A commercially available genetic test reliably predicts the magnitude of chemotherapy benefit in women with estrogen receptor-positive, lymph node-negative breast cancer – potentially enabling tens of thousands of women per year to safely avoid the toxicities and expense of adjuvant chemotherapy. "This is a major breakthrough for the individualized treatment of patients diagnosed with early breast cancer." Soon-Myoung Paik, M.D., declared at a breast cancer symposium sponsored by the Cancer Therapy and Research Center.

      The 21 gene test, known as the Oncotype DX, was the subject of two large clinical studies and a favorable cost-benefit analysis presented at the San Antonio breast cancer symposium. The test, developed and marketed by Genomic Health Inc., previously was shown to predict the likelihood of distant recurrence of tamoxifen-treated note-negative breast cancer. In a new study, Dr. Paik applied the Oncotype DX to standard, routinely available tumor samples stored in paraffin blocks from 651 patients in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-20 trial, in which women with node-negative, estrogen receptor-positive breast cancer were randomized 1:2 to tamoxifen alone or tamoxifen plus chemotherapy.

      Current guidelines recommend adjuvant chemotherapy in the great majority of such patients, yet prior studies demonstrate the clinical benefit is concentrated in only about 15% of the treated population. That means roughly 85% of early-stage breast cancer patients are being overtreated with chemotherapy, explained Dr. Pate, director of the division of pathology at the and as a BP in Pittsburgh.

      A total of 25% of participants in the B-20 trial proved to have a high recurrence score on the Oncotype DX, meaning at least 31 / 100 points. Women in this group had a 10 year distant recurrence-free survival rate of 88% with chemotherapy and 60% without it. A total of 54% of the 20 participants had an Oncotype DX score below 18, defining them as low-risk. They derived essentially no benefit from chemotherapy. Doctor Paik's study was supported by the Nat. Cancer Inst., as well as Genomic Health. He is coholder of a patent for the polymerase chain reaction (PCR) assay used in the study.

      Tamoxifen-treated patients with a low recurrence score on the Oncotype DX test had a 2.8% mortality rate at 10 years, compared with 10.7% in those with an intermediate score of 18-30 and 15.5% in women with a high score. At a cost of $3,460, the test is pricey, although it is a highly complicated assay requiring 1000 individual steps. For reasons of quality control, it must for the time being be performed on samples shipped to the company's core laboratory. Despite the high price tag, a cost-benefit analysis reported at the meeting concluded that routine use of the assay is cost-effective. The potential savings through routine use of the 21 gene assay were greatest among patients at least 50 years of age, for whom empiric chemotherapy cost an average of $28,742 per year of life gained, compared with $16,108 using a selective strategy of Oncotype DX-guided chemotherapy.