GeneSearch BLN Assay gets FDA approval for node assessment during surgery

ROCKVILLE, Maryland—The Food and Drug Administration has approved the GeneSearch Breast Lymph Node (BLN) Assay, an intraoperative, molecular-based test for determining whether breast cancer has metastasized to nearby lymph nodes. The agency acted after reviewing data from a pivotal study that investigated the test in a clinical trial involving 416 women who had surgery for breast cancer (see Oncology NEWS International, February 2007, page 1).

Data from more than 300 women tested in clinical trials in the United States have shown that the test can identify 95.6% of women with metastatic cancer cells in their lymph nodes while their surgery is in progress, according to the manufacturer Veridex, LCC, a Johnson & Johnson company.

"The GeneSearch BLN Assay offers a new approach to sentinel node testing," said Daniel Schultz, MD, director of the FDA's Center for Devices and Radiological Health, in announcing the approval. "Results of this rapid test are available while patients are on the operating table, providing a way for some women to avoid a second operation."

Veridex estimates the test could spare as many as 5,200 women a year in the United States from undergoing second surgeries to remove lymph nodes found to contain metastatic cancer as determined by an extensive microscopic examination following surgery. This is based on an estimated 52,000 node-positive patients each year, with 95% (49,400) identified as positive by GeneSearch, compared with 85% (44,200) by frozen section, the other intraoperative test.

Real-Time Diagnostic Test

GeneSearch is intended as a real-time, qualitative, in vitro diagnostic test for rapidly detecting metastases larger than 0.2 mm in sentinel node tissue removed for biopsy from breast cancer patients. It uses a reverse transcriptase-polymerase chain reaction (RT-PCR) assay to detect the gene expression markers mammaglobin and cytokeratin-19, which are abundant in breast tissue but sparse in lymph nodes.

The test allows for the analysis of 50% of the sentinel nodes, compared with 5% of tissue typically examined microscopically for evidence of cancer cells. Test results from tissues taken early in the surgery are available in 35 to 40 minutes.

In the pivotal trial submitted to FDA, researchers led by Pat W. Whitworth, MD, director of the Nashville Breast Center, reported results from 416 women whose sentinel nodes were tested using GeneSearch while they were in surgery. Their diagnoses were invasive ductal breast cancer, alone or in combination with other types (80.4%); invasive lobular cancer (13.9%); and an invasive cancer other than lobular or ductal (5.7%). Most patients were stage I or II (94.3%), with 5.3% stage III and 0.5% stage IV. The mean primary tumor size was 1.9 cm.

Compared to overall histology in the 416 patients, GeneSearch had a sensitivity of 87.6% and a specificity of 94.2%. In 383 patients with valid assay results, again in comparison to overall histology, GeneSearch had a sensitivity of 90.6% and a specificity of 93.6%.

"With this new molecular pathology test, we have an opportunity to improve the standard of care for women with this disease," Dr. Whitworth said. "Patients and physicians can now have a higher degree of confidence in their lymph node test results and, thus, make more informed decisions about their treatment."

Veridex has committed to two phase IV trials, one to substantiate GeneSearch's turnaround time when used intraoperatively and another, with more than 1,000 patients, to further substantiate the accuracy of the test. "With the GeneSearch BLN Assay," said Ken Berlin, general manager, Veridex, "we now have the opportunity to detect some metastases that could be missed by other tests. The end result is better patient management and a better patient standard of care."