Welcome back to An Introduction to Breast Cancer. I'm Dr. Anees Chagpar. So in previous lectures we've talked a little bit about breast cancer, what it is, different types. We've even talked about surgical management of breast cancer in terms of removing the cancer from the breast. Today we're going to talk about lymph node evaluation. So you remember when we started talking about surgical management? We said that there were two main objectives. The first objective was to remove the cancer from the breast. But the second objective was to evaluate lymph nodes. Why evaluate lymph nodes? Well, there's two main reasons, staging and local control. Staging you remember we talked about. If cancer is going to spread anywhere, it often spreads to the lymph nodes first, and that's an important part of that staging criteria that we talked about. It's the N in TNM. Local control simply means that if there's cancer in lymph nodes, we want to remove that, because ultimately our goal is to make patients cancer free. So one question that you might ask is, but what about survival? Does removing lymph nodes improve a patient's life? And the answer is no. So here's data from the NSABP B-04 trial. This was a clinical trial that randomized patients to either have a radical mastectomy, which was standard of care back in the day, where the breast would be removed, the pectoral muscles would be removed, and all of the lymph nodes. Or to simply have the breast removed, without taking any lymph nodes. If you look at these graphs, you can see that certainly patients who have positive lymph nodes do worse than patients who have negative lymph nodes. That's why that line is below the one that is node negative. But if you look at the different surgical techniques, the dotted line versus the solid line, again, they're superimposable. So removing lymph nodes doesn't save lives, but it does help us to understand a patient's prognosis, which is really important in terms of how we treat them. So for generations, the way that we would evaluate lymph nodes was with what we call an axillary lymph node dissection. That's where we would remove all of the lymph nodes in the armpit. Now that's a fine procedure. It certainly will give us information about how many lymph nodes are involved. And if any are involved, we'll certainly get local control. So it meets our two objectives. But it has a lot of morbidity. So patients can get numbness, often in this upper, inner aspect of their arm, due to a severing of what's called the intercostobrachial nerve. That's a nerve that goes from your chest to the upper aspect of your arm. Patients can also get swelling. Many patients worry about something called lymphedema. And while this is very scary for a number of patients, for most, it's just that your rings don't fit. The other thing is that patients can get decreased range of motion of their shoulder, so they'd need to do exercises to make sure that they don't get a frozen shoulder. But boy, wouldn't it be great if we could avoid the morbidity of taking out all of these lymph nodes, especially if patients didn't have cancer in their lymph nodes? When we talked about screening, way back when, we talked about mammography and finding cancers before we could ever feel them. Well, these days, the majority of patients present with lymph node negative disease. That is to say that the cancer hasn't spread to the lymph node. We're finding it really early. So why should we take out all of these lymph nodes and cause all of this morbidity if lymph nodes are negative? We needed a better way to stage patients. Enter sentinel lymph node biopsy. This has now become standard of care. How does this work? Well, we inject a radioactive tracer, or a blue dye, into the breast, and that will travel to the first draining lymph nodes, or what we call the sentinel lymph nodes. Those are the lymph nodes that if cancer was going to go anywhere, it would go to those lymph nodes first. We can identify those lymph nodes right in the operating room, either using a handheld gamma probe or looking for the blue dye. And when we find that blue node that's radioactive, we can take that out and send it to our pathologist. Sometimes our pathologist can look at it right under the microscope right then and there, and can tell us whether there's cancer there or not. You can see in this picture, this is a slice of a lymph node, and this little deposit right here, well, that's cancer in that lymph node. So we can get information about whether there's cancer in the lymph nodes or not, and then only do an axillary lymph node dissection if there's cancer there. But first we needed to know whether this technique actually worked. Can we find the sentinel lymph node? And when we find it and the pathologist says it's negative, does that really reflect all of the other lymph nodes in the armpit? Well, there have been a number of studies that have looked at that question. So here are some trials where that was exactly what was done. Surgeons would do a sentinel lymph node biopsy, but they would also take out all of the remaining lymph nodes, because that was standard of care at the day. What we found by doing this was that the accuracy was very high and that we could often find the sentinel lymph node. And for the most part, if the sentinel lymph node was negative, that is to say, the pathologist said there's no cancer there, then there wouldn't be cancer in the remaining lymph nodes. So we became very comfortable with the idea that we only need to take out the remaining lymph nodes if that first draining lymph node had cancer. Now for a lot of this lecture and for a lot of this course, we've talked about clinical trials and the fact that clinical trials really are what move the field forward. So was there ever a randomized control trial that really showed us that we can do this? The answer is yeah. The NSABP B-32 was a trial that randomized patients. Half the people had an axillary node dissection no matter, what because that was standard of care. Half the people had a sentinel node biopsy and only an axillary node dissection if that sentinel node was positive. And as you might guess, the survival rates were equal. Well, that should come as no surprise to you. Remember back to the NSABP B-04? We knew that there wasn't going to be a survival difference, because removing lymph nodes doesn't improve survival. But here's the interesting part. Look at the lymph node recurrences. They were roughly the same in the two groups. That reflects the fact that if the sentinel lymph node was negative, it truly was negative for the vast majority of patients. And we knew that looking at the previous studies that I showed you. So it's because of those studies and this trial that sentinel lymph node biopsy has really become the mainstay of lymph node evaluation for patients with breast cancer. So how does this work? We do a sentinel lymph node biopsy, and here are some pictures showing you what cancer looks like. And we define a positive sentinel lymph node as a tumor deposit that's more than 0.2 millimeters. That's pretty small. Now, there are things called micrometastases, which are 0.2-2mm, or macrometastases that are more than 2mm. All of those are considered lymph node positive. So if you go back to that staging scheme that we talked about, those would be N1 disease. You can have cancer cells in a lymph node and still be lymph node negative, if you have what's called isolated tumor cells. Isolated tumor cells are tumor deposits less than 0.2mm. These are stray cells that just happen to have been in a lymph node, but really there's unknown clinical significance. And so these patients are considered node negative. Historically what we did is if patients had a sentinel lymph node that was positive, we would complete an axillary node dissection. And if they were sentinel node negative, great. They could be spared that lymph node morbidity associated with taking out all of the lymph nodes. But a lot of patients, the sentinel lymph node is the only lymph node that has cancer. So then is there a way to predict which patients might have other lymph nodes that are involved? Because truthfully, if the only disease is in the sentinel lymph node, then taking out the remaining lymph nodes really does no good. The majority of patients really don't have a lot of disease in non-sentinel lymph nodes. So a number of clinical trials have asked the question whether we really need to finish an axillary lymph node dissection for every single patient who has a sentinel lymph node that's positive. Remember back to the lecture that we talked about where we looked at breast conserving surgery, or partial mastectomy, versus total mastectomy? The local recurrence rates, remember, were different, because we were leaving a lot of breast tissue behind when we did a partial mastectomy. So what did we do? Do you remember how we reduced the local recurrence rate? We added radiation. Well, when we talk about radiation, you'll find out that radiation is often given in what's called tangential fields. So you have one tangent that comes this way, one tangent that comes this way, and ultimately what happens is you're covering the armpit where the lymph nodes are. Hm, maybe radiation is all you need to cover non-sentinel lymph nodes. So how might we answer that question? With a clinical trial, of course, and there have been a number of them. So here I list a few of them. I'm only going to talk about one of them, in the interest of time. This is the ACOSOG Z-0011 trial. This was a trial that took women who presented with a positive sentinel lymph node and randomized them to standard of care, which was to finish the axillary node dissection, or to simply have radiation. And that radiation was in the tangent fields that they would get anyways, because all of these patients had a partial mastectomy with whole breast radiation therapy. And as you can see, overall survival rates were equal. Not a surprise. We know that removing lymph nodes doesn't improve survival. But the local recurrence rates, particularly in the lymph nodes, was really small in both groups. So with a median follow-up of over six years, the local recurrence rate was still under 2% in the lymph nodes, even when you didn't complete an axillary lymph node dissection. Now any time you try to apply clinical trial data to your practice, it's important that you keep in mind which were the patients who were included in the trial. The Z-0011 trial only included people who had tumors less than 5 cm. They only could have one to two positive nodes, so patients who have three or four or five positive sentinel lymph nodes were not included in this trial. They could not have neoadjuvant chemotherapy, so chemotherapy prior to surgery. And all of them had a partial mastectomy with whole breast radiation. So what does this mean? If you have a big cancer, or you're having a mastectomy, or you're not having whole breast radiation, or you've had chemotherapy before your surgery, or you have three or more positive lymph nodes, then these trial data don't apply to you, and you'd still need an axillary lymph node dissection. The majority of these patients had relatively small cancers. And the vast majority were treated with systemic therapy, either chemotherapy or hormonal therapy. Now truthfully, that's what the majority of patients these days who are treated in industrialized countries have cancer that looks like. So they often will have small cancers that are treated with adjuvant therapy. So as time goes on, more and more patients are requiring less and less surgery. Less and less surgery in the breast, less and less surgery in the axilla, which means less and less morbidity, which is a great thing for our patients. Next time we're going to talk about some of the complications, particularly about lymphedema, which is one that every patient worries about, what you can and cannot do. And we're going to answer some of their most commonly asked questions. I hope you'll join me. Until next time, I'm Dr. Anees Chagpar.
