Results from several studies presented last week at a major research conference validate that a new test can predict the risk of breast cancer recurrence in a sizable group of patients; the studies also appear to identify which of those patients will benefit most from chemotherapy. The studies were heralded by researchers as an important moment in the move toward individualized cancer care. Central to the investigations is a test, Oncotype DX, that analyzes the expression of a 21-gene panel in biopsy samples from women with estrogen-dependent, lymph-node negative breast cancer, which accounts for more than 50,000 breast cancer cases in the United States each year.

The results, presented at the San Antonio Breast Cancer Symposium, "are some of the most striking I have seen in breast cancer," said Dr. Jo Anne Zujewski, a senior investigator in the NCI Cancer Therapy Evaluation Program, during a news conference.

Confirmation of earlier data on the ability of the assay - developed by Genomic Health Inc., which, along with NCI, funded some of the studies - to accurately predict recurrence risk was needed. What was lacking, some breast cancer researchers had argued,was data on whether the assay could forecast chemotherapy benefit, which would help guide treatment decisions.

An analysis of biopsy samples from patients in the tamoxifen plus chemotherapy arm of the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-20 study using the assay, Oncotype DX, appears to answer that question. According to the lead investigator, Dr. Soonmyung Paik, patients with high "recurrence scores" on the assay (31 or higher on a 0 to 100 scale) had a significant benefit from chemotherapy (27.6 percent absolute increase in distant relapse-free-survival at 10 years). Patients with low recurrence scores (18 or lower), on the other hand, essentially received no benefit from chemotherapy. According to these results, about one-quarter of patients with node-negative, receptor-positive breast cancer are at high risk for recurrence and would benefit from chemotherapy in addition to tamoxifen, while about half of patients are at low risk and would not.

"I think the data indicated clearly that the benefit of chemotherapy is not uniform," said NSABP Chair Dr. Norman Wolmark.

The presentation of these data coincided with the New England Journal of Medicine's online publication last week of results from the first large-scale study using Oncotype DX on archival samples from NSABP. These data were initially presented last year and showed that the actual breast cancer recurrence rate was 6.8 percent at 10 years in patients with low recurrence scores, 14.3 percent in the intermediate score group, and 30 percent in the high score group.

The Oncotype DX assay is considered a breakthrough because it can be used on tumor specimens that are fixed and embedded in paraffin. This has been technically difficult to do because RNA is altered when stored in this fashion. Researchers at Genomic Health Inc., however, developed a method for performing genetic analyses that allows them to use the altered RNA, making testing of patient samples readily accessible to clinicians in all settings. Currently, Genomic Health's California-based headquarters is the only facility licensed to perform the test.

NCI will conduct a randomized, prospective clinical trial involving all the clinical trials groups that study breast cancer. The trial will use Oncotype DX to identify patients with recurrence scores in the intermediate range to determine whether they benefit from chemotherapy. "That's the group for whom we really don't know how well this test will perform," Dr. Zujewski said.