for risk reduction that don't necessarily include medications. So we have a lot of non modifiable things that there's nothing you're going to change about, how old you are, the gender you were born with, the race that you are, whether you've had a tibia, radiation or what time you started your period or or stop your period. There's a lot of modifiable risk factors that we can make changes today that can help us decrease our risk, and we're going to go through those in just a minute. So interestingly, a lot of data is coming out about diet and exercise. And really, what we're finding is, not surprisingly, a diet rich in vegetables. Fruits. If people are meat eaters, poultry and fish instead of the red meats will is linked to lower risk of breast cancer. Studies have shown that doing about a 30 minute brisk walk five days a week can reduce our breast cancer risk by 18 to 30% and we see more reduction of risk with more intense workouts. So the more we can do strength training, and we can combine this with eating a healthful diet. I generally tell patients, as long as you make good decisions 80% of the time with your diet, you are doing the right thing. If we see a B M I greater than or equal to 28 in postmenopausal women, that has shown to increase our risk by 26% so we can keep our BME down. That shows significantly decreased risk. Alcohol intake is something that has also shown an increased risk of breast cancer. And if we think about greater than or equal to 30 g per day, or the equivalent of about two glasses of wine, that can increase our risk by 30 to 40%. So either abstaining or decreasing our alcohol intake. So usually tell patients one drink per day is recommended by the American Cancer Society as the maximum that can help decrease your risk. Unfortunately, night shift work has also been associated with an increased risk of breast cancer, and we see an increasing risk with increasing numbers of years or hours worked on night shift, and this is really thought to be associated with melatonin is tumor suppressor suppressive qualities. And this is a hard one, because, uh, it may not be that easy for someone to just change the shift that they work. We are also learning a lot about environmental exposures. So parabens, phthalates, triclosan, um, these are considered endocrine disruptors, and you know, women use a lot of personal care products per day. At least 12 is usually the average. And so this is just an example of a study that was done a couple of years ago at U C. Berkeley with the California Department of Public Health. And they took 100 Latino teens in Selena's, and they asked them to use low chemical personal care products for three days alone instead of their regular products. And then they checked their urine, phthalates, parabens and tripe, listens, um, pre and post intervention. And in just three days of changes, they saw urinary concentrations decrease by 28 to 44%. So this doesn't tell us what that means, and there's a lot of ongoing studies about this, but this is just an example that everything we put on our body comes into our body. And here's some good websites that I share with patients or apps that are, if patients are really motivated to try thinking about cleaner products or cleaner. Um, you know, skincare products like lotions. Whatever they're using, there are ways to learn about how to find products that may have less of these environmental exposures in them. I certainly don't tell patients clean out your medicine cabinet, but there are patients that just want to know what can I do? And those are my references from today, Um, this is all of the contact information. So at the U. C s F cancer care at our Berkeley outpatient center, myself and Dr Abe are the two surgeons for Breast. And then Dr Malhotra is a medical oncologist, and Dr Marshall is the medical oncologist that specializes in breast cancer, and she's also a medical director, And I put on here our email addresses in our cell phone numbers and this please feel free to reach out to us at any time with any question. No question is silly, or if you have a patient that you just need to run by us or you'd like us to see. We're happy to help expedite that process. And that is all. This is how this is our phone number and fax number of how you can refer patients to the Berkeley Outpatient Center.