John Plemmons, MD, and Rachel Burke, MD, give their updates on breast cancer screening and patient management, with a focus on the high risk population.
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Return to Main Symposium Page I want to introduce myself. My name is John Plemons on the medical director of the Breast Center at Norfolk General Hospital and Norfolk, Virginia. Dr. Burke and I wanted to speak today on the topic of the screening and management of women who are at high risk for breast cancer is the topic that's become, um, I think, an area of of increased interest as we look to, uh, try to develop a more tailored approach to screening so that women who are perhaps do not benefit from annual screening can be identified in the appropriate, uh, surveillance recommendations can be made. And yet at the same time, we don't want to lose those women who in fact, may benefit from enhanced screening and our ability to do genetic testing. And thio understand some of the molecular basis for some of the A tip. Ia's and the breast cancers that the pathologists are giving us are helping us to make some of those recommendations. So it is an interesting time to be involved with breast cancer detection on treatment. So I am. This article comes uh, generally from the American College of Radiology, was based on an article published published in the Journal of the A. C. R. Back in March of 2018. There haven't been any substantive changes to how this is, uh, the guidelines that we that I'm going to share with you today. I will apologize in advance. Radiology articles tend to be very picture intense. That's what radiologist like nice, pretty pictures. But unfortunately, this topic doesn't really lend itself as well to that. We do have some objectives today. We're going thio touch. Based on the current literature regarding the benefits of early breast cancer detection, we're going to identify what patients should be considered high risk for breast cancer and who may warrant genetic counseling and or testing. And we want to be able to identify what imaging modalities are best suited for the detection of breast cancer, particularly among women at high high lifetime risk. Have no disclosures. We know that early detection decreases mortality for women with breast cancer. The A C are currently recommends annual demographic screening beginning at age 40 for women at average risk for breast cancer. On the basis of an extensive literature review. I'm aware that many of the guidelines many of the task Force and other agencies have modified some of their recommendations. Um, this can be debated. The American College of Radiology has not modified its recommendations, and so those are the ones we're discussing here in this article. Women with additional risk factors placing them at higher than average risk for developing breast cancer need further consideration for earlier and dorm or intensive screening. These women typically have at an age less than 40 a risk equivalent to or higher than that of an average risk woman at the age of 40. Breast imaging experts Experts from the A. C R Commission on Breast imaging have reviewed AH wide body of literature and used robust strength of evidence mythology to sort of developed these guidelines. Okay, Our recommendations for women in the higher risk population are based on the latest data available regarding the use of Marie ultrasound, molecular breast imaging, digital breast, homo synthesis and addition to digital mammography. Um, we know that there are several risk factors that can increase the woman's lifetime risk of getting breast cancer. Certainly, genetic predisposition is one of those risk factors, and yet we see that only in about 5 to 10% of women who have a breast cancer. The lifetime risk for breast cancer. For women with BRCA one and BRCA two mutations is certainly elevated. For Bracha one, it's approximately 50 to 85% and for bracket to its approximately 45%. Women of Ashkenazi Jewish descent are known to be at high risk for both brackey mutations, as well as higher rates for other actionable mutations. We've come a long way now in identifying genetic risk factors for not just breast cancer in addition to Bracha one and bracket, too, but other types of cancer TP 53 check to the P 10 gene mutation CDH one STK 11 Poppy do an a T M. R. Some of those examples, and one of the challenges that those of us who deal with identifying breast cancer and high risk women and certainly for those who manage those patients, is that when you get some of these genetic mutations, you identify those genetic mutations. They're not just elevated for breast cancer. They have a higher risk for ovarian cancer for pancreatic cancer for colon cancer, sometimes melanoma, other malignancies. And so the breast surgeon, um, needs to partner with his or her clinical colleagues to identify other Agilent screening methods. Uh, you know, do we need to do increase? Colonoscopy is body emery or ultrasound something that would add value. So this is the area that's sort of the new frontier as we begin to identify some of these genetic mutations women with strong family histories or higher, higher risk even in the absence of known genetic mutations, we know that there certainly known genetic mutations that are unknown but are almost certainly exist. The number of family members with breast cancer, especially first degree relatives and their age of diagnosis, are important considerations. Women who have had Hodgkin's lymphoma and who have been treated with chest or mantle radiation therapy are certainly at high risk for breast cancer. And we advocate in the A. C R recommends screening eight years after the completion of radiation therapy. Um, this is similar to Bracha one and two carriers, whose cumulative risk by age 40 is 15 to 18%. This is S O that these Hodgkin's lymphoma patients who have had mantle beam radiation find themselves in a category very similar to Bracha one or bracket two carriers. Remember that the other number that I had given you. The higher risk, which is close to 60 to 70 to 80% for bracket, too, is really based on a lifetime risk. Now we're talking about cumulative risk before the age of 40. We know that women with personal histories of breast cancer or at risk for recurrence or a second breast cancer um, we also know that the risk for contra lateral malignancy in these women's with these women is about half the 1% per year during 10 years after the diagnosis. Um, we know that a lot of these women, of course, when they're under the care of a breast surgeon, will get hormone therapy and to chemotherapy, which lowers this risk. But women diagnosed with early estrogen receptor positive cancers remain at increased risk for future cancer about 10 to 20% respectively, for five and 10 year follow up Risk analysis shows that all women diagnosed at or before age 50 and treated with breast conserving therapy have a 20% or higher lifetime risk for new breast cancer. Women with lobular neo pleasure in l H L. C s. These women have ah lifetime risk of between 10 and 20% for women with the diagnosis of LCS lobular carcinoma. Insight to that increased risk is bilateral. It really reflects ah, systemic risk for breast cancer. And most of these cancers air gonna occur within 15 more than 15 years after the diagnosis. A th, which we certainly see frequently and which we typically treat surgically, also confers an increased risk, but to a lesser degree than L C s at a median follow up of 17 years, the relative risk for invasive cancer is four to fivefold for women with a TH and 6 to 10 fold for women with LCS. Recent work shows the cumulative risk for invasive cancer 10 years after a diagnosis of a D. H was 2.6 times higher than that without a d. H. We know that white and black women have the highest incidence rates of breast cancer of any group, and their currents rates are now similar. However, this is an area of concern both for a CR society of breast surgeons. A meta analysis found that black women were 19% more likely to die of their disease. Recent data from the American cancer society shows that non Hispanic black women have death rate 39% higher than non Hispanic whites, and we're concerned that reasons may include access to mammography as well as health care, delivery patterns and tumor biology. For certainly in these young black women, we see it is well recognized. A, uh a um increased risk of triple negative breast cancers. Black women experienced delays in diagnosis and treatment and radiation, which negatively affect survival. Although stage of diagnosis, tumor characteristics and body mass index are all contribute to racial differences in survival, disparities exist even after adjusting for those factors. This is what I was alluding to earlier. Recent data shows a twofold higher population based incidence rate of triple negative breast cancers in women compared to white American women in all age categories. We see this clinically over and over again. It's a pattern that is very quickly recognized when you practice breast imaging. Um, use of next generation sequencing found that 65 of 289 black women with breast cancer had inherited mutations. This might explain the increased risk for young onset aggressive breast cancers and black women. There is an increased risk for developing breast cancer among women with dense press usually defined as heaving, either having heterogeneous dance or extremely dense breast tissue. This, of course, is ah, effective state Legislature. We know now that Virginia requires us and has required us for some time. Thio Disclose Breast Density This began initially in Connecticut as part of an effort, Thio allow women to have more insight and knowledge about their breast health and about their risk for developing breast cancer. The A. C R was initially concerned about sharing that information because, quite frankly, it was not clear what recommendations we would make for women in that category. We've moved beyond that at this point. I think we can handle Way can provide some guidance and insight for women who are find themselves in that category. Um, I would just highlight on the screen that about 43 to 50% around 45% of women older than the age of 40 will find themselves in that category of dense breast tissue. So it's certainly not a rare phenomenon, and when we talk about relative risk for dense breast tissue, it's important that we understand exactly exactly why what it is we're referring to, For example, the relative risk for a woman who has extremely dense breast tissue maybe four times higher than women with predominantly fatty breast tissue, but sets most women don't have extremely dense or fatty. We're really talking about differences, sort of in the middle. And so what? We wanna recognizes that most women are gonna have either scattered fiber, glandular densities or heterogeneous. Those are the two of the four categories that sit in the middle. And when you compare those two between scattered and heterogeneous, the relative risk factor for breast cancer is only about 1.45 So it in and of itself, it doesn't warrant additional regiment screening methods. And this is something that you and the clinical practice will find yourself dealing with because women will say, We want rest Marie. We want ultrasound for those women and then, in a case by case basis. That may be appropriate. But as a general carte blanche recommendation, it's not something the A C R advocates. We certainly developed many Rodel models for risk assessment, and you guys will see often in reports the tire, acoustic model and risk factors. The problem with the tire acoustic model is that unless there's good information in the information on the other side is often not reliable, and patients often don't understand to the level that the tire acoustic demands what they're the personal and family history is. We often see on the clinical input sheet the patient completes when they come into the breast center one year, they may say that their their sister had breast cancer and, excuse me, ovarian cancer. And then the next year she has a cervical cancer. And then when you ask her, she says, Well, it's one of those female cancers So there's these things matter in terms of calculating the risk. But the understanding, um that's necessary to get this form isn't often present in our in many patients. So what we try to do is identify patients who may benefit from sort of a clinically directed assessment through you through genetic counselors through high risk specialist, to really try to get at the information so we can come up with a meaningful number we use the tire acoustic model has discussed. I'll skip through some of these, uh, to determine breast cancer breast emery eligibility the American Cancer Society recommends models that incorporate 1st and 2nd degree family history such as the Clouds, the Tire, Kosek, Bracha, Pro Onda, other algorithms. But you'll find tire Acoustic is probably the one that has been tested and perhaps has become sort of the industry standard. And I will point out, however, that despite good calibration is this thing. Models discriminate an individual's risk with only moderate accuracy. So if you tell a patient you know she's got a 25% lifetime risk for breast cancer based on the information in the tire acoustic model, um, you know, you really only can take that So far. I want to say that breast density tends to be higher, tends to be higher out women at younger ages, of course. Um, and for some women who have a higher risk, those with genetic predisposition or strong family history, this is often coupled with biologically more aggressive tumors. And the concern, of course, is that sensitivity for breast cancer in standard digital mammography is only 25 to 59% and higher risk women. So we're kind of in a situation where women mammography is not as effective in women who might ultimately be at a higher risk not only for developing breast cancer but for developing breast cancers. That arm or biologically aggressive? Let's took it. Talk about what imaging modalities air out there and some of them. Of course, I don't think any of this is gonna be news to anybody completely. We know that the digital mammography improves cancer detection and dense breast tissue compared with previous film screen techniques. This is, I would say, something that I don't see emphasized enough in my literature review in my clinical practice when we moved moved from film screen to digital Theobald iti to see through dense breast tissue. Um was night and day and we suddenly started finding things that we never could have seen before. Um, the largest performance improvements occurring women less than 50 years of age and those with higher breast density. Because younger women generally have done sir breast higher risk. Women with who began screening at an earlier age would also be expected to benefit from digital breast Thomas synthesis. We know that digital breast homo synthesis. Now this is sometimes referred to his three d mammography. Um, will detect more cancers and also decrease the false positive recalls. So decrease the rate of call backs that ultimately are not necessary. Three effects of digital mammography and digital breast home. A synthesis and higher risk women are similar to those described in average risk women. Because higher risk women frequently begin screening at an earlier age, Each woman may undergo a greater number of screening exams and therefore may experience an increased number of false positive recalls and biopsies. Although bracket mutation carriers may be particularly susceptible, radiation the low radiation does from screening mammography does not demonstrably increased their breast cancer risk. I will make the one distinction. There is a distinction between our break of one and a bracket to patients. The benefit from beginning screening mammography early at the age of 30. For Bracha one was not clearly demonstrated, but for bracket to waas. This is in addition to undergoing adjuvant breast temarii. By the age of 40 to 45 years, 13 to 20% of women treated as Children or adolescents with mental radiation therapy will develop breast cancer. This population should begin screening at age 25 or eight years after the completion of therapy, whichever is later breast. Tamar I we know. Contrast. Enhanced Press Tomorrow is known to increase cancer detection and the higher risk women and is more sensitive than either mammography or ultrasound in the high risk populations. In a recent study of brackey mutation carriers and women of 20% or higher lifetime risk for breast cancer, the sensitivity for breast cancer detection was 90% vs 37 a half percent for mammography and 37 a half percent for ultrasound. Similarly, patients who are Bracha one and bracket to mutation carriers Marie Sensitivity was 68% compared with 37% from mammography and 32% for ultrasound. Marie has consistently been shown to outperform mammography and ultrasound even when both mammography and ultrasound are used together. Recommendations have been established supporting the use of memory and women with genetic based increased risk. And they're untested first degree relatives, women who received chest radiation therapy before the age of 30 and women with a calculated risk of 20% or more data continue to accumulate to support these recommendations as well as some refinements to them. In previous recommendations, less certainty was expressed for the use of Marie and women of intermediate risk those with personal histories of breast cancer with LCS or a Tippee it biopsy with a calculated risk of 15 to 20% or with dense breast tissue. We're continuing to study these areas so that we can begin to clarify the use of Emory in some of these groups for bracket gene mutation carriers. Emery was initially recommended as a supplemental screening modality, starting at age 25 to be obtained. In addition to annual mammography at and beyond age 30 that recommendation remains solid. Since our previous recommendations, however, there are additional outcome data confirming the high cancer detection rate using Emory in this population from, however, recent studies suggest that mammography only adds a small, small amount of increased cancer detection in Bracha one carriers under the age of 40. That's a relatively small subgroup of patients on, but and it is something some of the breast cancer breast surgeons are aware of. Um, ultimately Mawr evidence is needed to assess the role of mammography and Bracco one carriers bracket. Two carriers, however, benefit more from mammography. In addition to Emory, about a third of cancers and these women were found on Leon Mammography. How is that possible? We know that Marie often doesn't detect DCs. The calcifications that can be associated with even high grade DCs can sometimes on Lee, be seen on mammography. And the enhancement that Marie is looking for often can be subtle and obscured in women who have quite a bit of background. Perrin Camel enhancement Patients with histories of chest or mantle radiation therapy under the age of 30 benefit from memory. I want to talk about women with a personal history of breast cancer because, quite frankly, that's what we see the most right, not our break of one or two patients or other genetic mutations. Or are Hodgkin's lymphoma patients who have had mantle radiation? What we see are patients who have a personal history of breast cancer and who also have have no known genetic mutation and who may have dense breast tissue. Um, so we found sensitivity for breast cancer and those women at 85% versus 23% from mammography. Early wet work in patients whose sole risk factor is a personal history showed that the cancer detection rate with Marie was high. 10.6 although isolating personal history is the sole risk factor was difficult and resulted in small study numbers. New studies reaffirmed these results. Consistently. Higher cancer detection rates with M R I. 10 to 29 cancers per 1000 women with a personal history of breast cancer. All right, I want to get into our ultrasound discussion before we run out of time. Breast ultrasound has is confirmed. Thio pick up additional breast cancers. But the problem with breast ultrasound is that it has a very low, uh, positive predictive value. You will pick up in additional 3.2 breast cancers per 1000 women with breast women who, um, who undergo breast ultrasound. But the number of unnecessary biopsies and unnecessary surveillance has been found generally to be unacceptable, and that sort of reflected and reduced enthusiasm for this modality. Um, the Akron 6666 A Large Perspective Multi center study Evaluating women at elevated risk, most having dense breast in combination with other risk factors, found a supplemental cancer detection rate of 4.3 per 1000. The cancer is found by ultrasound tended to be invasive. They tended to be small 10 millimeters average size and the patient was no negative. However, it is associated with an increased risk and false positive findings and a lower positive predictive value. Short term follow up was also recommended at an undesirably. High rate is up to about 9% versus 2% from mammography. Basically, we're ultrasound is causing ah lot of unnecessary biopsies, and on a lot of follow up that may not be clinically warranted. So until the specificity gets better, three use of whole breast ultrasound particularly that's that's handheld directed by either a stenographer or a breast radiologist is generally not recommended. We do make exceptions to that. We've had patients who cannot tolerate mammograms absolutely cannot tolerate them. We explain the benefits, but they just will not undergo it. And rather than lose those women to screening, we will sometimes do breast ultrasound, and we'll do it on a case by case basis otherwise as well. All right, want to get into just quickly touch on molecular breast imaging. Molecular based imaging of the breast involves an ivy injection of a radio pharmaceutical agent, and subsequent imaging uses a dedicated breast specific camera, preferably dual headed to detect abnormal accumulation of radio activity that could signal the presence of breast cancer. It does show very good sensitivity, and it also shows good specificity, although perhaps not as good for tiny cancers because of less resolution. And for ductal carcinoma Insitu, which is sort of one of the other limitations of Emory. Um, it's not hampered by breast density, as opposed to say, for example, mammography. I will tell you that we participated in, and we published an article in the great journal that discussed the use of molecular based imaging for its surveillance of neo adjuvant response to chemotherapy. And it really is probably better than Marie. But now we're focusing purely on as a screening modality. And one of the problems with molecular braced imaging for for a screening tool is radiation radiation exposure. So recent studies in which breast density was exclusively or mainly the conferring risk factor showed a molecular based imaging showed incremental detection rates of 8 to 9 per 1000. That's pretty significant. With a median tumor size of about a centimeter. That seems to be the lower cut off from molecular breast imaging. With the current detectors, which are currently improving considerably, The problem is the radiation exposure for these women because it's injected and it is systemic radiation. It's about eight million curies s so far in advance of what we could see for mammography. And the benefit risk ratio is not acceptable currently because the bio distribution of radioactive substances results in whole body radiation exposure and result in higher estimated lifetime attributable risk. Dose must be carefully considered when evaluating molecular breast imaging for screening and analysis. Comparing the benefits to radiation risk ratio of mammography versus an eight military MBA exam showed a higher benefit ratio with mammography for all 10 year age intervals examined. So mammography better, better a risk benefit ratio, the molecular breast imaging for all ages studied. In order to make that equal, we would need to be able to cut the risk. The radiation exposure for molecular based imaging significantly, probably in magnitude of 50%. We are working on new detectors, so let's summarize this. All women, especially black women and those of Ashkenazi Jewish descent, should be evaluated for breast cancer risk no later than the age of 30 so that those at higher risk can be identified and can benefit from supplemental screening for women with genetic based increased risk, and they're untested first degree relative or with a calculated lifetime risk of 20% or more. Digital mammography, with or without digital breast home of synthesis should be performed annually beginning at the age of 30. Braca one Carriers may consider delaying the start of mammography screening until age 40. Onley if they're imaged yearly, with contrast, enhanced breast temarii starting at age 25 for women with histories of mantle or chest radiation therapy who received a cumulative dose of 10 gray or more before the age of 30. Digital mammography, with or without digital breast home with synthesis should be performed annually beginning at age 25 or eight years after radiation therapy, whichever is later for women diagnosed with breast cancer 88 or lobular nia pleasure. Before the age of 40. Annual screening should begin at the time of diagnosis for women with genetic based increased risk. And they're untested first degree relatives, history of chest radiation or with a calculated lifetime risk of 20% or more Breast. Emery should be performed annually, beginning at age 25 to 30 for women with personal histories of breast cancer and dense breast tissue or those diagnosed before age 50. Annual surveillance with breast Tamara is recommended for women with personal histories of breast cancer not included in the above or with LCS or a Tippee A on prior biopsy. Emery should be considered, especially if other risk factors are present for women with elevated risk who would qualify for but cannot undergo? Breast Marie Agilent screening with ultrasound should be considered. It has some of the limitations that we've already discussed for women with elevated risk limited to increase breast density, ultrasound can be considered after weighing the benefits and the risks. Molecular breast imaging is not recommended for screening surveillance in any high risk population currently. All right, at this point, I want to end my part of the presentation. I'm going to turn over the discussion of the management of these patients to my good friend and colleague, Dr Rachel Burke. And I thank you for your attention. Hi, My name is Rachel Burke. I'm a surgical oncologist. A. T. V. M s first cancer accounts for a significant portion of my practice. I appreciate the opportunity to participate in this conference since I know It is primarily an image in conference. But Dr Plemons and I thought it would be useful to include information on what to do with patients who are at high risk for breast cancer beyond just the imaging screening protocols. So management options include enhanced screening, which Doctor Clements has covered in detail. And that may be all that some patients request or desire. Um, many patients, however, have more options, which can help to reduce their risk for breast cancer. I'll discuss genetic counseling and testing lifestyle modifications, hormonal prophylaxis and risk reducing surgery. Genetic testing and counseling takes time. It requires a discussion with patients up front regarding the implications of testing and the significance of both positive and negative results. It also takes time to go through a patient's family history and detail to determine whether or not they're appropriate candidates for testing. Traditionally, this has been done by genetic counselors, but they're in short supply, both locally and nationally. So many surgeons air starting to doom or genetic testing and counseling. It's also becoming a little bit easier because the concept of genetic testing is familiar to most patients these days, so it does make most sense to test an affected family member first, if you can. But when you have a high risk patients sitting in front of you, it's often easier just to move forward with testing that individual. I included the next two slides to emphasize that the criteria for genetic testing is actually quite broad. These are the current guidelines. It takes just one first or second degree relative with breast cancer at a young age or ovarian male, breast cancer or pancreatic cancer at any age to meet their criteria for testing. Unfortunately, only a small percentage of patients who qualify are actually getting tested. And this includes both patients who are primarily affected by cancer and those that were high risk based on family history. Genetic counselors really excel at delving into a patient's extended family history to identify potential cancer syndromes such as leave for how many, which includes sarcoma and breast cancers. Captain's disease, which is associated with breast and thyroid cancer, or hereditary diffuse gastric cancer, which carries a very high risk of lobular breast cancer. So identifying a specific mutation in a patient can help to mitigate risk for these other cancers. In addition to breast cancer through additional screening their number of options for genetic testing when there is a known genetic mutation in a family, patients are generally tested for that specific mutation, which is a more cost effective approach. Otherwise, we typically end up ordering a broad panel. There are many available from various different manufacturers. Um, there are what we call comprehensive panels or smaller ones, such as breast of variant panels that obviously focus on a specific disease process. The myriad My risk panel is one that we frequently order, which covers breast and ovarian cancer. Let's move on to lifestyle management. So if you're in primary care, you're probably better than I am at talking to patients about these kinds of things. We all know that obesity, excess alcohol and smoking are bad for you. But many patients don't recognize the impact that these have on their cancer risk. There was a large study in the UK called the Million Woman Study that showed a nearly 30% higher risk of breast cancer in obese women. And the risk for breast cancer from obesity does differ between pre and post menopausal women across ethnicities and between subtypes of breast cancer. premenopausal women are at higher risk for triple negative breast cancers, but we see a bigger impact in the postmenopausal population with estrogen receptor positive breast cancers right with alcohol. Even light consumption, which is defined, is upto. One drink per day can increase the breast cancer risk by 4 to 15% and each additional drink increases the risk by 7 to 10%. They're epidemiologic studies that show that alcohol use in younger women, adolescents and young adults have more of an impact because that's when the breast tissue is developing. Stop. And, as you probably know, hormone replacement therapy is a known risk factor for breast cancer. The risk varies depending on the combination of estrogen and progestin ins, and estrogen. Onley formulations carry a lower risk. The risk also increases with the duration of use. So as you know, there are pros and cons to hormone replacement therapy. But it's probably not a good choice for a patient who is already known to be a high risk for breast cancer based on family history or personal history of a typical hyperplasia. The factors that reduce the risk of breast cancer include exercise, breast feeding and by lower who for ectomy prior to age 45 a prior use of risk producing hormonal therapy. So, like obesity, the lack of exercise is not only associated with a higher breast cancer risk, but also with poor outcomes and women affected by breast cancer. Data on breastfeeding is variable Um, in one recent meta analysis, women who had ever breast fed were compared to those who had never done so, and the relative risk was demonstrated to be 0.6 in favor of those who had breast fed. And, of course, longer duration of breastfeeding is felt to be more protective. Bilateral bilateral affect me impacts the risk of estrogen positive breast cancers. In a study of about 40,000 women who underwent hysterectomy for benign conditions, three authors compared those who had hysterectomy with bilateral Oof wrecked me versus those who had his direct me alone and those who had the bilateral You for ectomy had a 14% lower risk of breast cancer, and the benefit appears to be greater when performed at a younger age. That being said, um, in this study, the women who had bilateral oof correct me also were noted to have a higher all cause mortality, and this may be due to hormonal effects on cardiovascular disease and stroke, although it's difficult to say for sure. But we know that hormone replacement therapy does affect many different organ systems. Sure, so hormone prophylaxis. Um, this is, uh, something that we would consider in women with a lifetime risk greater than 20% and a life expectancy greater than 10 years. The U. S Preventive Services Task Force recommends that clinicians offer to prescribe risk reducing medications such as tamoxifen. Relax, Safin for Roma tase inhibitors to women who are at increased risk for breast cancer and at low risk for medication effects. And this is a quote from their recommendation statement, which was published in JAMA in 2019. So basically, women who are greater than 20% risk include those with strong family history and those with a typical hyperplasia. A typical hyperplasia increases a woman's lifetime breast cancer risk to at least 30%. Hormone prophylaxis helps to prevent estrogen receptor positive breast cancer similar to you. For ectomy, the typical duration of therapy is five years, with the benefit and risk reduction extending 10 years and beyond women's starting therapy should have normal up to date breast imaging. If they're premenopausal with an intact uterus, they should have a normal baseline. July an exam, and if they're post menopausal, they should have a baseline bone density test. In pre menopausal women, Hormone prophylaxis can be offered starting at age 35 or when the woman is done with childbearing. Typically, it's tamoxifen, 20 mg a day for five years, and this will reduce breast cancer risk by about 49%. The risk reduction is actually far more significant. Women with a typical hyperplasia. It's up to 86% common side effect with tamoxifen or hot flashes. Um, vaginal discharge, sometimes joint pains. There are risks also, of course, which include trombone, bolic events, cataracts and and Demetria cancer. The endometrial cancer risk is estimated to be about 1%. Relax. Iffing is similar to tamoxifen, but studies show that it's a little bit less efficacious, Um, and at this point it's only being used in clinical trials for pre menopausal women in postmenopausal women, the first choice is typically in a row. Mattei's inhibitor, which would be XMS stain and an Astra zawl. They can reduce breast cancer risk by 65 53% respectively. But they're not a good choice in women with osteoporosis or osteopenia. So in those women you might choose tamoxifen or relax of things. Relax. A fine does have, ah, decreased risk of endometrial cancer, So that would be a better choice in a woman with an intact uterus. And finally, I'll just review risk reducing surgery. Bilateral risk reducing, formerly known as prophylactic mastectomy and bilateral risk reducing south Penghu. Correct me are the two choices essentially, and surgery is typically reserved for patients with known genetic mutations. Bilateral risk reducing mastectomy is the most effective way to reduce a woman's risk of breast cancer, and it reduces the risk by at least 90% in some studies. Quote 100%. It also negates the need for screening imaging any scar to any excuse. Many residual breast tissue that's president is typically right under the skin flaps and superficial to any implant so can be detected on physical examination if there are any masses. Typically, those women are still followed with routine physical examinations, but the survival benefit for bilateral mastectomy over enhanced screening is unclear With enhanced screening, We tend to identify cancers at earlier stages and so that pretends of good prognosis. We do know that B R. C A. One patients tend to have triple negative or other more aggressive breast cancers, and so there appears to be more of a benefit to bilateral reducing mastectomy in those women. Bilateral mastectomy not only reduces the risk of cancer, it also reduces a lot of anxiety and fear in women who are at high risk. Every time a woman undergoes a screening examination for breast cancer, they tend to have a spike in their anxiety. And so, um, getting rid of those exams can be pretty significant for women. The downside to bilateral mastectomy obviously that it z an invasive procedure and frequently it requires multiple surgeries to complete the reconstruction, and many women undergo a number of revisions. Surgery can lead to decreased overall body image, decreased sensation decrease in sexual function. But nipple and skin sparing options which we typically recommend for these women these days, committee gate some of those effects. The vast majority of women who opt for risk reducing bilateral mastectomy are happy with their decision in the long term. Okay, finally, bilateral risk producing south Penghu fracked me. So this is typically done N p r c a one and two patients to reduce the risk of ovarian cancer. But as discussed earlier, it can also reduce the risk of breast cancer to some degree and that specifically would be estrogen positive breast cancers. Excuse me, estrogen receptor positive breast cancers. So earlier studies that were done showed up to a 50% reduction in risk in breast cancer with bilateral risk reducing helping goof wrecked me. But there was probably some selection by us in these studies. Um, but we do know that the risk may be better or greater. Um, he's with the risk reduction may be greater NPR, CIA to patients again because the BRCA one patients tend to have more, er, negative tumors. And interestingly, in my own practice, I've seen many premenopausal women who are diagnosed with breast cancer actually opt for bilateral who for ectomy because we frequently treat those women these days with ovarian suppression, which is a shot that they get once a month. And so a lot of those women would rather have bilateral ufer ectomy and undergo the those monthly injections for the ovarian suppression. So that's the end of my presentation. In summary, I would encourage you to identify women who are at high risk for breast cancer at an early age, ideally before age 30 so that we can get them referred to a surgeon who will follow them long term and follow the screening protocols that Dr Plemons has reviewed. Um, also, you should be able to discuss modifiable risk factors with them, um, and and other risk reducing options that are available to them. Thank you. Yeah.