Dr. Jeffrey East, Dr. Garfield Blake and Christopher Valentine

Breast cancer surgery has two distinct components. First, there is surgery on the breast itself to remove either the entire breast (mastectomy) or the cancer with a margin of normal tissue (partial mastectomy or lumpectomy). The second component involves removal of lymph nodes from the axilla or armpit on the same side (axillary lymph node dissection – ALND), to which breast cancer usually spreads first. ALND is very important if the cancer has spread to the lymph nodes because it removes involved nodes and also provides valuable information to the Oncologist to help determine which patients will benefit from chemotherapy (and radiotherapy).

The Problems With Axillary Lymph Node Dissection

ALND does not benefit patients whose cancer has not yet spread to the axillary lymph nodes. Before the introduction of sentinel node biopsy, ALL patients with breast cancer had a complete ALND performed because surgeons had no way of knowing in advance whether a patient’s lymph nodes were involved or not. This meant that a large number of patients, who did not need ALND were having it done and were therefore at risk for the side effects of ALND without standing to gain any benefit from the procedure. Side effects of ALND can significantly impair quality of life and include permanent swelling of the arm (lymphedema), chronic shoulder and axillary pain, numbness and other paraesthesiae (abnormal sensations, such as sticking pain).

The Solution

What was needed was a way for surgeons to be able to predict whether the lymph nodes in the axilla were involved by spreading breast cancer or not. If a way could be found to do this, then ALND could proceed inthose patients with lymph node spread and avoided in those without.

Diagram of breast
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What is the Sentinel Node?

Lymph is one of the body fluids which tends to accumulate in all organs and is drained back to the blood stream via a system of vessels called lymphatics. This system of lymphatic vessels is one of the favourite routes for cancer to spread from one organ to other parts of the body. Anatomists have long known that lymph from the entire breast drains to one or two lymph nodes at the lowest part of the axilla before being distributed to the many other lymph nodes. These one or two nodes through which all the lymph from the breast must pass are called sentinel nodes (the word sentinel literally means guard or gatekeeper).

Rationale for Sentinel Lymph Node Biopsy (SLNB)

Since breast cancer cells have to pass through the sentinel node to get to the other lymph nodes in the axilla, it follows that if the sentinel node is not involved by cancer, the other nodes will also be free of cancer and vice versa. Therefore, what is required is a method to enable identification of the sentinel node in breast cancer patients. If the sentinel nodes can be identified easily, they can be removed and sent off to the pathologist who can quickly determine whether or not they are involved by cancer. If the sentinel nodes are not involved, the surgeon need not remove any more lymph nodes. If the sentinel nodes are involved, then the surgeon proceeds with the complete axillary lymph node dissection.

Dr. East and Team performing breast surgery
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METHODS OF IDENTIFYING THE SENTINEL NODE

A lymphatic labelling agent is injected into the space beneath the nipple or the tissue surrounding the cancer. This agent is rapidly taken up into the lymphatic vessels and transported to the sentinel node where it is trapped. In North America, Europe and Japan the labelling agents of choice are a radioactive colloid and a blue dye named Isosulfan Blue. The former is identified in the sentinel node using a gamma camera (a device used to detect radioactivity) and the latter by the blue colour that it imparts to the sentinel node. Both labelling agents are extremely expensive and are not cost-effective in most developing countries. Methylene blue dye is a third labelling agent which has proven to be as accurate a sentinel node labelling agent as the previous two and which is much cheaper than either. For some reason which is unclear, methylene blue has not been popular in developed countries but it represents the only methodology by which surgeons in developing countries are going to be able to offer the important technique of sentinel node biopsy to all their patients with breast cancer who are candidates for the procedure.

HOW DO WE KNOW WHEN A SURGEON IS PROFICIENT AT SLNB?

The other problem with transferring the technology of SLNB to developing countries was that surgeons need to do a certain number of these procedures (the learning curve) before they can be considered competent to offer it to breast cancer patients. Most patients do not benefit from SLNB during the “learning curve” phase of a surgeon. The most authoritative guidance with respect to the length of the learning curve used to emanate from the American Society of Breast Surgeons. This body suggested that the learning curve was probably 20 cases but admitted that this recommendation was based on expert opinion and that it appeared to be much shorter for some surgeons.What was necessary was an objective method of assessing the learning curve of individual surgeons so that those who learn faster than others would be able to offer SLNB to their patients in the shortest possible time.

Forceps point to blue sentinel node
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WHAT THE UWI, MONA-WJC RESEARCH TEAM SET OUT TO DO

The goals of the research project were twofold and both were achieved. First, Dr. East and team were able to corroborate evidence that methylene blue dye is an accurate label for the sentinel node. Second, they applied a statistical method called the tabular CUSUM in the learning curve analysis of the two surgeons (Drs. East and Valentine), using identification of the SLN as the criterion of success. The tabular CUSUM is a hypothesis test which is effectively repeated for each event and which takes account of cumulative past performance. This methodology had never been previously used to prospectively analyse the learning curve for SLNB. The researchers were able to prove that the learning curve could be as short as 8 consecutive, successfully identified cases and by a method that is easily applied by surgeons without any special statistical knowledge.

Implications of Research

Breast surgeons, particularly those in developing countries, now have a roadmap for introducing SLNB programs, using methylene blue dye, for the benefit of their breast cancer patients.