Delivering exciting new data on outcomes for various lesions and therapies, this update from breast surgeon Karen Goodwin, DO, covers everything from how to answer patients’ questions on mammogram frequency to how to counsel them on breast cancer prevention. Included is information on the WISDOM Study, open to any patient who would like more control and personalization of her screening options, as well as a discussion of how surgical decisions have evolved based on node biopsy results and other factors. Bonus: insight on when postsurgical radiation is worthwhile.
So today we're gonna talk about breast cancer advancements and sort of where we've come to where we are today. So the big three things we'll talk about is the updates and screening and diagnosis, up, updates in treatment and then updates in breast cancer prevention. So as I'm sure many of you know, there are currently mammography is still the gold standard of care, screening tests for the breast. But there are a wide variety of recommendations on when to start how frequently to start and various ways to screen women. Um And we're also doing a lot of studies in are there other imaging modalities that should become our standard of care, which is currently um again, currently with mammography. So if you look and I would not expect you to be able to read these slides. But this is just an example of various different organizations that give a wide variety of different recommendations on when to start screening mammography. Some talk about screening at 40, some, talk about screening at 45, some start at 50, some say annual, some say every other year and it's really all over the board, which I can imagine as a primary care doctor can be ridiculously hard to make recommendations for patients. So um I think these slides will be available to you. You can certainly look through this um in, you know, in if you want more detail. But basically what I think I might be missing a slides. Sorry. Um What we're looking at is a mixture of screening modalities with breast, ultrasound, breast M R I with and without contrast, more detailed mag mammography such as three D or toma synthesis and even potentially contrast enhanced mammography, which is just kind of coming down the pike and maybe even something called Mammy Pet, which we'll get into um or can talk about later. But essentially what we're trying to say is, you know, current recommendations are to say we should get a man Either annually or every other year starting somewhere between 40-50 and going until 75 or when a woman has about 10 years left of life and where we should be going and where I think we're headed in the future is how can we find a way to actually individualize screening rather than just saying the whole swath of women in America need to have the exact same screening. And the real question is, is this the future, can we actually individualize screening and figure out who should get that mammogram every other year versus who should we be getting a mammogram and an M R I on and, and who should start younger and who can start later in life. So this is actually a really cool study that's going on right now. It's called The Wisdom Study. It started at UCSF. However, it is a nationwide study and you do not have to get your imaging done at a UCSF facility to participate. And you actually don't need to speak with a research coordinator. You can just go to this website that's on the bottom of this page called the Wisdom study dot org. As a patient and read through and see if it sounds interesting to you. And if it is, you can sign yourself up and then someone will contact you to talk through. What does this study mean? And essentially what we're looking at is trying to answer this question. Should we really all be getting a mammogram every single year or should our screening be based on personal risk factors? And so what this study does is it allows you to say as the patient that you're either comfortable with the trial, randomizing you to how to screen or it allows you to say, hey, I'm willing for you to watch how I screen my body and what happens to me. But I'm gonna screen. However, I want to screen, you're just not going to tell me how to do it. So you can join either arm of that. And within the study, they do things like some minimal genetic testing. They answer lots of questions about when was your first period? Have you gone through menopause all of different factors that we know can take into account for patients risk, including their family history and it spits out, you know, kind of their recommendation on. Okay, we think you should actually start at 50 and go every other year like U S P S T F said Currently versus we actually think you have some risk factors that make us want to screen you at 40 and with mammogram every single year or adding an MRI or different screening factors. So our hope is that this study will eventually show lots and lots of women participating and allow us to figure out who's what bucket and how can we actually individualize screening? We're certainly not there yet. So the next thing that I wanted to talk about is um something that I think has changed a lot in breast surgery on the benign side and that's with our high risk lesions. So we all know that we can have lots of findings on imaging that will come back with a wide variety of something that's truly benign, something that's truly cancer. And then this very large category of things that are sort of in the middle, are they actually pre cancer? Are they something that causes us to say, maybe we're at heightened risk for breast cancer, but maybe not right at that spot. And we're learning a lot more about these. So I would say in the past, we used to lump all of these together every single thing on this, on this form used to or on the slide, used to be something that we would consider high risk. And as surgeons we would recommend excising. Well, what I'm going to show you is that our data has actually shown that everything in that right hand column lobular carcinoma insitu that is classic atypical lobular hyperplasia. Or if you sometimes will see it read on a path report as atypical lobular nia play Asia um introductory popular without a tibia, radial scars or radial sclerosing lesions at all. Those are all findings that we're finding in data is showing us that we are sitting at a little higher risk of getting breast cancer somewhere in either breast when we have a finding like this, but not specifically right at that site. So they're considered something that we need to be as breast surgeons. We need to be seeing these patients regularly. We need to be screening them a little closer with mammogram and M R I and, and talking about ways to reduce risk, but we may not actually be recommending surgery for these patients unless we follow something like this and it decides to change, which is quite rare. Contrary, on the left hand side of the three different types of truly abnormal or pre cancerous things that we really know that some of these are going to actually potentially form a cancer at this spot, could have a cancer at this spot. And maybe the biopsy was just done right on the side of it. And these are actually things that when we see this as a surgeon, we recommend surgical engine to make sure that it's out, it can't change into anything. And we prove that there isn't something there more worrisome right now, some briefly touch on those three things. Um And again, this just goes through what was the past and what is the current future, the past is that we really used to excise all of these. And the current future is many of these things don't actually need to be excised yet these patients need to be followed for high risk. So one of the three that we really still recommend excision and treating as a true pre cancer right at that site is something called nonclassical lobular carcinoma insitu or you may actually see this being called as polymorphic lobular carcinoma insitu. So here's just an example of a study where there were 75 patients, 76 core biopsies that all got excised. The median age was 56 years. And all of these were considered a suspicious lesion on my biography. Most of these are gonna show up as calcium deposits like polymorphic calcifications in a kind of a grouped area or a linear area in the breast and not considered suspicious by rides for means suspicious enough where the radiologist is going to recommend a needle biopsy. And after needle biopsy, we saw Liam or fix or non classic lobby. Snowman say to. And when we took these patients, two surgery in this study, we found that 36% of them actually had malignancy. So 17 of those had an invasive breast cancer and 10 of those had ductal carcinoma insight to. And that is actually something that's quite concerning, right. You gotta didn't actually show cancer, but 36% of the people actually had cancer present. And that really is a presence of. We really need to get that area out to prove there is or is not cancer there. Right now, there was not really a radiologic or pathologic feature that predicted this upgrade. So we really didn't see through this study a way to separate out, okay. These people that have these features need excision versus those, don't? It really was all comers kind of looked the same. And in this study, patients were treated with mastectomy, they were treated with lumpectomy plus radiation and some were treated with lumpectomy alone. And that a medium follow up of 58 months, one patient or 4% um that it had an excision alone developed and it's a lateral ductal carcinoma in side to which is, which is within our range of what we would expect local recurrence to be if we do a lumpectomy alone without radiation, which is something we'll talk about much later. So the conclusion here was that we really do not feel that non classic L C I S can be left alone if it is non classic polymorphic, it really does need to be excised. Similarly, with atypical ductal hyperplasia. This is truly an abnormality within the duct that could be on it's way to forming ductal carcinoma insight to or invasive breast cancer. So, in this study, we looked at 100 and 41 surgical excisions for atypical ductal hyperplasia found on a core needle biopsy. And when these patients were taken to the operating room, we had uh this study showed 29% of patients actually had ductal carcinoma in side to right now And about 8% had an invasive breast cancer where the biopsy was probably done right on the edge of the disease. It only showed the ATPA however, slightly distant to it actually was an invasive breast cancer. So the upgrade rate was statistically lower if considered certain findings. Meaning if what you saw on your mammogram was completely removed with the core biopsy. If you had a lesion, that was bi rads, say three, the radiologist called it a three. And then six months later, they came back and they actually had maybe a couple more calcifications, but it really wasn't super suspicious. But the reason they biopsied it was because it had slightly changed, um that is something that was maybe had less of a upgrade rate to cancer If the size of the lesion was less than 1.5 cm and the patients were actually younger, it was less chance that there was a breast cancer there right then. But the overall conclusions from this study showed that the upgrade rate of 80 h to DCIS or invasive breast cancer is high. And as already known surgery should be recommended. And really, we shouldn't be, um we shouldn't be watching these. Now, this also caveat and to say that if you met all of these other criteria and in a multidisciplinary meeting, some of these other things made it look like it was a much less suspicious finding for A D H. You could consider talking with patients about showing them that they might have a lower upgrade rate to cancer and maybe follow it. And if it doesn't change, maybe it doesn't need to be exist. But this study did not globally think that that was safe for all commerce with A D H. And then this study looked at introduction papilloma with a tipi A. So, you know, again, we used to group all introductory papilloma as high risk lesions. And then there's been studies in the, in the past that have shown that if there wasn't tippy a compared to there was a tibia, there was quite a difference and upgrade rate to cancer at the time of excision. So this study looked at 259 patients, they were grouped in papilloma without A T P A and papilloma with a tibia and they even broke down the A T P A of, did it happen with atypical ductal hyperplasia or atypical lobular hyperplasia? And after a core needle biopsy that showed this with a tibia and that was with a TH or A L H surgical excision yielded a diagnosis of concomitant invasive ductal carcinoma insitu in greater than 30% of cases. However, If there was no a tip beyond the core biopsy, the likelihood of cancer was much lower. And some of the newer studies are saying definitely around less than 5% chance that there's a cancer there right now or could become something in the future if there's no a tibia there. So the conclusion from this study showed that surgical excision really should still be considered with an introductory papilloma if there's a typical findings on the core biopsy. And even if you exercise this and a finding of introductory papilloma with a tip, just also tells us that we are at higher risk for developing cancer. So if you excise it and there's no cancer there right now, we really should be following these patients from a high risk perspective and talking to them about ways to reduce the risk, even potentially with chemo prevention, taking tamoxifen. So I'm just gonna switch gears just a tiny bit and get into the cancer discussion. So, you know, standard of care for a cancer diagnosis as we, as we probably all know is a perk you tania's biopsy. If lesion looks suspicious on mammogram, ultrasound M R I or even by palpitation, you know, rarely we'll see imaging that looks normal and yet it just really does not feel normal and it just makes us very concerned that there's truly something going on. We may end up doing a biopsy. Biopsies can be done many different ways. Typically, this per Catania's is either done as a fine needle aspiration or as a core needle biopsy, core needle biopsies. A finding is only seen on mammogram like calcifications where we don't see that anywhere else, then you're going to see a recommendation for steri attacked IQ biopsy. If the lesion can be seen on ultrasound, we're going to do an ultrasound guided core biopsy. And if they're not seen on mammo or ultrasound, and it's really found as sort of an area of enhancement on M R I, then you're going to see a recommendation for M R I guided core biopsy. We typically reserve fine needle aspirations for lymph nodes. So um and there are lots of places that are doing core needle biopsies for lymph nodes in the armpit in addition and just doing everything via core, but you absolutely can get all of the information that you need from a lymph node biopsy off of a fine needle aspiration. We often are not doing fine needle aspirations for breast lesions, if we're really needing all of the stains and the receptors that we need. Although it is possible to get all of those if you get a really good sample on a fine needle aspiration. So what's going to happen if we find something that looks suspicious? Well, you're gonna, you know, you're going to find it either through history, talking the patient or through physical exam or through sending the patient for their screening mammography. Now, if you feel something, you're going to order a diagnostic mammogram because you want the radiologist to actually know where you're concerned about and they want to focus in on that area. In addition to looking at the whole breast, they want to focus in on that area that you're concerned about and likely will also ultrasound that area. You may need to do a breast M R I. But I will say there are special considerations and there are times where, you know, we say the mammogram and ultrasound really looks to be giving us the full picture and it doesn't appear that we need an M R I versus a situation where the exam is not really that consistent or the mammogram looks very different than the ultrasound or something where we're really concerned that we really, um we really need a bit more information. We're going to get a breast M R I to see what the enhancement pattern looks like. You're gonna get pathology review which is going to determine not only that it is breast cancer, but also what type of breast cancer is it? Is it hormone receptor positive? Is it her two positive? Um lots of different features we can find from the core biopsy that helps us figure out kind of who needs what treatment and how can we individualize that treatment? You might see us recommend genetic counseling. Um if somebody is diagnosed with breast cancer young or they have other family members that had breast or ovarian or pancreas cancer or even melanoma, some of the other cancers that go along with breast cancer and syndromes. We're gonna be recommending genetic testing because that may impact what a patient decides to do to not only treat their cancer but prevent a future cancer and can also give a really good picture to the whole family about where does their risk sit for getting breast cancer since mom or sister or cousin just got breast cancer. We definitely talk with our young patients about addressing fertility concerns and we talk with all of our patients about sexual health concerns because some of the medications that we put patients through will change their sexual health. And that is a huge deal for, you know, moving past this diagnosis, once their treatments are complete or even during treatments, we talk to women about, you know, is there a desire for future pregnancy and how can we help them get to that point? Whether that's going through fertility or going on medications to block the ovaries, to protect the ovaries during treatments. Um, lots of different options and we also assess patients for distress and get them in with psycho oncology and other therapies and group sessions and social work and lots of different things that come about. Um, and then, you know, really for the majority of patients diagnosed with breast cancer, a lot of them do not end up getting or needing staging studies for the whole body. But if there are any concerning symptoms um that they might have something distant metastatic or their local diseases quite progressed. And we worry, could this have gotten somewhere else or sometimes on clinical trials, we really need to prove for sure that they're not metastatic before allowing them to go on a clinical trial. Those are patients that are going to get either a pet scan or a CT scan and a bone scan. Um to be sure that we know exactly where this is at and you're going to see lots of patients needing a whole team of physicians and um colleagues in this space to really, you know, comprehensively get them through this diagnosis treatment and moving forward. So, treatment really, you know, the conversation with the patient really is typically about understanding not only the disease, but how do we consider both local and systemic therapy, which some patients will need everything and some patients will not need everything. So really, you know, describe the local therapy for breast cancer is the treatment of the disease in the breast and the regional lymph nodes that is truly local. And that's how we use surgery and radiation to focus on treatment locally. But we really have to think about systemic treatment as well because we know that for invasive breast cancer, even if we caught it early and we don't expect that it's gone somewhere else in the body. We do a scan and show that it's anywhere else in the body. We know that these cancers can decide to get into our system. And we're not smart enough today to find one single cell floating around somewhere. So we really need to focus on the biology of the cancer to decide who really needs chemotherapy to help minimize risk of recurrence or treat something that we worry could go somewhere versus who can avoid chemotherapy and maybe only need to take endocrine therapy or pills or who should we really be focusing on these immuno therapies which are much newer, much different treatments, not chemotherapies, but can be more targeted potentially to their actual specific specific disease. And you know, the thing that I think sometimes patients get confused about is these are not interchangeable treatments. You know, while somebody doesn't necessarily always need all of these treatments, it's not like, oh, if I take radiation, I won't need chemotherapy or vice versa. These are all treatments that we look actually about how to package this entire deal to really focus on treating their specific cancer so that we are very specific um and not treating their peasants cancer, that might have been very different. And again, not everyone needs every single treatment. So we've come a long way in individualizing therapy specifically on the systemic therapy side. So for the hormone positive patient, which is about 70-75% of all breast cancers, we often will do some genomic testing, which looks at the DNA of the cancer, not the patients DNA. Okay. And so really what we found in all of our studies is that clinical risk is one thing and biological risk is another and biology always wins, we can be really good at screening and picking up a really small cancer that didn't spread to a lymph node. And guess what? Some of those patients, if we don't treat them aggressively, if they have an aggressive biologic cancer are going to have a high risk of this coming back and it can come back locally or it can come back distant. It's the distant metastatic disease that we're really trying to avoid. So really knowing the biology and having a better assessment of who's going to potentially turn into that distant metastatic disease allows us to up front, treat with things to help minimize that. So we look at staging, which used to all be an atomic, how big was it, what is it in the lymph node status or not? And do we think it's gone somewhere? Now, we actually add biological factors to our staging studies. So we add the grade, we add the hormone receptor status. If we've done one of these genomic tests like uncle type or ma'am a print, then we add that result in and it might say that, hey, this looks like a really bigger cancer that spread to a lymph node. But actually, it's acting like a stage one, breast cancer and it really doesn't need all the bells and whistles to treat it and make it not come back as opposed to that other person I was describing who had maybe the really small answer that hadn't spread, but it's grade three and it's triple negative and it's got all these other factors about it that just make it want to come back that we really need to say this is a higher stage because biologically it is more aggressive and we need more treatments for it because then we can help reduce it's chance from coming back. So that's sort of how we use these genomic testing. Um And again, we have, you know, the two tests on the market and to type and mama print, there's other tests, I'm sure that are coming down the pike. There's a few newer ones that people are starting to use. Their all have a similar goal. They look at the D N a of the cancer cells from either a core biopsy or from a surgical specimen and they come back with a risk score. What is the chance that this is going to come back? And that's what we say, if it's high risk or you're really young and it's intermediate risk, you're going to need some chemotherapy to help make this not come back. There's other types of receptors that really we don't need the genomic testing because we know more about the biology due to the receptor status. So for example, a her two targeted or a her two positive cancer, it really actually needs to targeted therapies. You know, this used to be a really nasty cancer to get in the past weeks to see tons and tons of recurrences with her two positive cancer. Well, then Herceptin was invented and now we have tons of other medications, Pirjeta TDM one and her two. There's so many different targeted her to therapies and these are not chemotherapy. The these are antibody therapy, monoclonal antibody therapy and some immuno therapies that are targeted and sometimes tagged with chemotherapy to make the most effective. But they are given to really attack that two receptor and make it so that patients have a super high chance of making this not come back really low recurrence risks if they respond great. Similar and also different is the triple negative cancer where the estrogen progesterone and the her two receptor are not found and there's a wide difference of types of triple negative cancers that we're learning about it. They're not all, even the same bag, some are immune positive, some are immune positive. You know, there's lots of different categories. However, again, in our studies, we're learning about some of these immuno therapies, some of these immuno therapies are coming on the market. FDA approved can be given to patients with triple negative breast cancer to give them a much better outcome for effective treatment today and reduce risk of recurrence in the future. Now, certainly we know that some patients unfortunately are going to present with metastatic breast cancer distant in their body, either at the time of diagnosis or as a recurrence. And these, these are treated quite different than somebody where we are treating for a cure. You know, the good thing about metastatic breast cancer is that we do have some really effective systemic therapy to make this disease be something that patients can still live with for a very long time. Certainly there are types of breast cancers that patients don't live very long. That is really our focus in studies for metastatic patients is trying to give patients not only a long life but a better quality of life. So we have, you know, for the hormone receptor positive patient, we often do not do chemotherapy. We start with pill That block the hormone receptor and we add boosters to those the CDK- 46 inhibitors that can, you know, stimulate and make those endocrine therapy treatments a bit stronger and potentially try to last longer. So that we are not getting to the point where we are progressing on disease and having to change through treatment that quickly. Now, unfortunately, if we are her two positive or triple negative, we are still going to need some chemotherapy, maybe immunotherapy, maybe the her two targeted drugs which are ivy um even for metastatic. But we just look at giving treatment a bit differently so that we can extend the length and options of treatment available for these patients. We also have newer systemic therapies for patients that are backup positive, which makes genetic testing even more important. It's not only a surgical thing anymore if we know we're back up positive and we add these, some of these parts inhibitors elaborate is just one of them. Um sometimes we can give patients a much better outcome long term. So there's a lot of things coming down the pike. So again, you know the question of how should we give chemotherapy or not? We kind of discussed. But what about the question of when should we give chemotherapy? Should we be giving chemotherapy after surgery? Should we be giving chemotherapy before surgery and the neo adjuvant setting? And a lot of times we're using the information about, well, how big is the tumor? And is there a lymph node positive? And are there things that neo adjuvant treatment would help if it shrinks appropriately, would help us do smaller surgery or do less. That is a reason to give neo adjuvant therapy. But there's lots of other reasons including things like, well, if the tumor is there and you can watch the tumor shrink, you can make sure that the drugs that you're giving are actually working for the patient. And if they're not working or it's progressing on the medications, you can actually make a switch, whether that's to stop chemo and go to surgery or whether that's to switch chemotherapies and more targeted therapies. You can also take data that was taken out of neo adjuvant trials in the past and say, well, if we give you this chemotherapy and we go to surgery and the cancer is all gone, we feel very confident that you don't need any other medication or we don't need to change anything with your regimen because you had such a great response compared to the person who maybe had a response. But it was only a partial response that lymph node was still positive or we still had two centimeters of disease in the breast. Even after all that chemo, we got, we have some really great data that says, well, in that patient, if we add this drug or we change to that drug, we can actually give them a lower risk of recurrent. So, so many reasons to consider neo adjuvant therapy. If we know someone is gonna need chemotherapy to begin with. And just a quick brief moment about one of our big neo adjuvant trials that started at UCSF but is a nationwide trial going on right now called the I Spy Clinical Trial. This is exactly what we're doing. We're finding patients that need chemo chemotherapy and we're randomizing them to different arms according to their receptor status and different factors that we know about from the core biopsy. And we're checking, we're trying to switch the way that we give medication to give more targeted therapies up front. And if we get to the point where those targeted therapies make that cancer completely go away. Maybe we can deescalate and not have to get stronger chemotherapies that were used that our current standard of care gives versus proving that hey, if these other things are not making this go away effectively, we actually really, this cancer really needs full court press, it really needs those stronger medications. So everything allows us individualize the treatment to the patient. Totally switch gears and step away from systemic therapy and kind of come into my realm, which is the evolution of breast surgery, not to go into too much detail. And thankfully, we're not doing this anymore, but we used to start with a radical mastectomy where we will remove the whole breast, all the lymph nodes, all the muscles, everything. And thankfully, that is not something we're doing any further because of this N A C B P B O for trial, which looked at the radical mastectomy. And compared it to what we call a total mastectomy or a mastectomy where we removed the breast and all the lymph nodes. But we do not remove any of the muscle. And in this, in this, in this study, actually, we only removed the lymph nodes or they only remove the lymph nodes if the patients had a palpable lymph nodes. So if a patient did not have a palpable lymph node in this study, which was many, many years ago, those patients would just have had a mastectomy, no lymph node dissection and the patients that had the palpable node had the breast and the lymph nodes. But in both cases, all muscle left intact and guess what? There was no difference in disease free survival, relapse free survival, distant disease free survival, overall survival. You know, all of the good things, everything looked like this was equivalent to treat these cancers. So then we said, okay, well, what if we really actually don't need to remove the whole breast? You know, some of these women were presenting with really big breast cancers and maybe they did need a mastectomy. But some of these women were popping up with a palpable lump that was two centimeters just close to the skin. And maybe they didn't really need their whole breast to be removed. And that was the N S A B P B 06 trial where this looked at the total mastectomy and compared it to the lumpectomy for women that had less than four centimeter tumor. In this study, all women had an axillary dissection. And what we saw was there was absolutely no difference in disease free, distant disease free or overall survival in the groups. And there was a significant decrease in local recurrence rates if we gave the lumpectomy with radiation. So they kind of studied two things. Can we safely do a lumpectomy and not just do a mastectomy for everyone? And the answer was yes. And what they found was there was a higher local recurrence rate when we compared mastectomy to Olympic in the lumpectomy arm. So removing only part of the breast gave you a higher risk of local recurrence. But when we added radiation to that, it equaled that of a mastectomy in long term local recurrence. Um chances. So that actually got us to where we are today being able to offer women lumpectomy and oftentimes with radiation. Now there's been a huge change in axillary surgery. So again, back in those studies that were looking either no axillary surgery or axillary dissection for every single patient, we then studied the sentinel lymph node. So we said okay, if you were clinically lymph node negative, could we just map using a tracer your lymphatic channels in your breast that travel up and get stuck on your first draining sentinel lymph node. Sentinel just means first doesn't mean one. And if we took that lymph node out and it was negative. And then in this study, we took all your lymph nodes out and the rest of them were negative. How accurate was it that if we just did the sentinel node and left the rest of those nodes there, what would happen? So first, we proved that we could do a sentinel node. And then we did this study called the Z 11. And Z 11 was a study that was very instrumental um to the change in breast surgery from axillary dissection to sentinel node. Because what happened was we said, not only is it safe to do a sentinel lymph node biopsy, but if you were clinically lymph node negative, so those lymph nodes felt normal and you went to surgery and we found one or even two lymph nodes that had breast cancer in the lymph node. And it was inside the lymph node and it had not broken through the wall of the capsule of the lymph node. Yet, could we stop there? Or would we actually need to do an accelerated section for all patients that still had that had a positive node? And what we found in that study is that if you only had one lymph node or to lymph nodes, and it hadn't broken through the wall of the lymph node, there was no difference in recurrence, whether you had an axillary dissection or you didn't have any further surgery. And that's why today you see many, many times if the clinically, if the lymph nodes are clinically negative and a patient gets taken to surgery and they have a central node biopsy and one or two lymph nodes are positive. You will see these patients not be taken back to the operating room because there is no data that says they need to go back and they're going to do better if they go back. So that Z11 study was only studied in lumpectomy patients. And one of the criticisms of that study was that well, most lumpectomy patients get radiation. And so how can you say that this is okay to leave a positive, you know, not go back and do an excellent dissection for patients that had a positive lymph node. If you did a mastectomy, can we really truly extrapolate that data to patients that have a mastectomy because a lot of mastectomy patients don't have radiation? So, what did we do? Then we studied this question and mastectomy and this is called the Amaro's trial. And similar criteria. Patients had a lymph node that looked normal, they went to surgery, they had a sentinel node biopsy. In this study, it let them have up to three lymph nodes positive. And what they studied was the clinical difference between, well, what if we just gave them some radiation compared to having an axillary dissection? And we found no difference in local recurrence, distant recurrence and survival between radiation to that area versus axillary dissection. So now what you're seeing is patients will even go for mastectomy. And if they have one or two or three positive notes, we often are not taking them back for axillary dissection because we know they gain benefit from having radiation. And if we radiate up into their armpit, they have less morbidity, less problems with range of motion, lymphedema problems with scar tissue. If we take and allow radiation to take care of it, as opposed to taking someone for an axillary dissection. Now we started studying then the patients that have neo adjuvant therapy because now a lot of times our patients are having neo adjuvant chemotherapy. And we're saying well, okay that Z 11 and the ambrose trial were only in patients that had small burden of disease where you just took them for surgery up front. What happens if you actually go and you do um chemotherapy? And then first we had to prove that if we did chemotherapy, we could still accurately find the Sentinel notes that chemotherapy was not going to mess up our lymphatic channels and the drainage patterns to accurately find the sentinel node. And so the idea to trial was actually that exact trial looking at a sentinel node after chemotherapy in the clinically node, negative patients who maybe they got chemotherapy because their breast tumor was very large, but they're lymph node was negative and they shrunk it down with chemo and then we took them to surgery for either lumpectomy or mastectomy. And we were able to prove that yes, you can still safely map the Sentinel node and accurately do that. You do not need to do an axillary dissection in that case just because they had chemo. So then came the Z1071 study where we said, Okay. Well, what if the patient had a positive lymph node? And you gave chemotherapy and through chemotherapy that lymph node became negative. So they were positive pathologically before, but they became clinically lymph node negative. Would you have to do an axillary dissection in that perspective? Or could you safely do a sentinel node and say that if you got some lymph nodes out that and they were negative that you could safely stop there? What that study showed was that if the biopsy proven node had a clip in it and you removed the clipped node and you got at least two ideally three total nodes out that if all of those lymph nodes were negative and then in that study, they went and did the full axillary dissection to prove were any of the other lymph nodes positive? The risk of having residual positive nodes if three or were negative when you took them out, including the clipped node was extremely low was like less than 9%. And so they thought that that was their crushed threshold was under 10%. And that though, that basically was kind of instrumental in saying that yes, if you used to have a positive note, but chemo work so well against your cancer to make that lymph node negative, that you don't actually gain benefit. There's no recurrence decrease if we go and take an axillary dissection versus actually just removing the central node and stopping there. So currently there are two trials that are going on to answer even a further question of what about if the lymph nodes remain positive? So the lymph node was positive to begin with and they become clinically lymph node negative and clinically lymph node negative means that you don't feel them anymore. Okay, then you go to the operating room and actually pathologically, the lymph node is still positive. Okay. This is the A 112 oh two trial. In this trial, we were we are randomizing patients to say okay if it's still positive. One arm of the trial is current standard of care, which is axillary dissection plus radiation. And one arm of the trial is saying, okay, just don't do any more surgery and deliver axillary radiation. And we're trying to see if axillary radiation is equivalent to axillary dissection plus radiation. And if it is which again, some of our radiation trials would say that if disease is not grossly palpable, if it's truly microscopic radiation may be equivalent and may be able to take care of that without putting patients through extensive axillary surgery. The B 51 trial on the other hand, is looking at patients that had a node positive became clinically, node negative went to the operating room and were found to have negative lymph nodes. So in that study there then saying okay, well, if they're already negative from chemo, can we avoid radiation? Can we make it so that we actually don't have to do any further treatment to the axle A? Because in Z 10 71 they were still radiating Taxila and treating that previously positive nodal area. So these are studies that are coming down the pike that are very exciting that we are feeling like will help us really own in on how do we truly individualize who needs what and how do we deescalate? The last thing to talk about with this nodal de escalation is our American Society of breast surgeons choosing wisely, which basically is a consensus statement Talking about certain populations of patients where maybe we can actually omit the nodal evaluation completely and only take care of what's going on in the breast. And this was really looking at women who have small burden of disease, like less than two cm of hormone receptor positive and her two negative cancer That are clinically lymph node negative. And these were looking at women over 65 years old who were going to go for a lumpectomy and who planned on taking endocrine therapy and we looked at, you know, does knowing the nodal status in that situation, does it actually make a huge impact on whether or not a medical oncologist would give someone like that chemotherapy? Would we give more radiation? Would it change any of our treatments or not? And essentially what we found was that even if you don't remove a node, you can still do the genomic testing on the breast cancer from the breast itself to be able to answer that question of. Should I do chemotherapy or can I just give endocrine therapy? And you can still make decisions on radiation without the nodal status, knowing that the node is clinically negative. So this is sort of where we're at today. Um Now we've also made some advancements in radiation. We've made lots of advancements in lots of different fields of breast cancer. But this is a really exciting trial called the prime to trial that looked at 1326 women, age 65 and older with that early stage breast cancer, similar to what I was just describing hormone receptor positive, clinically axillary lymph node negative. In this study, they looked at tumors up to three cm that were excised with clear margins with a lumpectomy. They could have grade three tumor or they could have lymphoma vascular invasion, but they couldn't have both of those high risk factors. And they again was breast conserving surgery who were going to receive adjuvant endocrine therapy and what they randomized these women to was receiving radiation versus omitting radiation. And this here talks about the five year follow up, but we recently just got the 10 year follow up. And what this showed was after five years. If you had radiation, You had a very low risk of recurrence 1.3%. And if you didn't have radiation, it was higher, it was at 4%. But 4% means that 96% of people didn't recur locally in the breast. And the biggest important factor about this was radiation did not have any impact on whether you developed regional recurrence, distant metastases, contra lateral breast cancer or completely new breast cancer. Now, the 10 year data says that if you have no radiation and you're on endocrine therapy, you have about a 10% risk of local recurrence in the breast. And that's compared to just under 5% for the patients that get radiation, they have about a 4% risk. However, again, that still stood up that there was no difference in regional recurrence, no difference in distant metastases, no difference in contra lateral breast cancer. And so, you know, this really becomes a discussion with these elderly patients about, you know, how aggressive do you want to get and how comfortable are you with these numbers and these risk factors um to decide, you know, should I have radiation or should I not have radiation once it's been taken out? Um kind of switching gears slightly to prevention. You know, there are data that show that there are things that we can do to also reduce our risk forever getting breast cancer or reduce our risk for getting recurrence. There are lifestyle modifications and these have been studied showing that if we can get about three hours of moderate exercise a week and that's like walking, hiking, yoga, things that we're moving our body, but we're not necessarily sweating and really out of breath. Or if we are doing things like spinning and kickboxing and running and hit classes and things that make us really out of breath if we focus on 75 minutes a week And we eat that quote unquote healthy Mediterranean style diet with minimizing our processed foods, minimizing our sugars. And we make those choices about 80% of the time. If we don't smoke, we limit alcohol to less than, you know, one drink per day. Ideally, three times per week, all of these things have been shown in studies to reduce our risk of getting breast cancer. And that diet and exercise. Actually, that study came out a cup Four years ago showing about almost a 30-40% lifetime risk reduction of breast cancer by doing that type of exercise and diet, which is super impactful and something that patients can really, um kind of grasp onto and feel comfortable, right, that they can actually do something about it. Now, we also talk to patients about genetics for risk reduction. So, you know, we really like to assess patients family history and personal history to figure out are there any red flags that make us feel really strongly that there could be a genetic mutation in this family or maybe a family member that got breast cancer, got genetic testing and was positive. And they found out that, hey, actually, now I need to be tested and I have the gene that my mom or my Sister Hat. And so we can do panel testing. We can, you know, we can, it's always best to test the affected family member if possible if that person is living and willing because if they got their breast cancer at 35 and they don't have a genetic mutation and there's nobody else that had breast cancer. It's unlikely that there's a genetic mutation in the family. But if family members are not willing or not able to be tested, then our patient whose family met the criteria to be tested, our patient can be tested and we can do some panel testing and figure out do they actually sit at a significantly higher risk of getting breast cancer because of gene mutation in their D N A, which is maybe there's a risk option from either surgery or taking pills. Um And this is actually kind of an interesting study in a week we had, I think most of us probably know about the star trial which looked at um full dose 20 mg tamoxifen um taken for five years. Um and it showed a 50% risk reduction for getting breast cancer lifetime for patients that took that. But 20 mg of tamoxifen a day and cause a lot of side effects for patients and can cause some scary side effects that can cause DVT and other things. So what we did recently is we studied well. What if I mean, these patients have never had cancer? What if we studied a five mg dose for three years daily instead of 20 mg for five years. And we saw about a 48% lifetime risk reduction. So almost 50% risk reduction with the low dose tamoxifen. And yet when we looked at low dose tamoxifen versus placebo, there were very, very, very low amount of side effects. There were really no differences from placebo with hot flashes, there was one DVT and one endometrial cancer in the low dose Tamoxifen arm and there was one pe in the placebo arm. So this was felt to be probably not significant DVT risk for the low dose tamoxifen. But there still was that one patient that got endometrial hyperplasia. So anyone that's going on even low dose tamoxifen, we will have C N O B G Y N annually and just make sure that if they're having any set of bleeding or any issues that they get evaluated immediately. And I think that's where I'm going to stop here. I will pull up the Q and A but just a real brief slide about sort of who we are over the Berkeley Outpatient Center. We, you know, we are an extension of our clinical services at Mission Bay. We are the UCSF Cancer Center at the Berkeley Outpatient Center. We see patients with all type cancers for our medical oncologists and then from a surgical perspective there, um as Dr Abe and myself are the breast surgeons and we recently since we just moved into our bigger space, have some of our other oncological surgeons coming over to the East Bay such as gynecological oncology, some of our head and neck surgeons Ortho oncology. They, there's um a bunch of different specialists in the Berkeley Outpatient Center to help patients try to have access and potentially be closer to home if they're, if they live in the East Bay or, or coming from that direction, Dr Malhotra is a gi oncology but sees a bunch of different types of oncology. And Dr Marshall is our medical oncologist for breast cancer over the Berkeley Outpatient center. And I'll just leave this up while we do the Q and A so that um if you need my contact information, I'm happy to answer questions any time, please feel free to email or call me. This is my cell phone on here on the left hand side of the screen. Um And then certainly patients can be, can find us either by phone um under the Berkeley Outpatient Center or I put our Q R code because patients can actually self schedule with us, which is really helpful in this day and age. If you snap a picture of that, um, they can actually just self schedule.
