A 21-gene test is accurate in predicting which women diagnosed with certain types of breast cancer will do well with hormone therapy alone and can forego chemotherapy, according to a recent study in the New England Journal of Medicine. The ongoing study, called the Trial Assigning IndividuaLized Options for Treatment (Rx), or TAILORx, provides new evidence on the test called Oncotype DX.
The test, already on the market in the United States and other countries, examines the activity of 21 genes in tumor samples taken from women during breast cancer surgery. The results are used to calculate a score between 0 and 100. The lower the score, the lower the chance the cancer will spread if only hormone therapy is prescribed, such as the drug tamoxifen.
The clinical trial was conducted at multiple medical centers and enrolled over 10,000 women. The women all had a type of breast cancer that would likely respond to hormone therapy (ER/PR positive, HER2/neu negative) and their cancer had not spread to the lymph nodes. (Cancer spread to lymph nodes is usually a reason to have chemotherapy.) However, the women's tumors had other features (large size, intermediate or high grade) that indicated that chemotherapy might be needed in addition to hormone therapy.
Women in the trial whose tumors scored 10 or lower on the Oncotype DX test received standard hormone therapy but did not undergo chemotherapy. Almost 16% of the women in the study had a score of 10 or lower. They were monitored closely for five years. At that point, the researchers determined that overall survival rate was 98% for this group and the risk that the cancer would return was 6% at five years.
"This should provide a lot of reassurance to women and their physicians," says the study's senior author, Kathy S. Albain M.D., Professor of Medicine at the Loyola University School of Medicine. "In women whose breast cancer scored low on the multigene test, there was outstanding survival with endocrine (hormone) therapy alone. The test provides us with greater certainty of who can safely avoid chemotherapy," said Albain.
A question was raised about difference in the "low-risk" cutoff value used in the study and the standard one used in clinical practices currently. In an editorial that appeared in the same issue of New England Journal of Medicine, Clifford Hudis, MD, head of the Breast Cancer Service at Memorial Sloan Kettering Cancer Center wrote, "For patients in this new 'lower risk' group, it is clearly helpful, if broadly anticipated. However, for the many physicians already using the test, the gap between this cutoff point of 10 and the higher 'standard' cutoff point of 18 may be a concern."
Hudis adds that while more tests, and less expensive tests, for this use are likely to be developed, "For now, however, this assay is the most rigorously tested option and provides proof of the principle that we can develop reproducible predictive tests to select patients who should not receive chemotherapy. In that regard, it is one more step toward precision, there are more steps ahead."
An additional 68% of women in the study had a mid-range score of 11 to 25. This second set of women were randomly assigned to receive either hormone therapy plus chemotherapy or hormone therapy alone. These women are still being followed and results are not yet available.