Anna Coppinger, 61, a school cafeteria worker from Hingham, lies waiting outside the operating room at South Shore Hospital in Weymouth, chatting with her husband and daughters – and wincing whenever she jostled the needle that had been placed in her left breast several hours earlier to guide surgeons to the exact spot where her tumor lay.
As she liese there, a radioactive substance called technetium-99m sulfur colloid, injected earlier, is seeping through the lymph ducts in her breast toward lymph nodes in her armpit.
Like a growing number of people with cancer, Coppinger was about to undergo a relatively new – and still-controversial – procedure called sentinel node biopsy.
Instead of removing 10 to 20 lymph nodes in the armpit to check for signs of cancer, Coppinger’s surgeon, Dr. Suniti Nimbkar, is planning to remove just the first, or “sentinel,” node into which cancer cells were most likely to have spread. If that node turns out to contain cancer, Coppinger will have another operation to remove the rest of her armpit lymph nodes. But if it’s clean, she’ll get no further node surgery.
Ever since doctors began experimenting with sentinel node surgery in melanoma patients a decade ago, the technique has “caught on like wildfire with most surgical oncologists,” says Dr. Kenneth Tanabe, chief of surgical oncology at Massachusetts General Hospital.
Today, this state-of-the-art technique is well-accepted for melanoma, and is being studied for a number of other malignancies, including colon cancer. But perhaps its most controversial application is in women with breast cancer. The National Cancer Institute insists the procedure should be considered “investigational” until the results of two major studies, now underway, are available.
But around the country, surgeons like Nimbkar are already switching to the new procedure, convinced that there is no need to wait.
The argument in favor is clearcut. Many solid tumors have been shown to “drain,” or shed cancer cells, in an organized pattern, first to the nearest lymphatic ducts and nodes, then to more distant ones, although cancers sometimes “skip” directly to distant ones. (The lymphatic system is part of the body’s immune defense system. Cancer can also spread directly through blood vessels.)
This means that taking out only the sentinel node could be just as reliable a way to tell if cancer has spread as more drastic node surgery. Indeed, two reviews published in 1999 and 2000 suggest that in breast cancer patients, if the sentinel is negative, the other armpit nodes will also be negative 95 percent of the time. If the sentinel node is positive, there’s a 25 to 50 percent chance that the other armpit nodes will be positive.
Sentinel node biopsy clearly causes less pain. And it avoids many of the complications of the full nodal surgery, which more than 80 percent of women suffer. These range from temporary discomfort to numbness, persistent burning sensations, infections, limited shoulder mobility and more rarely, lymphedema, in which the arm can become chronically swollen and prone to infection.
But a key question looms: Does taking out all the armpit lymph nodes make a difference in long-term survival, or is the outcome be the same if only the sentinel nodes are removed?
Historically, one of the main reasons that surgeons removed all the lymph nodes in the armpit of a woman with breast cancer was to get rid of any possible traces of cancer, says Dr. David Krag, the lead researcher for NCI’s study in Vermont and professor of surgery at the University of Vermont Cancer Center in Burlington.
But a government-sponsored study nearly 20 years ago began to challenge that notion. It looked at women with breast cancer who had all their armpit nodes removed and those who didn’t and could not find any “survival difference,” says Dr. Jeffrey Abrams, senior investigator in the division of cancer treatment and diagnosis at the NCI.
Indeed, “there is no firm evidence that removing involved lymph nodes improves survival, even though it is standard practice,” the NCI notes on its website (http://cancer.gov) “Randomized studies suggest that lymph node removal may not improve survival, although it is valuable in determining the stage of the cancer. Sentinel node biopsy can be used to determine stage, so that may be all that is necessary, even in node-positive women.”
On the other hand, the 20-year old American study that showed no survival difference did not have enough patients to detect differences of less than 10 percent in survival. Moreover, when data from this American study are lumped together with data from five studies from outside the US, the overall picture suggests that women who have full lymph node dissection do have a five percent survival advantage over those who don’t.
In other words, leaving cancerous nodes in the body does appear to be “dangerous for survival,” Krag says.
In Krag’s own study, 5,400 women will be randomized to get sentinel node biopsy plus a full armpit node dissection, or to sentinel node biopsy only. Those who get the full dissection then go on to get whatever subsequent treatment – chemotherapy or radiation – doctors deem best.
Among those who get only sentinel node biopsy, if there is no sign of spreading cancer, there is no further no surgery, although, like the first group, they get whatever chemotherapy or radiation they need. If there are signs of spreading cancer, those women get a full armpit node dissection, as well as appropriate further therapy.
“Until you prove the ultimate survival is the same, you haven’t proved that sentinel node biopsy can replace complete removal of all the underarm lymph nodes,” says Abrams of NCI.
Krag’s study will also try to determine whether full armpit node dissection decreases the odds of recurrence of cancer in the armpit, and will compare the value of sentinel node biopsy versus full dissection as a way of staging patients, or classifying them into categories to determine their subsequent treatment.
The other major study is being led by Dr. Armando Giuliano, chief of surgical oncology at the John Wayne Cancer Institute in Santa Monica, CA.
In his study, which is designed to include 7,600 women with breast cancer, Giuliano’s team will give all the women a sentinel node biopsy. Women with negative sentinel nodes will receive whatever further therapy doctors think best.
Women with positive sentinel nodes – expected to number about 1900 – will then be randomized to full armpit node dissection or no further node surgery or radiation. The idea is to see whether there is any therapeutic value to removing all the lymph nodes. But the prospect of leaving cancerous nodes in place is proving a tough sell, Giuliano says, because many women do not want to take a chance on leaving lymph nodes in if there are any signs of cancer.
Both Giuliano and Krag will also use a new test to try to determine whether women whose sentinel nodes are negative may nonetheless have “micrometastases”- tiny traces of usually-undetectable cancer.
Normally, scientists examine lymph nodes with a simple test dubbed “H&E,” for hematoxylin and eosin, colored stains that make all cells visible and allow pathologists to see which cells might be cancerous.
The new technique uses IHC, or immunohistochemistry, which involves antibodies that stain only epithelial cells. A healthy lymph node usually contains no epithelial cells. But cancer cells are epithelial cells, so a node that contains even a few cancerous cells will stain positive. The IHC technique, only done currently if there is ambiguity on the H and E test, can detect even one or two cancer cells.
At South Shore Hospital, Coppinger’s sentinel lymph node surgery takes less than an hour.
With Coppinger under general anesthesia, Nimbkar slips a sterile covering over a special wand hooked to a geiger counter on a table.
By now, the radioactive substance (technitium sulfur colloid) that was injected into Coppinger’s breast earlier has migrated to her lymph nodes. Sure enough, as Nimbkar slides the wand over Coppinger’s armpit, the geiger counter squawks as Nimbkar finds a “hot spot.”
“This is just what you hope for,” says Nimbkar, as she makes a 1-inch incision just above the hot spot. Slowly, she dissects away the top layers of fat, probing with her finger until she locates the first node. Carefully, Nimbkar cuts out the node, then slips the wand back into Coppinger’s armpit. The geiger counter now registers almost nothing, a strong sign that there are no other nodes in the area.
“I think we’re good,” she says, beginning to sew up the small armpit incision before moving on to do a lumpectomy to remove the tumor in Coppinger’s breast.
A week later, Coppinger says she’s “doing terrific – I’m going to play baseball.”
Her lab results turned out fine, too. Her node was negative, which means it’s very unlikely that cancer has spread to any other nodes.