The recently published updated St. Gallen International Breast Cancer Guidelines reinforced the important role of genomic testing in the treatment of early breast cancer.1 In particular, the Oncotype DX Breast Recurrence Score® test was recognized for its prognostic ability as well as its value in guiding treatment decisions on when physicians may decide to omit chemotherapy for patients with up to 3 positive nodes.

Cancer Therapy Advisor spoke with Calvin Chao, MD, Vice President of Global Medical Affairs, Genomic Health, Inc., in Redwood City, California, about how the Oncotype DX® test is implemented, how results can guide treatment, its use globally, and the future of prognostic testing for patients with ductal carcinoma in situ (DCIS).

Cancer Therapy Advisor (CTA): Guide readers through the thought processes regarding how a physician would initially opt to use a test to guide adjuvant chemotherapy treatment decisions and how Oncotype DX would be selected versus the other currently available genomic biomarkers tests?

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Dr Chao: Let’s start by talking about ER-positive, HER2-negative breast cancer for patients who have no involvement of their lymph nodes. This is the most common presentation for breast cancer. Studies show that out of 100 such patients, only about 4 or 5 will benefit from adjuvant chemotherapy. So, given this low probability of benefit from chemotherapy, it’s important to really make sure that the patients who use chemotherapy are most likely to be the ones who would receive that benefit.

Now, it’s true that there are multigene assays available on the market that can tell you about the risk of recurrence. This is what we call prognostic. Prognostic assays can tell if a patient is likely to have recurrence (or not) if they receive hormone therapy alone; in other words, if they don’t receive chemotherapy. As such, that can be helpful information, but I think it’s important to know that to date, only one assay has achieved validation studies to predict a benefit from chemotherapy, and that is the Oncotype DX Breast Recurrence Score. That’s why in the United States, Oncotype DX remains the most widely used assay available.

With all other assays available, it’s also important to look at the strength and the completeness of validation evidence. As an example, there are some assays whose evidence is limited to postmenopausal women only; this would include Prosigna and EndoPredict. These assays could be useful in assisting with risk of recurrence questions in patients who are postmenopausal, but they really don’t have any validation data in younger premenopausal patients receiving hormone therapy alone.

It is important to have prospective evidence. Many validation studies have been done on archived tumor tissue. It means they were done on clinical trials or cohorts of patients who have had cancer in the past and have had their clinical outcomes documented. When these studies are done, archived tumors can generate multigene assay results and one can then statistically associate those results with the actual clinical outcomes. These are called prospective/retrospective studies. It’s a complex term because they are studies in historical samples but they are being analyzed in a prospective fashion.

For the Oncotype DX assay, initial findings from the prospective Trial Assigning Individualized Options for Treatment (Rx) (TAILORx; Identifier: NCT00310180) were published in the New England Journal of Medicine for patients with Recurrence Score results of less than 11.2 These results gave a huge amount of reassurance to the 1626 patients with the lowest Recurrence Score results, all of whom did not receive chemotherapy, as 99.3% of patients were alive with no evidence of distant recurrence at 5 years.

More recently, there has been prospective real-world evidence from patients using the Oncotype DX test. This includes the SEER registry, which has captured data in 12 states within the United States from all patients tested with the Oncotype DX assay since its introduction in 2004. In this registry, the Recurrence Score result accurately predicted breast cancer mortality. We found the risk of dying from breast cancer in 5 years was only 0.4% for node-negative patients with low Recurrence Score results under 18, despite the vast majority of these patients having avoided chemotherapy.3