NSABP Study Confirms Oncotype DX Predicts Chemotherapy Benefit in Breast Cancer Patients

The Journal of Clinical Oncology has published results of a large-scale trial conducted with the National Surgical Adjuvant Breast and Bowel Project (NSABP) confirming that the Oncotype DX 21-gene panel, which quantifies the risk of breast cancer recurrence, also predicts the likelihood of response to chemotherapy in a large portion of women with early-stage breast cancer. This study successfully challenges the common assumption that all women benefit similarly from chemotherapy and follows the publication of an earlier large Oncotype DX study published in The New England Journal of Medicine in 2004.

The study was published online as an "early release" to coincide with the launch of TAILORx (Trial Assigning IndividuaLized Options for Treatment [Rx]), a first-of-its-kind individualized treatment trial that will utilize Oncotype DX to identify and assign treatment to more than 10,000 women from 900 sites in the United States and Canada. Findings from the NSABP study helped guide the development of the TAILORx trial, which was recently announced by the National Cancer Institute (NCI).

Implications of Recurrence Score

Oncotype DX uses RNA analysis of tumor tissues to measure the expression profile of a panel of 21 genes demonstrated to be involved in breast cancer, including those related to the estrogen receptor, the HER2 gene and proliferation, as well as several other pathways. Based on results of the test, a recurrence score from 0 to 100 is determined.

"The clinical implications of these results for patients with low or high recurrence scores are clear, and have helped guide subsequent treatment decisions for many women following their original presentation at the 2004 San Antonio Breast Cancer Symposium," said Soonmyung Paik, MD, director of the NSABP Division of Pathology. "With TAILORx, we hope to gain a better understanding of the effects of chemotherapy for those patients with midrange scores, building upon what we've already learned in an effort to individualize treatment for all women with early-stage breast cancer."

The NSABP B-20 chemotherapy benefit study evaluated 651 patients (227 randomized to tamoxifen and 434 randomized to tamoxifen plus chemotherapy). Results demonstrated that breast cancer patients with high recurrence scores and high risk of recurrence, as identified by the Oncotype DX assay, had large benefits from chemotherapy. Patients with low recurrence scores and low risk of recurrence had only minimal, if any, benefit from chemotherapy. The magnitude of chemotherapy benefit could be predicted from the recurrence score. These results led to the TAILORx trial, which aims to assess the effects of chemotherapy in a group of women with midrange recurrence scores and risk of recurrence.

TAILORx Study

Coordinated by the Eastern Cooperative Oncology Group (ECOG), TAILORx is designed to evaluate the effect of chemotherapy in women with a midrange risk of their cancer returning, as determined by Oncotype DX, Genomic Health's breast cancer test service that quantifies the likelihood of breast cancer recurrence and predicts the likelihood of response to chemotherapy for many early-stage breast cancer patients. TAILORx will be one of the largest adjuvant treatment trials in breast cancer ever conducted, and recently opened to begin enrolling newly diagnosed women throughout the country.

Major Initiative

"TAILORx represents the culmination of a major initiative to integrate molecular diagnostic testing into clinical decision-making," said Joseph Sparano, MD, principal investigator for the ECOG and director of the Breast Evaluation Center at the Montefiore-Einstein Cancer Center in New York. "This is the first trial from the NCI's Program for the Assessment of Clinical Cancer Tests (PACCT), which seeks to individualize cancer treatment by using, evaluating, and improving the latest diagnostic tests. Oncotype DX makes this trial possible by enabling us to separate women with high and low scores, whose treatment paths are clear, from those who fall in the midrange."

Researchers will utilize the Oncotype DX test to quantify each patient's individual risk of recurrence in order to assign them to the appropriate treatment. Women with a recurrence score greater than 25 will receive chemotherapy plus hormonal therapy; women with a recurrence score less than 11 will receive hormonal therapy alone; and those with a midrange recurrence score from 11 to 15, the primary study group, will be randomized to receive hormonal therapy with or without chemotherapy. This trial will evaluate the effect of chemotherapy only for those with a midrange recurrence score.