WEDNESDAY, MAY 12, 1999
"Lymph Node Status: Do We Really Need To Know?"

Whether or not to do a lymph node dissection is a problem that confronts most people who are diagnosed with early stage breast cancer today. Surgeons at the Breast Care Center are currently involved in a number of clinical studies looking at the role of the lymph nodes, whether or not sentinel node is a feasible thing, and what metastasis in the lymph node means. Henry Kuerer, M.D., a surgeon at the Breast Care Center participated in the discussion.

Cancer therapy at the turn of the century was based on radical, local control. Removing every micro focus of cancer was important. Radical surgery of the time involved removal of the pectoral muscle and a lot of lymph nodes into the axilla. It was known at the time that this was a common route of the spread of cancer, and predictive of recurrence.

In the 1970's a trial was done to see if lymph node dissection was providing any therapeutic benefits. Does removal of nodes only predict what someone's risk is, or does it actually improve outcome? The study compared mastectomy with lymph node dissection to mastectomy without lymph node dissection in clinically negative (no palpable nodes) patients. There was also a third group that got radiation to the lymph nodes without dissection. Results showed no difference in survival in the three arms of the study, but did reveal some interesting things. In those that underwent dissection, 40% had lymph node involvement. In the group that did not have dissection, only about 20% recurred. So, having microscopic disease does not necessarily mean recurrence. Delayed lymph node dissection (done at the time of recurrence) showed no difference in outcome.

The paradigm for treatment in the 1970's was that adjuvant therapy (hormone and chemo) could lower the risk of recurrence. This treatment was only given to higher risk patients, those with positive nodes. Therefore it became important to know if the nodes were positive.

In the 1980's a few trials were published showing that even patients with negative nodes derive benefit from chemotherapy. This is a proportional benefit, a relative reduction. If your risk of recurrence is low, you will derive a smaller relative benefit from therapy. 30% relative reduction might reduce low risk from 10% to 7%, whereas a 30% reduction in a high risk patient might reduce the chance of 40-50% risk of recurrence to 35%. Risk should be seen as a probability.

Today, we may only need to know the lymph node status if it will change therapy. We have some new technology that will allow us to look at lymph nodes without actually doing surgery. This would eliminate the risk of lymphedema which can be anywhere from 5-15%. We are investigating other predictive markers, like HER2, but currently none have the power to replace the information we get from the lymph node. There are no primary tumor characteristics which can successfully predict nodal status to a confidence of .05%. The technology that has emerged in the last few years involves looking at the sentinel node. The field actually started with penile cancer. Surgeons found that nodes could be either on the right or left, using the dye they could track the nodes to where the tumor was. The same concept applies to breast cancer. There is now approximately an 80-90% success rate in identifying specific nodes that drain the tumor. This is done with blue dye and/or a radioactive compound that is identified with a gamma counter. When the sentinel node is negative, 90-95% of the time there is no cancer. Most recently, the skip rate in the best surgical centers (negative sentinel node, but cancer present) is down to 2-3%.

Dr. Kuerer feels that many patients do not understand the concept of surgery as excellent local control. He feels that if cancer is identified in the lymph gland, it should be removed. He understands that many patients fear the procedure because of the chance of lymphedema. 40-50% of patients come here with cancer already in their nodes by microscopic evaluation. This is trending lower over time. Currently 80% of diagnosed cancer is early stage and a little over half of these have negative nodes. Many of these cases are now mammographically detected. The great thing about the sentinel node procedure is that in these negative cases we have avoided removing nodes that don't need to be removed. We know from large population studies that the smaller a tumor is, the less likely the nodes will be positive. A .5 cm tumor has about a 20% chance of positive nodes, depending on the grade. Nothing we know currently can get this percentage risk down below 5%, but for some people even a 10% risk is enough not to have the procedure. The challenge is to educate patients on lymph nodes when they get their diagnosis, so that people can make their own decision based on their lifestyle.

Why take out palpable nodes if there will be no difference in therapy? This is very controversial. Various centers are testing this.

Is lymphedema a sign that cancer is recurring? Usually not, but very rarely, it can be. It may be possible to tell if recurrence is due to lymphedema by physical exam. There is certainly better local control with surgery, but there may be no difference in outcome if the surgery is delayed until the patient recurs in the nodes. There is a small issue of uncontrolled local recurrence in which case the nodes cannot be removed, but this is not a big problem. The problem is that we are still dealing with cancer in a monolithic manner, doing a lot of treatment on a lot of people to make a small difference. We are now starting to tailor therapy to the individual patient, mostly in the area of hormone therapy and most recently using HER2/neu. But the discriminatory power of these markers is not perfect. We have the same problem with lymph nodes, still putting the patient at risk for lymphedema by removing nodes that may not need to be removed or will not change treatment. Another thing that must be kept in mind is that lymph nodes are sensors of risk, taking them out is not in itself going to impact survival.

Why have surgery if the cancer is advanced? Patients whose tumors are found with the diagnostic tool of mammography have been shown to have less virulent cancers. There is a 30% improvement in mortality with early diagnosis and surgery (which is the intervention tool). How many nodes are usually removed in a sentinel node procedure? The sentinel node by definition is the first to light up with blue dye or radioactive counts. There is

usually one, but there can be up to three. These can be in three possible locations: internal mammary, axillary, and subclavicular. The theory is that the cancer tracks the same way that the lymph system drains. The sentinel node in theory should be the first to contain cancer cells if cancer is present. If the sentinel node is positive, then more nodes are removed. There is a 45% likelihood that additional nodes will be positive with a positive sentinel node. The false negative rate is about 12% with breast surgeons. The technique is very refined and difficult to do well, especially for a general surgeon. There is no general rule regarding the location of the sentinel node or how long it takes to track with dye or gamma probe, but the specificity will rise if both procedures are employed as the are at Mt. Zion. There is also no rule as to how many nodes should be removed if the sentinel is positive. Most collaborative groups require a minimum number of 6 to accurately stage the patient, but this could also be 7 or 8. The nodes removed are usually limited to Level I (axillary) and Level II (internal mammary), but if the Level III (subclavicular) are palpable, they too are removed. The decision on what to take is made during the surgery. It is advisable to avoid removing many of the Level III nodes because the lymphedema rate rises significantly when these nodes are removed.

Why does cancer spread to the lymph nodes? There are some cancers that do not spread to the lymph nodes. This is a hard statement to prove, and we cannot identify the characteristics with certainty, but they may include the inability to make the right proteins to breakdown the basement membrane or set up at a distant site. Grade is also a predictor of the capacity of a cancer to spread to the lymph nodes, but not a perfect predictor.It is important to understand that metastatsis to a lymph node is not the same as metastatic cancer. New trials are studying micrometastasis (microscopic cancer cells outside the breast in the lymph node or the bone marrow which portend recurrence but doesn't assure it) to see how these cells differ from normal breast cells. Metastatic cancer does not have to go through lymph nodes to spread. Presumably the cells have gone through the bloodstream or moved through the lymph system without lodging and growing in the lymph node. Involvement with the nodes does increase the likelihood of subsequent metastasis.

Is there a relationship between tumor location and lymph nodes? Tumors on the outer breast tend to go to axillary nodes. Tumors on the inner side of the breast tend to go to internal mammary nodes. It is rare to have positive Level III (highest level) axillary nodes and negative Level I and II nodes. It is not only important if you have lymph node involvement, but how many.