FDA Okays Gene Test to Predict Breast Cancer Recurrence

ROCKVILLE, Md., Feb. 6 -- The FDA said today it has approved the first microarray genetic analysis designed to aid in predicting the risk of stage I or II breast cancer recurrence or metastasis.

MammaPrint, an in vitro multivariate index assay, measures 70 gene markers in tumors. Those signals are then used to calculate an index to predict likelihood of recurrence or metastasis.

A woman identified as high risk on the basis of this index "is about twice as likely to see recurrent breast cancer as a woman identified as low risk," said Steven Gutman, M.D., director of the agency's Office of In Vitro Diagnostic Device Evaluation.

Dr. Gutman spoke a press conference at which he touted the approval as a significant advance, while at the same time cautioning that it was "not a test that you can take to the bank."

For example, the positive predictive value at five years was 23% and just 29% at 10 years, while the negative predictive value was 95% at five years and 90% at 10 years.

The message, Dr. Gutman said, was that "the test provides valuable biologic information about the tumor," but that information has to be interpreted by experienced oncologists who will integrate the information into a clinical profile of the patient.

Dr. Gutman said in reply to a question that the test was likely to help guide adjuvant therapies, but, noting that he was not an oncologist, declined to offer specifics.

The FDA clearance was based on data from a study using tumor samples and clinical data from 302 patients at five European centers. These studies confirmed that the microarray was useful in predicting time to distant metastasis in women who are under age 61 with stage I and II disease and who have tumor size equal to or less than 5 cm and node negative.

The FDA plans to publish a special guidance document within the next 60 days describing types of data that should support claims for genetic profiling for breast cancer prognosis.

Although this is the first FDA-approved microarray test, it is not the first genetic test on the market. But Dr. Gutman said the other genetic tests "are looking for a single signal, not 70 signals."

MammaPrint was developed by Agendia, a laboratory located in Amsterdam, The Netherlands, where the product has been on the market since 2005.

Dr. Gutman said Agendia will market the test in the United States, but will not sell test kits here. Tissue samples, he said, will be sent to Amsterdam for analysis in the Agendia lab. "With FedEx, the turn around time should be about two days," he said.

Noting that today's action was a first, Dr. Gutman said that several months ago, the FDA issued a draft guidance document concerning the need for these complex molecular tests to meet pre-market review and post-market device requirements even when the tests are developed and used by a single laboratory.

Although the FDA regulates diagnostic tests sold to laboratories, hospitals and physicians, it uses discretion when regulating tests developed and performed by single laboratories, a group of tests known as home brew assays.

On Thursday, the FDA will hold a public meeting to discuss its draft guidance document describing its regulatory approach to this type of test.