A genomic test may help some women with early-stage breast cancer gauge the risk of a recurrence and the potential benefit of additional chemotherapy even when the disease has spread to the lymph nodes, researchers are reporting.

The test, OncotypeDX, profiles the activity of 21 genes in a tumor and quantifies the risk of a recurrence over 10 years, assuming the patient receives 5 years of hormonal therapy such as tamoxifen.

Many physicians have used the test to help identify women with estrogen receptor (ER)-positive disease that has not spread to the lymph nodes whose risk of a recurrence is so low that they might not benefit from additional chemotherapy after surgery.

Now, researchers say the test could also predict which postmenopausal women with node-positive, ER-positive disease would benefit from adjuvant chemotherapy and define a group for whom chemotherapy does not appear to be beneficial.

"This test allows physicians to discover the biologic profile of an individual cancer and treat the patient accordingly," said Dr. Kathy Albain of the Cardinal Bernardin Cancer Center of Loyola University Chicago, who presented the findings last week at the San Antonio Breast Cancer Symposium. The test could be an aid right now in making treatment decisions for certain patients, but should be used selectively, she said.

The study, led by the Southwest Oncology Group, used tumor samples from 367 women who had been treated either with tamoxifen alone or with anthracycline-based adjuvant chemotherapy followed by tamoxifen. A high "recurrence score" predicted a high risk of recurrence and a large benefit from chemotherapy, while a low recurrence score identified a group of women who did not seem to benefit from the added chemotherapy.

Even though the test identified a group with the lowest risk of recurrence in the study sample, there still was a 40 percent rate of recurrence at 10 years in the subset. "This tells us that these patients with positive nodes and low recurrence scores need a different treatment strategy that will improve the 10-year outcomes," said Dr. Albain.

The results confirm previous studies involving node-negative disease and slightly different chemotherapy regimens. "A general picture is emerging that this test is able to distinguish patients who appear to likely benefit from chemotherapy," said Dr. Peter Ravdin of the University of Texas M.D. Anderson Cancer Center and a coauthor of the abstract. "And that's exciting."

Many in the field have wondered whether all node-positive breast cancers are the same or whether physicians should be trying to individualize treatment. "This study showed that even in node-positive breast cancer, all women do not benefit equally from chemotherapy," said coauthor Dr. Steven Shak of Genomic Health, which makes the test.

The findings support the fact that biology is the most important predictive factor for a benefit from chemotherapy since the recurrence scores are predictive in patients with both node-positive and node-negative disease, said Dr. Sandra Swain of the Washington Cancer Institute at the Washington Hospital Center in the District of Columbia, who attended the presentation.

"It's very exciting to have a test like this," she added. "We are beginning to home in on the true biology of the tumor and think critically about which patients need treatment."

The study was small and needs to be confirmed. More research is also needed to determine whether commonly available biological markers such as the gene HER2/neu and the estrogen receptor could provide essentially the same information about responsiveness to chemotherapy as the gene signature, according to Dr. Ravdin.

Classical biological factors might be a simpler and less expensive way to achieve the same result, said Dr. Ravdin, noting that the test costs approximately $3,500. "We owe it to our patients to explore this question further."

The researchers plan to publish the findings next year, including data on the use of combinations of classical biological markers in these patients.

— Edward R. Winstead