Latest / Behind The Knife: The Surgery Podcast / Clinical Challenges in Breast Surgery: The Management of Ductal Carcinoma In Situ (DCIS)
Transcript
- Management of DCIS === [00:00:00] Hello everyone. Welcome to the Breast Specialty Podcast series. This is Behind the Knife. I'm Rashmi Kumar, your resident host for today. I'm a current general surgery resident at the University of Michigan. We're so glad to have you join us as we dive into the nuances of DCIS. Before we start, I'd like to introduce our two outstanding guests. First we have Dr. Melissa Poluski, attending and breast surgical oncologist at the University of Michigan. She also serves as the co-director of the Wiser Family Center for Breast Care. Thank you so much, Dr. Poluski, for joining us. Thank you, Rashmi, for the invitation. It's great to be here today. We're also joined by Dr. Stephanie Down scanner, breast surgical oncologist and physician scientist at Memorial Sloan Kettering Cancer Center. Dr. Down Scanner is also the current program director of the Breast Fellowship training program there. Thanks for joining us, Dr. Down Scanner. Great to be with you both today, and I am sitting right here in Dr. Polowski's old office. Thank you for that fun fact. Let's start with the [00:01:00] basics today and define DCIS first ductal carcinoma, and C two is most simply defined as non-invasive breast cancer. To understand that definition, I think we have to look at where DCIS originates in the breast. DCIS originates in the terminal ductal lobular unit, which is where milk is produced. The epithelial cells lining in the milk duct are separated from surrounding tissue by a basement membrane. In DCIS, the malignant cells are confined to this basement membrane, which is why it's called NC two, or in place when cells invade past the basement membrane. We call that invasive breast cancer. So DCIS is a potential precursor to invasive disease, but even the definition of DCIS isn't always straightforward. Dr. Poluski, could you explain why DCIS can be tricky to define and how you discuss the diagnosis with your patients? Yeah, thanks, Rashmi. I think that this is one of the more challenging conversations that I [00:02:00] have with patients in clinic. DCIS, by definition, is staged as stage zero breast cancer. And when we're using the term cancer, we often think about cells that have the potential to spread. To go to lymph nodes or elsewhere in the body. But we know that DCIS by itself doesn't have that potential at first, has to become an invasive process. And so I often tell people that this could be labeled as stage zero breast cancer or preinvasive changes within the breast, and that we're talking about the same thing. And that not all DCIS will become an invasive cancer. So we term this as a non obligate precursor. It has the potential to become an invasive cancer, but right now we don't know which is which, which DCIS should we care about that has that risk, and which is something that potentially could stay contained within the milk duct for the rest of that individual's life. That's really helpful perspective for our listeners. DCIS was last covered in depth in a great episode in 2022 by the [00:03:00] UCSF breast surgery team. We're building on their discussion, especially given how rapidly the management for DCIS is evolving and the number of clinical trials studying DCIS patients. Let's talk about numbers. Each year about 60,000 women are diagnosed with DCIS annually. Making up to nearly a quarter of all the breast cancer diagnoses in the country as women age, particularly after 50, the incidents also rises with each decade, Dr. Down scanner. Can you connect the dots for us between the rise of screening mammography and the DCIS diagnoses? Sure. That's a great question. Fortunately, we have screening mammography, which is really useful at early detection and when cancers are detected earlier, the outcomes are better regarding DCIS. About 90% of DCIS cases are diagnosed on a patient's screening mammogram, meaning they're asymptomatic. They don't have a lump or nipple discharge or breast changes. For this reason, we've [00:04:00] seen a serious increase in the diagnosis of DCIS prior to the routine use of screening mammography. That incidents of DCIS was about 1.5 in every 100,000 women. But now it's closer to 35 cases per 100,000 women. This is not because DCIS is rapidly on the rise, but rather because of the concept that Dr. Pki mentioned that it is a non obligate precursor. So all of these women probably also had DCIS before the advent of screening mammography, but we weren't detecting it because it wasn't turning into a cancer, or perhaps they were older and going on to die of another cause. And that's a really important takeaway here. The majority of the DCIS patients, like Dr. Down scanner was saying, are found in asymptomatic women. Thanks to the routine screening that we have. This raises important questions about management and also sets the stage for our next discussion as breast surgeons. Can both of you talk a little bit about why DCIS is such a clinically [00:05:00] challenging disease? I'm happy to start here. So. One concept that I often discuss with patients is that there are two questions in my mind. What is the risk right now and what is the future risk of progression? So when we think about the risk right now, it's important to understand that when we have DCIS from a core biopsy, we have a small sample. So when there's a finding on mammogram that is then tested, we get results of. What was found in that core biopsy. But we really need pathologic analysis of the entire lesion to understand if there is an associated invasive cancer. And that's what we would term the upgrade rate. And what studies have shown is if we look at all comers of women with DCIS and a core biopsy. Upwards of 20 to 25% of those patients will have an invasive cancer at the time of surgical excision. And so that's kind of this number one question is are we missing something and would that finding change our additional recommendations for [00:06:00] treatment? The second question is, what we've kind of been focusing on is what's then the risk of progression of this DCIS lesion of becoming something more meaningful or invasive in the future. And so that's where, you know, a lot of the data is right now of how do we understand which DCIS is at risk for both of those finding. Who's at higher risk for having an upgrade to invasive cancer right now if we went to surgery, and which lesions are more likely to progress in the future? And that is really, I would say for this topic, the million dollar question. I think another concept that I try to explain to my patients that we know from historical data is that when DCIS recurs about half of all recurrences are invasive. So one thing we're also trying to do is manage both. That risk, but also the risks of the treatment that we can provide patients, that does reduce the risk of recurrence. So we want to really optimize what we're doing now to both prevent recurrence, but minimize side effects of the [00:07:00] treatments we have for our patients. You can see that this is really a complex topic with many gray areas, but we're gonna tackle those with the educational objectives for the episode. First, we'll review the current standard of care for DCIS using a straightforward case. Next, we'll highlight key decision points and DCIS risk stratification. This is going to help us inform how do we decide between different forms of adjuvant therapies. Then we'll bring in the latest. Data from the COMET trial and discuss how management of low risk DCIS may change in the future. And we'll put this in context with the second case. So let's get going and jump into our first case. Our first patient is a 45-year-old woman that has had an abnormal screening mammogram showing microcalcifications in her right breast. She has a follow-up diagnostic mammogram that reveals a two centimeter area with. Pleomorphic calcifications. This is called as Birads four in the right upper outer quadrant, four centimeters from the nipple. A [00:08:00] stereotactic core needle biopsy shows estrogen receptor positive high grade DCIS with mixed micro papillary and solid features with CTO necrosis. Let's break down the pathology here. Dr. Poluski, what should we focus on in this report? So, a few areas of important information that we can gather from the core biopsy pathology. First is the grade, and while there are a number of different grading systems that have been reported for DCIS, we typically see this broken down into low, intermediate, or high grade. Based on the nuclear appearance, mitotic rate, the architecture and presence of necrosis as handful of variables that are taken into consideration when assigning the grain. Other important features from my standpoint, when thinking about. Both treatment options and risk in the future are the hormone receptor status. Most DCIS is hormone receptor positive, which is what we see in this case as well as the presence of necrosis. Communal necrosis within [00:09:00] DCIS is an additional risk factor when we're thinking about future recurrence. Great. So takeaways here. First, notice the DCIS grade, then the hormone receptor status, and also notice any key features that may allude to more aggressive biology. The first line treatment for DCIS is surgery. So what are our surgical options for DCIS, DR Down scanner? How do we select between lumpectomy and mastectomy, and when do we consider using sentinel lymph node biopsy? Thanks, Rashmi. So correct. Surgery is the first line of therapy and patients are considered for lumpectomy versus mastectomy by many factors. One is the extent of disease, so that's what we call the tumor in this case, DCIS to breast size ratio. In some cases there are so much DCIS that. It cannot be safely removed without removing the entire breast. That would be a reason that a patient needs a mastectomy. Otherwise, patients who have contraindications to radiation [00:10:00] might be suggested to undergo mastectomy. Although for DCIS, radiation isn't required, so that's not necessarily a hard indication for mastectomy. The final. Strong indication would be patients with pathogenic mutations in hereditary breast or bearing cancer genes such as BRCA one and BRCA two. If they're diagnosed with DCIS, they may be encouraged to have a bilateral mastectomy. For most patients diagnosed with DCIS, the disease is small enough that we can consider lumpectomy, which is a much smaller surgery with less short-term and long-term side effects. It's important to note that DCIS is not a deadly disease, and so the survival outcomes are really close to a hundred percent the disease specific survival outcomes, whether a patient's treated with lumpectomy or mastectomy, while there are some differences in local recurrence, again, the disease itself is not deadly, so really there's no difference in survival. This is also true for invasive cancer as well, but that's another topic. Sentinel lymph [00:11:00] node biopsy is something we're familiar with from invasive breast cancer. This is a procedure that's used to stage the axilla, so using radioactive tracer or blue dye or other types of dye. The lymph nodes that drain the breasts are mapped and removed and checked for the presence of cancer. In patients who have DCIS, we don't routinely use a sentinel lymph node biopsy because we don't think that the DCIS. Can spread. As we've discussed, however, we know about 20% of patients will have invasive cancer when we actually excise their DCIS. And so if they're having a mastectomy and we ultimately find invasive cancer, we will have wanted to know that information. From the sentinel lymph node biopsy. The issue is that once you've done a mastectomy, it's extremely difficult to map the sentinel nodes. And if you want that information, the only way to really get it is an axillary dissection, which is quite morbid. So for this reason, when patients are undergoing mastectomy for DCIS, we'll typically check a sentinel lymph node at that time.[00:12:00] With the advent of the sound trial and other trials showing the safety of omission of sentinel lymph node biopsy in patients with early stage hormone receptor positive breast cancer, it's probably going to become less and less likely that a sentinel lymph node biopsy is checked for women undergoing mastectomy for ER-positive DCIS. And I'll defer to Dr. Poluski to talk about the use of a delayed sentinel lymph node biopsy in this setting, as I do believe she has more experience with that. Thanks. Yeah. I mean to Dr. John Scanner's point, the question here is, when would nodal information be necessary if final pathology showed an upgrade to invasive cancer? When we're performing a mastectomy, I completely agree that this is going to become less and less important given the data we have. Some caveats to take into consideration. We do know that about a quarter of DCIS may be ER negative and that. DCIS itself may be more likely to be her two positive, leaving this question of what would the receptor profile [00:13:00] of our invasive cancer be if that were to be identified. And so another option that we have when we want the potential to stage the axilla, if invasive cancer is found, is to use a different mapping technique that has a longer halflife. So there's now an option of using. Let's the term spi, super paramagnetic Iron oxide is a brand name of Mag Trace, which is a dye that can be injected at the time of the mastectomy. Maps to your sentinel nodes, but it lasts for at least 30 days. And so this allows the opportunity to map the axilla, perform the mastectomy without removal of any lymph nodes. And then in the select cases where there's an invasive upgrade found on final pathology, and it is determined that nodal staging. Would be impactful for adjuvant therapy recommendations, we can go back and remove those sentinel nodes. And so it really reduces the overall cohort of patients who have unnecessary sentinel node biopsies, but does require a return trip to the [00:14:00] operating room for those select patients where we think that this would be useful. Thank you both for walking us so clearly through that and also talking about the newer possibilities of delayed mapping, which is starting to become prevalent in some centers. So next I wanna talk about what the patient opts for. So after our discussion, the patient elects to undergo a lumpectomy. Her final surgical pathology post excision is still consistent with high grade DCIS. There's no evidence of invasive breast cancer. She's still er positive. There's also a final rate of PR positive in the hormone receptor status, but the medial and the lateral margins are positive. So what's next for this patient? So when we perform a lumpectomy for DCIS, it is important that we achieve. Appropriate clear margins with the goal of reducing risk of subsequent recurrence. And so there is a overview of data with a [00:15:00] consensus statement that was developed a number of years ago that reviewed the available data to identify the optimal negative margin associated with a. Reduction in future recurrence risk. And for DCIS, that magic number is two millimeters. And so, you know, I think that it's important to have a good idea when we are looking at margins, what we're actually talking about. This doesn't guarantee the complete absence of any residual microscopic disease within the breast, but it's asking at what volume of negative margins do we think that the additional. Residual disease could be controlled by adjuvant therapy and has a significant reduction in future risk. And so with positive margins in this situation, in a otherwise young, healthy person who can tolerate this, a re-excision would be recommended. And. I do in these cases where this was diagnosed by mammography, with calcifications, perform a post excision mammogram before returning [00:16:00] to the operating room so that if there are any residual calcifications around the lumpectomy bed, those can be localized and targeted at the time of re-excision. And so that would be a, a important component in. Patient's care. I would just add that when we're thinking about margins, it's also important to think about whether or not the patient's going to be getting radiation. It's a little bit more nuanced than what I think most general surgery residents would be expected to know. But a lot of patients who have DCIS don't get any radiation at all, and many do. And if we look historically at patients who got radiation. It looks like the margin width is potentially a little bit less important or not significant anymore, and this year at the American Society of Breast Surgeons, some data from one of the N-S-A-B-P studies looking at radiation for DCIS was presented and showed that a smaller margin width in patients who were getting radiated really did not have an impact on local [00:17:00] recurrence. However, these patients would need to be carefully selected and be. Committed to having radiation if they had a smaller margin width and you were considering not re excising. Thanks and I, I want to emphasize that the margin consensus statement of two millimeters is for patients having lumpectomy followed by radiation. So in patients who will decline radiation, you know, oftentimes we wanna make sure that we have at least that negative margin. And to echo what Dr. Don Canner said, there are also a couple of single institution series out of Memorial Sloan Kettering and MD Anderson that show that low volume closer margins having. You know, one margin, that's one millimeter in patients who went on to have radiation was not associated with a detriment in outcomes. And this is where there's a lot of nuanced decision making, volume of disease that's near a margin, the number of margins involved, which margin those are. Is there still residual breast in that direction?[00:18:00] Are all things that we take into consideration in addition to post excit mammogram when making that decision. But for all patients here with a positive margin, regardless of planning for adjuvant therapy, re-excision would be standard. Exactly. Thank you for that excellent summary. I think it's important to note this is a very commonly tested topic on the app site each year. So for the purposes of the app site, a two millimeter margin is required for DCIS on the test. And then in real life there are lots of considerations and clearly this is an area of active discussion and evolving study with new data from clinical trials. So please be on the lookout for that. So now that she has undergone a re-excision her final pathology for our patient shows clear two millimeter margins. What are the next options here? Let's discuss adjuvant therapies. First, we'll talk about adjuvant radiation, Dr. Down scanner. One of the things that came up in my reading in preparation for this podcast is whether radiation after lump. [00:19:00] Actually affects overall survival. If you could speak to that and also how do you decide which patients then get radiation post lumpectomy? Great question. It's a complicated topic, but the first thing that I'll emphasize, which I stated earlier, is that DCIS is not a deadly disease. So the disease specific survival is near 100%. Radiation is not going to impact survival directly. However, we know from two randomized trials. Organized and executed by the N-S-A-B-P-N-S-A-B-P-B 17 and B 24 that the addition of radiation to a lumpectomy for DCIS reduces the risk of recurrence by half. So that's a pretty good number. In general, the way I think about who I might recommend for radiation is who do I think has a high likelihood of recurrence? But I take into account a lot of factors. So are they going to live for 50 more years and they have all of this time to develop a recurrence, or are they going to live for. Five or 10 more years. Are there any reasons why [00:20:00] radiation might be particularly challenging for that patient, et cetera, et cetera? So it's really personalized to the patient, and it also depends on their own personal. Risk tolerance. For some patients, a 10% risk of recurrence feels extremely high, and for some patients that feels extremely low. We also have some clinically validated tools that help us determine these estimated risks of recurrence and potentially the benefit of radiation. On top of that, which we know is about a 50% reduction in recurrence, I personally really like to use the nomogram developed by Kim Van Z at Memorial Sloan Kettering, which takes. Some clinical factors into account to help predict the risk of recurrence, and then you can plug in whether or not the patient gets radiation and whether or not they get endocrine therapy and see what the risk of recurrence would be with those additional therapies. One challenge in DCIS is that studying what makes DCIS different from invasive cancer, what types of DCIS recur at the molecular level has been really, really [00:21:00] challenging. There is an Oncotype DCIS score. It is a 12 gene assay, which assesses the risk of recurrence of DCIS in the later breast and can help some patients and clinicians understand their risk of recurrence. The other test that's available is the Prelude DX decision, RT test. The difference in this test is that it also gives you a predicted benefit of radiation. So the Oncotype DCIS scores just predicted risk of recurrence and the Prelude DX decision. RT test is risk of recurrence, plus benefit of radiation. We've started to use that a little bit here, but I think we need certainly really good tests to help us understand the natural history of an individual patient's DCIS, and we don't have them. Thanks so much, Dr. Don Skinner. I thought it would be interesting for the purposes of the podcast for our patient to use the M-S-K-C-C nomogram to look at what is the risk of recurrence at baseline, and then how can we modify that with adjuvant radiation. So for our patient using the nomogram. [00:22:00] The five-year recurrence risk is 11%, and the 10 year recurrence risk is 18%, and this is at baseline without adjuvant therapies. If we add adjuvant radiation alone, the five-year risk is reduced from 11% to 4% and the 10 year risk. Is reduced from 18% to 7%. Before we go on to talk about endocrine therapies, I wanna discuss with Dr. Poluski any additional comments that she might have about the risk reduction. I would really echo what Dr. Don Canner said here, and I also in clinic use the Ms. KCC mammogram. Often we have found that the additional test, at least with available data, don't add whole lot more than what we can estimate based on patient age and the pathologic features that we can put into the nomogram. I would emphasize that age is strongly associated with risk of recurrence. And another point that I wanted to highlight that was previously mentioned is that when we look at these numbers here, for the 10 year risk of recurrence going from 18 to 7%. Important, and [00:23:00] I always emphasize this with patients, that the risk of an invasive recurrence at that time is half of this. When we put these numbers into context, I think of A-D-C-I-S recurrence as a nuisance, right? It's something that the patient has to go through and treat, but it is not life-threatening. So here we're talking about risk of invasive recurrence at 10 years that are single digit numbers with either no additional therapy or the addition of adjuvant radiation. And I think that that is helpful to consider because. There are downsides to radiation, right? We talked about kind of the practical things, but there's also risks and side effects that the patient occurs. And you know, some common side effects of radiation are cosmetic. You can get hyperpigmentation to the breast, you can get fibrosis and swelling, and so the breast may look different after treatment. There are also rare but serious side effects of radiation, very low risk of cardiopulmonary disease, and specifically high risk patients, and a very low risk of development of an [00:24:00] angiosarcoma within the treated field. And so here I think it's really important that we take all of this into. Consideration when we're treating a non-life threatening disease that has a rare but real potential for a serious malignancy as a consequence. And so it's really balancing pros and cons of both the benefit of the treatment that's associated with absolute risk, the patient's tolerance of risk, and the potential side effects of the treatment that we are recommending. Thank you for that. I also wanna iterate that adjuvant radiation is one of the two options available for our patient in terms of adjuvant therapy. There's also endocrine therapy, which is offered to hormone receptor positive DCIS patients. Dr. Poluski, could you talk about how endocrine therapy could further risk reduce for our patient, the risk of recurrence and also reduce risk of a new incidence of invasive breast cancer? So, endocrine therapy is considered. Specifically for patients who have hormone receptor positive [00:25:00] disease which as we mentioned is the majority of DCIS cases upwards of 75%, and this is often considered. Prevention, thinking about the development of a recurrence or a new cancer, specifically a contralateral breast cancer. Obviously radiation is treating the index breast alone, but endocrine therapy does have the benefit of protecting both sides. And I think about the risk reduction here from the randomized trials that assessed the benefit of endocrine therapy of about a 30% risk reduction. So it is an additive benefit. But a little bit less in terms of the absolute index breast risk reduction compared to radiation therapy. And this is another situation where we're balancing risks and benefits. So we have added benefit for both recurrence and contralateral breast cancer development. Side effects are real, and we see this for our patients with invasive breast cancer, where this is routinely recommended. Again, because in that situation, there's a survival benefit. No survival benefit with the addition of endocrine therapy for DCIS. And so when we [00:26:00] think about what that looks like for women who take Tamoxifen and Tamoxifen can be used in both pre and postmenopausal women, the standard treatment here is 20 milligrams daily for five years. Common side effects are menopausal symptoms. Tamoxifen is a selective estrogen receptor modulator. Hot flashes are the most frequent reported side effect as well as vaginal dryness. Mood changes with this, and then we think about the serious but rare side effects of about a 1% risk of blood clots and a 1% risk of uterine hyperplasia or. Uterine cancer, in particular in postmenopausal women. When we look at aromatase inhibitors, which are appropriate for postmenopausal patients, there's a different side effect profile. Common side effects are muscle and joint aches and pains, arthritic like symptoms, and you can also get bone loss and progression of osteopenia or osteoporosis. That is all being balanced when we're thinking about that. 30% risk reduction in this context. There is another potential [00:27:00] option here, which is the use of low dose tamoxifen. A few years ago there was a randomized trial out of Italy that randomized high risk women, including those with ER-positive DCIS. To five milligrams of Tamoxifen for three years. So a lower dose with a shorter course and found a 50% risk reduction in breast cancer events compared to placebo. And so this looks to be another exciting option, and the benefit here is that the side effect profile was much more tolerable. This appears to be a, an easier. Treatment for women to take with the caveat that current data supports that most of the benefit here is in postmenopausal women. So it is unclear which premenopausal women may benefit from low dose tamoxifen. But when we think about uptake, when we're weighing the pros and cons here nationally, it's about a third of patients with DCIS who elect to go on to endocrine therapy for risk reduction. I think it's important to just summarize a few quick [00:28:00] hits here. Surgery is the current first line Treatment for D-C-I-S-A two millimeter margin is optimal to minimize recurrence risk and will be tested on your ward exams. Endocrine therapy is nationally only uptaken by a third of our DCIS patients, which was a fact that actually surprised me, but it is a risk reducing option for hormone receptor positive DCIS patients. Before we pivot, I just wanted to point out something that we didn't really cover, which is for those patients who either require or elect a mastectomy for DCIS, they typically do not receive any adjuvant therapy. So no radiation, no endocrine therapy, and the risk of recurrence after mastectomy for DCIS is about one to 1.5% in women who are. Over 40 and, and maybe up to 4% in women under 40. That's really just based on a single institution study. Unlike invasive cancer, we don't have a head-to-head comparison of lumpectomy and radiation versus mastectomy [00:29:00] for DCIS, however, from the retrospective data we have, it appears to be a really highly effective treatment. Not that that would. Necessarily make us recommend it, but for women who do need to have it, they can be assured that surgery alone is excellent local control. That's a good point, Stephanie. Agree with adding that. You know, if we compare rates of local recurrence for patients who undergo mastectomy, I typically say about a 2% risk of invasive recurrence post mastectomy for DCIS. And importantly, if you utilize the M ms KCC mammogram, for most patients who complete a lumpectomy by adding. Radiation and or radiation plus endocrine therapy, they get to an invasive risk recurrence that matches that. So there are ways to get to very similar invasive risk profiles with. Kind of very different treatment algorithms, situations. DCIS can be challenging because patients have different risk preferences and clinical [00:30:00] presentations like Dr. Poluski iterated, there are different treatment regimens or algorithms that can be tailored for the patient preferences and get to the same answer of risk reduction in different ways and different strategies. There is growing concern that we are overtreating certain individuals. Particularly those with low risk features in DCIS, we now have several clinical trials addressing deescalation of care in DCIS. So studies that are looking at whether some women can be safely monitored without immediate surgery, let's focus on some ex. Citing new data from the COMET trial. So the COMET trial is the comparing an operation to monitoring with or without endocrine therapy for low risk DCIS. Their two year results were published in December of 2024. This trial compared active monitoring, which in this case included surveillance, diagnostic mammograms every six months for the affected breast, and every 12 months for the unaffected. [00:31:00] Breast patients in the surveillance cohort also had the option of being on endocrine therapy. This active monitoring cohort was compared to the guideline concordant care cohort, and in that cohort, the patients underwent surgery plus or minus radiation, plus endocrine therapy as adjuvant options. And this was specifically looking at. Low or intermediate grade DCIS patients. So the cohort overall was roughly a thousand women, aged 40 and above with a new diagnosis of low or intermediate grade hormone receptor positive DCIS. And they were randomized to either active monitoring or surgery. The key finding from the two year results is they were looking at the cumulative incidents. Of invasive breast cancer in both cohorts as the outcome. The two year rates of invasive cancer were similar between both groups, roughly at 4.2% for the active monitoring cohort, and roughly 6% in the [00:32:00] surgical cohort. And the total results suggest that active monitoring is not inferior to having surgery and subsequent adjuvant therapy in select patients with low risk hormone receptor positive DCIS. I wanna discuss this with our attending experts here, Dr. Poluski. What's important to recognize about how the rates of invasive breast cancer compare between the monitoring cohort and the surgery cohort? Thanks. I think that, just putting this in context for the guideline, concordant care, the invasive cancers here were likely all or nearly all diagnosed at the time of surgical excision. So these were upgrades. If you look at the Kaplan-Meier curves and the trial, that curve goes up immediately. Whereas in the active surveillance cohort, that 4% of cancer diagnoses is a slow incline in the curve of diagnoses. Unsu, subsequent. Screening tests that reveal the change. So, couple important [00:33:00] things here. I mean, those numbers sound quite low. This is two year follow up. But the other important caveat here is that this is a unique population of highly motivated individuals who were really, I think, interested in deescalated care and avoidance of surgery. A pretty striking number is that almost half of the women. Randomized to guideline concordant care with surgery, did not undergo surgery. And so that really kind of muddies these numbers here. If you look at the actual treatment that patients received, if you take the women who did have surgery that invasive cancer rate, and that group was about 9%, so a little bit higher. So still suggesting that this is a. Pretty selected low risk group because we know in other studies when low risk patients are identified, the upgrade rates are still upwards of about 20% in clinical practice, so identified as a pretty low risk group of individuals [00:34:00] motivated not to have surgical care. On the flip side, in the active monitoring, I think of this more as a non-surgical arm because 70% of these women were on endocrine therapy, so they were getting treated for DCIS, just non-surgical treatment. So that really raises the question of. Preference in practice. Lots of patients don't stay on endocrine therapy, and so we're weighing, you know, the potential morbidity and tolerance of surgery versus the willingness to stay on a long-term medical therapy. So I think all of that is really important to take into context as we think about these early. And the key here is early results. Like Dr. Poluski is saying, the common trials, initial published results are just at the two year time point. They have planned results that will result in five, seven, and 10 year time points as well. Dr. Down scanner, what do you think that the longer term data might reveal? And I know this is a difficult question, but I'm just curious. Do you foresee differences emerging at the longer follow-up [00:35:00] periods? I think one of the major criticisms of this study thus far is the short follow up for a disease that we know has a long natural history, particularly ER positive DCIS and ER positive invasive breast cancer. So when we were looking at the nomogram before, we were looking at five and 10 year risks of recurrence. We weren't looking at one in two year risks of recurrence, and that's because these recurrences can happen 5, 10, 15, 20, even 30 years later. And so I think that. We will probably see some differences as time goes on, but again, it's difficult to truly know what the differences are when there has been so much crossover and we're really comparing almost like primary endocrine therapy to surgery. Thank you both. Casei is supposed to highlight some of the more nuanced approaches and practice it. Our second patient is a 65-year-old woman who presents with a newly diagnosed hormone receptor positive low grade DCIS [00:36:00] of the left breast after a core needle biopsy. She's hesitant about proceeding with surgery after you discuss treatment options with her. And I just wanna set the stage by saying importantly, active surveillance alone is not. The current standard of care. This is just to illustrate some of the more difficult conversations you might be having in clinic. So, Dr. Poluski, how would you discuss treatment options with this patient and maybe even talk about endocrine therapy with this patient? I think that we've all had patients who meet these criteria in clinic. You know, we're seeing a lot of personal decision making in this process of patients coming in on both ends of the spectrum of wanting really aggressive everything for treatment. And some patients who really are concerned about overtreatment. So here I do emphasize that potential initial upgrade risk, that there could be an invasive cancer there right now that we don't know about. And that, to me, I think that that's important information to understand, to impact treatment recommendations. But for somebody who says, I'm really not interested in surgery for [00:37:00] this. Pre-invasive lesion. Things I'm thinking about, number one are, have we adequately sampled the findings? So how big is this lesion in common? If the area of calcifications was greater than four centimeters, they required multi-site biopsies. Is there any concern of a mass component or something that would increase that If we feel like she's been adequately sampled and has a small area of screen detected, low grade ER positive DCIS and strongly. Is interested in non-surgical management. Then these are patients that I do review the short-term comma data, what we know, what the limitations are and the potential important aspect of endocrine therapy here. And so I do refer them to medical oncology for consultation, for discussion of adjuvant endocrine therapy, and I follow them closely. So they come back every six months for a mammogram and physical exam with the understanding that we're really looking for changes in progression and that would warrant additional workup and treatment at that time. Thanks, Dr. Palki. Dr. Don Skinner. One of the intriguing aspects of the COMET trial was [00:38:00] the significant non-compliance. So 44% of the patients assigned to the surgery arm declined it, and 14% of the patients originally assigned to the active monitoring cohort also declined active monitoring in lieu of surgery. So did these findings surprise you? These findings don't surprise me. I think especially the study itself attracted. A particular set of patients, as Dr. Polski mentioned earlier, who were interested in deescalating. And so I think there were probably a certain percentage of patients who were disappointed with the arm of the trial. They were randomized to. They probably would have opted for deescalation. Outside of the trial if the trial didn't exist. And this, you know, gave them an opportunity to participate in a trial, which is amazing for patients who are able to do that. But, so, no, absolutely not surprised. One thing I think that. Came to mind when Dr. Pki was talking about [00:39:00] potential active surveillance with or without endocrine therapy is this concept that a lot of patients are not compliant with endocrine therapy. And we know this from women who are older with invasive cancer who emit radiation. It's very difficult for them to comply with endocrine therapy, and those studies were really. Shown to be safe in women who complied with five years of endocrine therapy. So I think there's ongoing work looking at can we give women a trial of endocrine therapy and see if they're going to be compliant and then decide what to do. Patients know more and more and they want more and more input into their care. But in the end, we are being asked for our opinion. And so, you know, we have to be honest with them about what the data shows and what is the safest thing for them but also be willing to work within the boundaries of what's acceptable to them. I think one thing that's really important to remember after this entire discussion is that. A [00:40:00] lumpectomy is a pretty low risk procedure, can usually be done with sedation and local anesthetic, or maybe even just local anesthetic alone. The risks are quite low, and a lumpectomy alone is a great option to treat DCIS. So just remember that surgery is still really relevant and a lumpectomy by itself might be much more tolerable than, for example, five years of endocrine therapy. I think that's a great summary of our overall discussion as well, especially with DCIS and breast disease. I think there's a lot of incredible data and emerging data that has to be integrated also with a shared decision making model, which is why this can be a clinical challenge. But hopefully our discussion today will help real world practitioners in their clinical practice. So that wraps up our deep dive. Thank you so much to our incredible guests, Dr. Poluski and Dr. Down scanner for sharing your insights. See you in our next episode on the Breast Specialty Series. Thanks for listening to Behind The Knife, go Forth and [00:41:00] dominate the Day.