ORLANDO-A study reported at the Era of Hope Department of Defense Breast Cancer Program meeting adds more evidence supporting wider use of sentinel lymph node (SLN) biopsy by surgeons skilled in the technique.
ORLANDOA study reported at the Era of Hope Department of Defense Breast Cancer Program meeting adds more evidence supporting wider use of sentinel lymph node (SLN) biopsy by surgeons skilled in the technique.
"We wanted to see if we could use sentinel node biopsy for a diverse group of patients," said Lorraine Tafra, MD, director of The Breast Center at the Anne Arundel Medical Center, Annapolis, Maryland. "And as it turns out, the vast majority of breast cancer patients can benefit from sentinel node biopsy."
The ongoing multicenter trial began in 1997 to determine which factors may increase the chance of false-negative results from sentinel node biopsy. The study has enrolled 1,236 patients. Results of sentinel node biopsy have been compared with axillary node dissection in a group of 780 patients who underwent both procedures.
On most patients, surgeons used a peritumoral and/or intradermal injection technique, with both technetium sulfur colloid and isosulfan blue dye. A small group also were injected with periareolar fluorescein. Intraoperatively, a variety of all commercially available gamma probes were used to detect the sentinel nodes.
The study found three factors that significantly increased the risk of a false-negative result: Prior extensive surgery in the breast, significant disease in the lymph nodes, and the number of sentinel nodes found by the surgeon. Dr. Tafra surmised that prior surgery interrupted the normal lymph flow, extensive disease in the lymph nodes blocked the dye from arriving, and inexperienced surgeons often missed additional sentinel nodes.
"You’ve got to find the sentinel nodes," she explained. "If you find one, look around for more. Most patients have two. If you miss the second node, you may miss the node that contains metastatic disease. The metastatic disease is not always in the first sentinel node that is removed."
The data showed no association between false negatives and patient age, tumor type, tumor location, multiple vs single site disease, or neoadjuvant chemotherapy.
Dr. Tafra’s research also indicates that the technique used to analyze sentinel node biopsy tissue may affect the accuracy of the results. The team examined 38 false-negative specimens from 19 patients using a molecular testreverse transcription polymerase chain reaction (RT-PCR)which amplifies the signal from the tumor. It increases sensitivity as compared to standard pathology tests. In addition, using RT-PCR, the investigators sampled the tissue from throughout the node, rather than a few sentinel sections. With RT-PCR, cancer cells were seen in 55% of the false-negative nodes.
This part of the research is ongoing. To date, only half the false-negative specimens have undergone RT-PCR analysis. Dr. Tafra believes her final report will show that tiny amounts of disease found with molecular methods will have clinical significance. Early data reveal longer disease-free survival for patients with negative sentinel nodal biopsies by both standard pathology and molecular testing, suggesting that the cancer truly had not spread.
The investigators also assessed the use of sentinel node biopsy in patients with ductal carcinoma in situ (DCIS), in whom lymph nodes are not routinely biopsied. The study found that 4% of the women with DCIS had cancer in the lymph nodes, although there was no prior evidence of invasive disease. The investigators concluded that sentinel node biopsy can identify the small number of DCIS patients who could benefit from more aggressive treatment.
"Sentinel node biopsy is accurate in a diverse group of patients," Dr. Tafra concluded. "A vast majority of patients can benefit. Its accuracy should be questioned if the surgeon is not experienced, which we define as 20 to 40 cases, and where there is extensive disease, prior surgery, or only one sentinel node has been found."