Accuracy of Oncotype DX Confirmed for Patients with Early Stage Breast Cancer Treated with Aromatase Inhibitors

Previous studies have shown that the Oncotype DX Recurrence Score (RS) accurately estimates the risk of breast cancer recurrence in postmenopausal women with a diagnosis of invasive node-negative early stage estrogen-receptor (ER)—positive breast cancer who have undergone treatment with tamoxifen. The Oncotype DX molecular assay also helps clinicians select a chemotherapy regimen most likely to benefit the patient.

With a growing number of studies suggesting aromatase inhibitors (AIs) are superior to tamoxifen as an adjuvant treatment for early stage ER-positive breast cancer, researchers from the Royal Marsden Hospital in London, United Kingdom, decided to find out how Oncotype DX would fare in predicting distant recurrence for patients treated with AIs.

Using Oncotype DX, Mitch Dowsett, PhD, and colleagues from the ATAC Trialists’ Group analyzed tumor samples from 1231 women enrolled in the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial. All the patients had been treated previously for early stage ER-positive breast cancer with tamoxifen or anastrozole monotherapy. Researchers assessed rates of distant recurrence at 9 years and stratified patients according to the number of disease-affected lymph nodes, which ranged from 0 to >4. A total 872 patients (59%) were node-negative, and 306 (17%) were node-positive. The remaining 53 patients were node-status unknown.

Researchers classified an RS <18 as low risk, 18-30 as intermediate risk, and >31 as high risk. Distant recurrence rates at 9-year follow-up correlated with RS. For node-negative patients with a low-risk RS, 4% developed distant recurrence, as did 12% of those in the intermediate range and 25% with a high-risk RS. Distant recurrence rates were higher for node-positive patients: 17% in the low-risk group, 28% in the intermediate group, and 49% in the high-risk group. Researchers noted that regardless of the RS result, the rate of distant recurrence increased in accordance with the number of positive lymph nodes.

Investigators performed a multivariate analysis, adjusting for tumor size, grade, age, and treatment. Dr. Dowsett said, “Our multivariate analysis confirms that along with other standard measures such as tumor size, Oncotype DX contributes independently to providing a more complete picture of prognosis.” He added that the information provided by Oncotype DX would be useful in helping clinicians make chemotherapy decisions “for both node-negative and node-positive early stage breast cancer patients planned for either anastrozole or tamoxifen treatment.”

In addition to validating the benefit of Oncotype DX in predicting distant recurrence, researchers said they found a lower risk of recurrence in patients treated with AIs regardless of node status. At 5 years, the rate of recurrence was 9.1% in the tamoxifen monotherapy group versus 7.8% for those in the anastrozole group; at 9 years, 15.6% of women who received tamoxifen had experienced recurrence compared with 13.2% of women who took anastrozole.

Dr. Dowsett and associates evaluated the same set of patients using Adjuvant! Online. They concluded that Oncotype DX had “highly statistically significant predictive value for distant recurrence beyond that provided by Adjuvant! Online.”

As the use of AIs continues to expand, clinicians needed an accurate means to predict recurrence risk and help clinicians tailor chemotherapy to their patients with early stage ER-positive breast cancer. Dr. Dowsett said that his team’s study “demonstrated for the first time that RS is an independent predictor of distant recurrence in node-negative and node-positive hormone-receptor—positive patients treated with anastrozole.”