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

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 of the National Cancer Institute–sponsored Trial Assigning Individualized Options for Treatment (Rx), or TAILORx trial.^1,2 Patients with an RS of <11 who were treated with hormone therapy alone had <1% chance of distal recurrence at 5 years, and <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 the 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,” said Joseph Sparano, MD, Montefiore Medical Center, Bronx, NY. “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

“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,” he added.²

The authors 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 the patients included in the trial had hormone receptor–positive, node-negative, HER2-negative breast cancer with tumors of 1.1 cm to 5 cm in the greatest dimension for a tumor of any grade or tumors of 0.6 cm to 1 cm in the greatest dimension in intermediate- or high-grade tumors. These women met established guidelines for considering adjuvant chemotherapy, Dr Sparano emphasized. Patients’ tumor samples were tested with the 21-gene Oncotype DX assay to calculate RS.

Of all the 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

Dr 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 chemotherapy plus endocrine therapy, or endocrine therapy alone. It is important to determine the effect of chemotherapy in this intermediate-risk group, Dr 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, NY, 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,” Dr Hudis 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 Dr Hudis said that it is critical to determine the role of chemotherapy in this newly defined 11 to 17 RS group, “since there will be 2 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 Dr Hudis made is that Oncotype DX is 1 of several genetic tests for predicting the benefit of chemotherapy. “A less expensive and broadly distributed test would be valued 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 1 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 2015; September 25-29, 2015; Vienna, Austria. Abstract 5BA. www.europeancancercongress.org/Scientific-Pro gramme/Abstract-search?abstractid=20456. Accessed September 30, 2015.
2. Sparano JA, Gray RJ, Makower DF, et al. Prospective validation of a 21-gene expression assay in breast cancer. N Engl J Med. 2015 Sep 28. Epub ahead of print.
3. 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. N Engl J Med. 2015 Sep 28. Epub ahead of print.