Oncotype DX Breast Cancer Assay Spares Low-Risk Patients from Chemotherapy

European Cancer Congress

Patients with early breast cancer and a low Oncotype DX Recurrence Score (RS) can be safely treated with hormone therapy alone and avoid chemotherapy, according to results from the National Cancer Institute–sponsored TAILORx trial.^1,2 Patients who had an RS of <11 treated with hormone therapy alone had less than a 1% chance of distant recurrence at 5 years and less than a 2% chance of recurrence at any site at 5 years.

Outcomes were excellent regardless of patient age, tumor size, and tumor grade in these node-negative, estrogen receptor–positive, HER2-negative patients who met the guidelines for consideration of chemotherapy in addition to hormone therapy.

This study validates use of Oncotype DX to guide therapy in low-risk patients (RS 0-10). The TAILORx study results were published simultaneously online in the New England Journal of Medicine² to coincide with presentation of the results at the 2015 European Cancer Congress (ECC 2015).¹

“This is the first prospectively conducted clinical trial evaluating this multigene test—or any breast cancer multigene test for that matter—in which patients with early-stage breast cancer were uniformly treated based on their [Oncotype DX] test results. The compelling results seen in this global study provide unequivocal evidence supporting the clinical utility of Oncotype DX to risk-stratify patients with early-stage breast cancer,”³ said Joseph Sparano, MD, Montefiore Medical Center, Bronx, NY.

“These findings provide additional evidence supporting expert-derived clinical practice guidelines that recommend the use of this assay in patients with hormone receptor–positive, axillary node–negative invasive breast cancer,”² he added.

The study enrolled 10,273 patients from 1182 community-based medical centers and major cancer centers in the United States, Canada, Peru, Ireland, Australia, and New Zealand.³ All patients enrolled in the trial had hormone receptor–positive, node-negative, HER2-negative breast cancer with tumors of 1.1 to 5 cm in the greatest dimension for a tumor of any grade or tumors of 0.6 to 1 cm in the greatest dimension in intermediate- or high-grade tumors. These women met established guidelines for considering adjuvant chemotherapy, Sparano emphasized.

Patients’ tumor samples were tested with the 21-gene Oncotype DX assay to calculate the RS.

Of all patients enrolled in the trial, 1629 (15.9%) with an RS of 0 to 10 were assigned to receive endocrine therapy alone without chemotherapy.² At 5 years, the rate of invasive disease-free survival was 93.8%, the rate of freedom from distant recurrence of breast cancer was 99.3%, and the rate of freedom from recurrence of breast cancer at either a distant or locoregional site was 98.7%; the rate of overall survival was 98%.²

Sparano pointed out that only 16% of patients enrolled in TAILORx are considered low risk (RS 0-10). Another 67% of those enrolled had a midrange RS of 11 to 25 and were randomized to receive either chemotherapy plus endocrine therapy or endocrine therapy alone. It is important to determine the effect of chemotherapy in this intermediate-risk group, Sparano said.

In his editorial in the New England Journal of Medicine, Clifford A. Hudis, MD, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York City, hailed these results enthusiastically.

“These results cannot come soon enough, given the already widespread adoption of the test as a key component of guidelines and routine clinical decision making,” he stated.⁴

The cutoff for low-risk patients using Oncotype DX is set by the company at 0 to 18, but the study reported at ECC 2015 focused only on patients with an RS of 0 to 10.¹ Hudis said it is critical to determine the role of chemotherapy in this newly defined 11 to 17 RS group, “since there will be two conflicting guides to their treatment that need to be reconciled: the cutoff point used in this trial and the previously available cutoff point that is associated with the commercial test.”⁴

Another important point Hudis made is that Oncotype DX is one of several genetic tests to predict the benefit of chemotherapy. “A less expensive and broadly distributed test would be valuable globally. 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.”⁴

References

1. Sparano J, Gray R, Zujewski JA, et al. Prospective trial of endocrine therapy alone in patients with estrogen-receptor positive, HER2-negative, node-negative breast cancer: results of the TAILORx low-risk registry. Presented at: European Cancer Congress; September 25-29, 2015; Vienna, Austria. Abstract 5BA.
2. Sparano JA, Gray RJ, Makower DF, et al. Prospective validation of a 21-gene expression assay in breast cancer [published online September 28, 2015]. N Engl J Med.
3. PR Newswire. Large TAILORx outcomes study demonstrates 99% of patients with low Oncotype DX Recurrence Score results were breast cancer relapse-free following five years of hormone therapy alone [news release]. Geneva, Switzerland: Genomic Health; September 28, 2015. www.prnewswire.co.uk/news-releases/large-tailorx-outcomes-study-demonstrates-99-of-patients-with-low-oncotype-dx-recurrence-score-results-were-breast-cancer-relapse-free-following-five-years-of-hormone-therapy-alone-529730651.html. Accessed September 30, 2015.
4. Hudis CA. Biology before anatomy in early breast cancer—precisely the point [published online September 28, 2015]. N Engl J Med.

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