New data support expanding the pool of women with breast cancer who are potential candidates for sentinel node biopsy (SNB), a less-invasive procedure to determine whether the disease has spread to the lymph nodes, according to interim results from an ongoing clinical trial reported at the Department of Defense Breast Cancer Research Program meeting in Orlando, Florida. The study also provides early indications that the type of test conducted on the SNB sample may enhance the accuracy of the results.

"SNB has dramatically better benefits than axillary node dissection because it is less invasive and more accurate at finding whether the tumor has spread," said Lorraine Tafra, M.D., director of the Breast Center at the Anne Arundel Medical Center in Annapolis, MD. "This and other multicenter studies have shown that the surgeon's experience with the procedure is critical. Now we're investigating the role of other factors that might widen the applicability of the technique and further improve reliability."

SNB is replacing axillary node dissection as the procedure of choice to determine whether cancer has migrated beyond the breast for recently diagnosed patients. With axillary dissection, 10-30 lymph nodes under the arm next to the affected breast are removed in a procedure that involves surgery around nerves and the nearby major vein. The rate of complications, primarily fluid collection, infection, and loss of sensation in the arm, can be as high as 25%-50%. However, only a few of these axillary lymph nodes actually drain from the breast and are appropriate first-line indicators of metastatic disease. Most women have one or two such "sentinel" nodes.

With SNB, the surgeon injects one or more agents around the tumor, which then travel through the lymphatic pipes, highlighting the lymph nodes most likely to contain metastatic disease; no major nerves or vessels are disturbed. If the sentinel node does not contain cancer cells, the chance of the disease being in the remaining lymph nodes should be very small, explained Tafra.

In this study, scientists compared biopsy results from over 1,200 patients who had SNB, the majority of whom also then had the standard axillary node dissection procedure, to see whether they could identify any patient-specific factors that might be related to a "false-negative" SNB reading -- one that misses cancer in the sentinel node but finds cancer in an axillary node.

The data showed no association between a false-negative reading and patient age, tumor type or location, multiple versus single cancer sites in the breast, or preoperative chemotherapy, thus making thousands of women eligible for SNB who were previously excluded. What initially appeared to be a higher false-negative rate for women who had had a partial mastectomy, compared with open or core biopsy, disappeared with subsequent analysis of a larger group of patients.

"The sentinel node will not accurately reflect the other lymph nodes in less than one percent of patients, and it's clear that SNB will be both more accurate and less traumatic than the axillary node procedure for the vast majority of patients," Tafra said.

Furthermore, the study is finding evidence that the technique used to analyze the SNB tissue may be an important factor in the accuracy of the results. When 36 false-negative SNB specimens from 18 patients were examined with a molecular test called RT-PCR, tumor cells were detected in 61% of these nodes. RT-PCR amplifies the signal from the tumor so that detection of metastatic cells is much more sensitive than with H&E, the standard pathology test.

Additionally, in this study, tissue for RT-PCR was sampled throughout the sentinel node. Pathologists usually are able to examine only a few central sections of each lymph node, especially with the large number of nodes from standard axillary dissection, Tafra explained.

Early data from this study reveal a statistically significant increase in disease-free survival for patients whose nodal biopsies were negative for cancer on both pathology tests, suggesting that the cancer really was confined to the breast, compared with those whose biopsies were negative with H&E but positive with the more sensitive RT-PCR test.

"Thus far we've done RT-PCR analysis for less than half the patients enrolled in the study, but we're optimistic that another 12 months of data will demonstrate that even very small amounts of disease detected only by molecular methods can have clinical significance," Tafra concluded.

SOURCE:
Department of Defense Breast Cancer Research Program meeting, Orlando, Florida, September 26, 2002