We’re here at the BGICC, a very important conference in Egypt, in Cairo, discussing various aspects of breast cancer diagnosis, treatment. I gave two lectures yesterday on the management of the axilla. The management of the axilla for patients with early stage breast cancer has undergone significant revolution in the past 25 years. Up until the turn of the century we used to do axillary lymph node dissection electively to assess the axilla for many years, over a hundred years, based on old studies by William Halsted, radical mastectomy. Then randomised clinical trials in the ‘70s demonstrated that electively removing all the axillary nodes does not improve survival. So that was a big change.

So we still were continuing to do axillary dissection then because we didn’t have any other way of dealing with the axilla. But progressively, because obviously axillary dissection also provides a very good local control of the disease in the axilla if there is microscopic disease, but eventually we realised that we don’t need as many nodes to be removed to get the information that we need to manage the patient. 

Along came the concept of sentinel lymph node biopsy which is a selective removal of a few nodes, usually about two or three, average about three. They give you the same information, it provides good local control of the axilla as well and then spares the patient the morbidity of lymphedema and other sequelae of axillary lymph node dissection.

So over the last twenty years or so there has been significant evolution in the management and applying sentinel lymph node biopsy to most of the situations that we used to do axillary lymph node dissection. So, for example, for patients with clinically node negative axilla, if their sentinel node is negative we do not do an axillary dissection. That was based on randomised clinical trials showing no difference in outcomes. Subsequently we started thinking that maybe if one or two lymph nodes are involved when the axilla was clinically negative, meaning that the surgeon did not palpate the lymph nodes, maybe we can get away without removing more than the sentinel lymph node. So a series of randomised trials, as well, took place that demonstrated very similar outcomes whether you did the sentinel lymph node biopsy, one or two sentinel lymph nodes were positive, and then did the axillary dissection on that. So that changed a lot because it decreased further the use of axillary lymph node dissection for the management of these patients. So clear evolution in sparing the patients a lot more morbidity.

Now, initially the studies were in patients treated with breast conservation where they also received radiotherapy but subsequent studies also included mastectomy patients. So we now feel comfortable that we can offer this to patients – if they have a clinical negative axilla and one or two positive lymph nodes on the sentinel lymph node biopsy we don’t perform the axillary dissection and the outcomes are the same. 

Another trial also showed that if you, instead of taking the additional non-sentinel lymph nodes out, you irradiate the axilla the outcomes were also the same. So we have the option of just not doing the axillary dissection and observing the patient with just breast radiotherapy. Also we have the option of radiating the axilla to provide good local control for patients, let’s say, that have a little bit more burden of disease.

With that, again, we diminish the use of axillary lymph node dissection. Another way that we have done that is also through the use of neoadjuvant chemotherapy. Neoadjuvant chemotherapy early in the 1980s has shown to be equivalent to adjuvant chemotherapy. So randomised trials have shown that neoadjuvant chemotherapy is as good as adjuvant chemotherapy but it had some clinical advantages. For example, you would shrink a tumour and convert a mastectomy patient to breast conservation. Eventually we realised also we could do the same thing with the axilla. If the axilla is involved and we give neoadjuvant chemotherapy and sterilise the lymph nodes, perhaps we can avoid axillary lymph node dissection. 

So we have shown again in a series of studies and clinical trials that if the axilla is clinically negative the patient gets neoadjuvant chemotherapy, you can perform the sentinel lymph node biopsy after and if the sentinel node is negative then you don’t have to dissect, the performance characteristics are very similar. So we expanded the indication even for that group of patients.

Then we pushed even further. We tried to assess whether if the patient had positive nodes before and we biopsy them, another positive, but then she gets neoadjuvant chemotherapy and now the lymph nodes are clinically negative and we perform the sentinel lymph node biopsy, then if the sentinel lymph node is negative actually we wish to eventually not perform an axillary dissection in this setting. But, of course, we had to demonstrate the safety of that and what is the false negative rate of sentinel lymph node biopsy in that setting. It turned out that the sentinel lymph node biopsy rate was a little higher but eventually by optimising the approach of the axilla in these patients, for example, by identifying the node that was biopsied before, the so-called clip node, and removing this lymph node along with the sentinel lymph node biopsy, we were able to drop the false negative rate even further to about 3% or 4%.

So this is pretty much now becoming the standard of how we manage these patients. We map the axilla, we do the same lymph node biopsy and we also localise and remove the node that was biopsied before. And we do this in a variety of ways – we can insert clips and radiofrequency chips to identify it. With that we are very accurate in finding the disease in the axilla but we spare also patients that have negative sentinel nodes after neoadjuvant chemotherapy the full axillary lymph node dissection. So that’s a further advancement in decreasing the role of axillary dissection.

As we look into the future, then the next step will be to say, well, if the patient’s node became clinically node negative after neoadjuvant chemotherapy, the sentinel node is still positive. Nowadays the standard is to remove more nodes, do an axillary dissection, but the question is do we have to and a randomised clinical trial that has been conducted assesses this exact question. So we’re waiting now in the next year or two to find out whether maybe in that setting doing more surgery may not make a difference because these patients, of course, get radiation because they still have positive nodes. So that’s the next step to even carve out another group of patients that maybe we wouldn’t do axillary lymph node dissection. 

The last thing I talked in my lectures also was if you end up having to do an axillary dissection then are there ways to decrease the morbidity, particularly lymphedema, this is the morbidity that the patients fear the most. There have been some ways now that we have developed to actually preserve some of the lymphatics in the axilla while we do an axillary dissection by identifying them through performing what we call two options: there’s axillary reverse mapping where we inject some blue dye in the arm and you see the nodes that turn blue and you attempt to preserve those nodes because these are not nodes that are draining the breast, they are nodes that are draining the arm. If you do end up taking them out you can approximate the lymphatic surgically to make them anastomose again.  That’s one approach and the other approach is the so-called LYMPHA procedure, lymphovenous bypass, where under microsurgery when you remove the lymph nodes in the axilla you previously inject dyes in the arm, stain the lymphatics from the arm and then anastomose the lymphatics to small veins in the axilla to re-establish the lymphatic circulation. This is also a promising method that I would try to use more and more now and hopefully we get more data as well to prove that in fact lymphedema is less with this approach. So, we try to minimise the morbidity for the patients whilst getting the information that we need from the axilla and that was essentially the topic of my two lectures yesterday.