SABCS 2012
Effectiveness of sentinel lymph node surgery after chemotherapy in node-positive breast cancer
Dr Judy Boughey, Mayo Clinic, Rochester USA
This was a prospective phase II clinical trial trying to evaluate the role of sentinel lymph node surgery in patients who present with breast cancer that is documented to have spread to the lymph nodes at the time of their initial diagnosis and who are treated with neoadjuvant chemotherapy. Currently in breast cancer many patients who have early stage breast cancer can avoid the morbidity of having an axillary lymph node dissection where the majority of the lymph nodes are removed by having a sentinel lymph node biopsy which is a surgical procedure resecting just the first two or three draining lymph nodes underneath the arm. Then only if those lymph nodes have cancer in them, then often clearance of the rest of the axilla and axillary dissection is recommended. Currently, however, those patients that are known to have nodal involvement with their breast cancer and who receive neoadjuvant chemotherapy are recommended to have an axillary lymph node dissection.
So we set out to see whether we could reliably identify those patients who had their cancer spread to the lymph nodes but with the use of neoadjuvant chemotherapy the cancer in the lymph nodes had been treated and regressed and now the lymph nodes were negative and to see whether the sentinel lymph node technique would work in those patients. This was a prospective study that opened in the summer of 2009 and accrued 756 patients over a two year period. Patients that were enrolled in the study had to have definite diagnosis of lymph node involvement with their breast cancer, usually performed by either a fine needle aspiration or a core needle biopsy at the time of initial diagnosis. They then received chemotherapy at the discretion of their medical oncologist and after completion of their chemotherapy, at the time that they went to the operating room for their definitive breast surgery, they underwent both a sentinel lymph node procedure and then also axillary lymph node dissection to remove the remaining lymph nodes.
The study found that the sentinel lymph node surgery procedure actually identified the correct nodal status, i.e. was able to show whether the lymph nodes were positive or negative, in 91.2% of patients. 40% of people were completely node negative and this is the group that probably does not benefit from further axillary surgery. 60% of people still had disease in the lymph nodes and when we look at these patients that had residual disease the false negative rate, meaning how often the sentinel lymph node did not pick up disease that was present in the axilla was 12.6%. This was a little bit higher than our predefined endpoint for the study, however, when we looked at the patients that had residual nodal disease we were able to identify that those patients where the sentinel lymph node mapping technically had been done using dual tracer, which means the surgeon injects both blue dye and radioactive colloid to help identify the lymph node, in those cases the sentinel node false negative rate was significantly lower at only 10.8% when it was compared with those cases where only either blue dye or radioactive colloid was used. So this highlights for us that the surgical technique is very important to ensure that we’re minimising false negative findings. We also noticed that when more sentinel nodes were resected i.e. when we did a slightly more thorough evaluation of the axilla and sampled a few more lymph nodes, the false negative rate was also lower. So in those cases with three or more sentinel nodes resected, the false negative rate was as low as 9.1% which was very encouraging.
How broadly is the sentinel lymph node used?
In Europe and the States, sentinel lymph node surgery is pretty much routinely used for those patients who present with early stage breast cancer, especially when clinical examination of the axilla and possibly even ultrasound examination of the axilla doesn’t show any sign of lymph node involvement. In those patients we often anticipate or hope that they are lymph node negative and routinely sentinel lymph node is recommended for staging of those patients.
Also increasingly we’ve been using it for patients who are clinically node negative, are treated with neoadjuvant chemotherapy and then we perform the sentinel lymph node surgery after completion of neoadjuvant chemotherapy to see whether the lymph nodes are involved with breast cancer. So it’s pretty commonly used for most cases where we have no clear documentation that the lymph nodes are definitely involved. But this is the first study that is pushing the envelope to look at, OK, even if we know by ultrasound and fine needle aspiration or core needle biopsy that the lymph nodes do have disease in there, is there a role for sentinel lymph node after chemotherapy? So it’s pushing the envelope a little bit into a new category of patients where sentinel node surgery hadn’t been used.
What are the side effects?
We still have side effects associated with this surgery in the axilla but they’re significantly less. So the main side effect the patients worry about with axillary surgery is lymphedema which is arm swelling. That can occur with sentinel lymph node surgery round about 6-8% of the time whereas with an axillary lymph node dissection those rates can vary from 12-20% for lymphedema. So this definitely decreases the morbidity and side effects related with the axillary surgery.
What is the message for the patient?
Anticipation and the hope is that we can start being a little less extensive with our surgery in the axilla and in particular the goal of this trial is really to try to get us to tailor our therapy. So for those women who present with node positive breast cancer but have a great response to their chemotherapy, maybe the tumour in the breast shrinks down a lot, the area in the lymph nodes that looks concerning resolves, that maybe they could preserve some of their axillary lymph nodes and avoid the more extensive surgery.
Up until this presentation my standard recommendation has been an axillary lymph node dissection. So I’ve seen a lot more where patients have said, “Really? Do you have to be that aggressive in the axilla? What if the lymph nodes have resolved, can we do less?” So I’ve had more of those questions. It will be interesting as we go forward, I think it will be important that we discuss this data with our patients, let them know that this is the result of a new study. I think many women would like to preserve their axillary lymph nodes if they can because a lot of women are very worried about lymphedema. Additionally, most of these patients will likely be treated with adjuvant radiation therapy and so that will also help control in any cases if there was a small amount of disease remaining.
