The Sentinel Lymph Node and Breast Cancer Spread
A cautionary report published in the December issue of the journal Cancer has determined that prior chemotherapy can lead to a high false-negative rate when looking at the sentinel lymph node to detect breast cancer spread.
A "sentinel node" is the first lymph node to which a tumor drains, and therefore is the first place to which cancer is likely to spread. (In some cases, it appears there can be more than one sentinel node.) In breast cancer, the sentinel node is usually located in the axillary nodes, the group of lymph nodes under the arm.
Dr. Benjamin Anderson and colleagues from the University of Washington evaluated 15 patients who had undergone prior chemotherapy before their sentinel node dissection. They found an "unacceptably high" false-negative rate when prior chemotherapy was involved. "A negative sentinel lymph node dissection is only slightly better than chance at predicting negative axillary lymph nodes among [chemotherapy-treated] patients," they wrote.
The researchers blamed the high false-negative rate on lymphatic channels becoming distorted after chemotherapy shrank the primary tumor, the uneven effect of the chemotherapy, or multiple drainage sites from an originally large tumor.
In spite of these findings, a growing body of research is concluding that the sentinel node can be used to accurately determine if cancer cells have spread beyond the tumor to the lymph nodes. In a sentinel node biopsy, only one or a few lymph nodes are removed for laboratory analysis when a patient has a lumpectomy or mastectomy. Preliminary studies suggest that if lab tests find no cancer cells in the sentinel node, the patient is much less likely to have tumor cells in the remaining axillary nodes.
In fact, tracking the spread of breast cancer through the sentinel node has become one of the most promising diagnostic strategies for breast cancer patients. "When performed by a competent surgeon," says Dr. Lorraine Tafra, director of the breast center at the Anne Arundel Medical Center in Annapolis, Md., "the sentinel node can be identified more than 90 percent of the time. If the node is identified and dissected and found to be cancer-free by a pathologist, further surgery to dissect the rest of the lymph nodes can be avoided."
This is important because removing fewer lymph nodes can mean significantly fewer adverse side effects.
In a study published in the journal Cancer, Dr. Peter Schrenk and colleagues from the Ludwig Boltzmann Institute for Surgical Laparoscopy in Linz, Austria, compared 35 women who underwent sentinel lymph node biopsy with 35 women who underwent complete axillary lymph node dissection. They noted that arm stiffness and strength did not differ between the two groups. And neither surgery significantly affected the patients' activities of daily living.
However, they found that patients who had axillary lymph node dissections had more post-surgical complications than those who just had sentinel node biopsies. These complications included swelling of the upper arm and forearm, pain, numbness, motion restriction, and a significantly higher rate of lymphedema. An Overview
In the late 1970s, researchers began looking for a better way to test for the spread of cancer from tumors. The question was asked if there was a single node-a sentinel node-that would be the first lymph node to be affected by spreading cancer cells.
Interestingly, the concept of mapping the sentinel node was first reported in 1977 by a researcher studying cancer of the penis. The technique was later used to study drainage patterns of melanoma, and was first reported for breast cancer in 1993. Since then, researchers have improved methods for finding the sentinel node, and a growing number of studies are showing that when the sentinel node is "negative" (free of cancer), the remaining lymph nodes are also cancer free in a majority of cases.
There are currently two standard methods for finding the sentinel node. One is to inject a blue dye near the breast tumor and track its path through the lymph nodes. The dye accumulates in the sentinel node. In a similar technique, doctors inject a safe, small amount of a radioactive solution near the tumor and then use a gamma detector to find the "hotspot," or the node in which the solution has accumulated.
Sentinel lymph node dissection has become so promising that the National Cancer Institute has just announced a pair of major clinical trials to compare the value of checking just the sentinel node for cancer spread versus the historic standard of removing a large number of lymph nodes.
"Although sentinel node biopsy has attracted widespread attention by surgeons and patients alike, the procedure has not been compared to the time-tested standard of complete axillary dissection in a clinical trial designed to assess cancer recurrences and overall survival," said Dr. Jeffrey Abrams of NCI's Division of Cancer Treatment and Diagnosis.
The recent annual Miami Breast Cancer Conference in March highlighted a trio of additional clinical trials that are examining the effectiveness of sentinel lymph node dissection in women with breast cancer.
One trial, dubbed Z0010, is examining how a breast cancer patient's prognosis differs if microscopic breast cancer cells (micrometastases) are found in the sentinel nodes and bone marrow, but not in the axillary lymph nodes.
A second trial, Z0011, is comparing axillary lymph node dissection with sentinel lymph node dissection in women with node-positive cancers (cancers in their lymph nodes). The researchers want to determine if axillary lymph node dissection is still a beneficial diagnostic tool.
In another presentation at the conference, Dr. Patrick Borgen, from the Memorial Sloan-Kettering Cancer Center in New York City, reported on a study evaluating 1,800 cases of lymphatic mapping for breast cancer. His group identified a median of two sentinel lymph nodes per patient, and the cancer was found in the second or third sentinel node 25 percent of the time. Borgen said his team's findings suggest that searching for additional sentinel nodes may be important for accurately determining the spread of the disease.
Borgen's success rate for identifying the spread of breast cancer via the sentinel node now ranges from 94 to 96 percent. He said this rate would probably be even higher except for some technical errors and variations in lymphatic flow. And Borgen's impressive results are typical of those from a growing number of studies focusing on the sentinel node.
Without question, as Borgen suggested during his presentation, the hypothesis that there is a sentinel lymph node (or nodes) most likely to be the first site(s) of breast cancer spread is a valid one. And because of the technique's remarkable success, other researchers involved with different cancers are now turning their attention toward the sentinel node.
Cancer, December 2000; 89:2187-2194
Department of Defense Breast Cancer Research Program Meeting, June 10, 2000, Atlanta, Georgia
The National Cancer Institute (www.nci.nih.gov)
Cancer, February, 2000; 88:608-614
Cancer, March, 2000; 88:1099-1107
The 17th Annual Miami Breast Cancer Conference, March 3, 2000
Journal of the American College of Surgeons, 1999; 189:539-545
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