A series of new studies conducted in breast cancer patients in Europe and Asia have added further evidence that the Oncotype DX multi-gene expression test can help predict recurrence and guide treatment decisions for certain early node-negative breast cancers that are estrogen-receptor positive and/or progesterone-receptor positive. The test analyzes the activity of 21 genes within a breast cancer patient's tumor to help determine the likelihood of recurrence and whether patients will benefit from adding chemotherapy.
The test is also the only assay incorporated in the ASCO and NCCN breast cancer treatment guidelines for patients with node-negative breast cancer that is ER-positive and/or PR-positive.
The new findings were presented earlier this year at the St. Gallen International Breast Cancer Conference, adding to the 13 clinical studies involving some 4,000 breast cancer patients around the world. A large validation study was published in the New England Journal of Medicine in 2004 and a chemotherapy benefit study was published in the Journal of Clinical Oncology in 2006.
Long-term follow-up in those published studies have shown that findings have remained valid for at least 14 years, noted Steven Shak, MD, a co-founder and the Chief Medical Officer of the test's manufacturer, Genomic Health.
“The test assigns a Recurrence Score of 0 to 100, based on the genetic analysis, with higher scores indicating greater risk and clear chemotherapy benefit and lower ones associated with low risk and minimal, if any, chemotherapy benefit.”
The Oncotype DX assay is currently covered by about 90% of health insurers in the United States, at a cost of $4,075, and the patient's Recurrence Score results are sent to the ordering physician within about two weeks from the time the tumor tissue is received, although the current average turnaround is seven days, Dr. Shak said. “It is estimated that more than half of all patients in the U.S. now undergo the tumor testing, and we have conducted over 190,000 assays to date.”
In 2006, the National Cancer Institute launched TAILORx (Trial Assigning IndividuaLized Options for Treatment), which was designed to evaluate the effect of chemotherapy in women with a mid-range risk of cancer recurring, as determined by the Oncotype DX breast cancer score. The trial will evaluate the effect of chemotherapy only for those with a midrange recurrence score, as has been demonstrated by previous studies of the assay.
These studies have already confirmed the benefit of adjuvant chemotherapy for those in the high recurrence score range, and minimal, if any, benefit for those with low scores.
TAILORx was the first clinical trial launched by 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. The study met its recruitment goal of nearly 10,000 patients last year.
The St. Gallen data showed that test results changed treatment decisions in one third of cases. Research reported from Singapore and Greece also indicated that use of the test would be very cost-effective. A meta-analysis of nine published decision-impact studies, including 1,154 early-stage breast cancer patients, showed an approximately 35% change in treatment decisions based on the Oncotype DX results, with an overall reduction in chemotherapy recommendations or use of 24 percent.
In a study by German researchers, results from 149 early-stage breast cancer patients with node-negative disease and 48 patients with node-negative disease showed that the test score had an impact on adjuvant treatment decision-making, with changes in 38% of node-negative cases and 48% of node-positive cases, with a 17% reduction in chemotherapy.
And researchers from Greece reported that the test resulted in reclassification of risk assessment of risk and likelihood of chemotherapy benefit in more than 50% of patients compared with the traditional criteria, while a Japanese study of 142 patients demonstrated that conventional pathological factors were not equivalent to the use of the test in treatment decisions for early-stage breast cancer patients.
Several of the other international studies also showed that the test had a positive impact on patient quality of life as well as economic savings associated with chemotherapy.
‘A Major Shift’
Larry Norton, MD, Deputy Physician-in-Chief for Breast Cancer Programs at Memorial Sloan-Kettering Cancer Center and Director of the Evelyn H. Lauder Breast Center, called the Oncotype DX test a “model” of how similar tests should be developed in the future.
The assay was developed “as well as any test like this can be developed,” he said. “This is an ongoing process, with a lot of researchers determining its validity, and its use is growing, in part because of the economic benefits but also due to increasing patient demand.
“By providing solid molecular gene expression data to help treatment decisions, one-third or more of women can be spared from chemotherapy, which can result in significant health care savings.”
Dr. Norton, who has no financial interest in Genomic Health or its product, said that the treatment landscape is changing from using chemotherapy whenever cancer is detected.
“There is a revolution happening in [oncological] clinical decision-making, and we are in the very early stages of changing from the traditional one-size-fits-all chemotherapy approach in cancer patients to molecular and genetic profiling of tumors. This is a major shift,” he said.
Lajos Pusztai, MD, PhD, Professor of Medical Breast Cancer Oncology at the University of Texas MD Anderson Cancer Center, said in a telephone interview that studies of the test in the US and Canada have been “remarkably consistent” in identifying breast cancer patients for whom chemotherapy is not necessary.
“Every single one has shown that 35 to 40 percent of women with node-negative breast cancers that are estrogen-receptor positive and/or progesterone-receptor positive have been reassigned to a lower-risk category and have been spared the expense and physical problems of chemotherapy. The evidence has been unequivocal.”
That these newer studies in foreign countries have shown the same is encouraging, he noted. “What this test does is give us a rationale for avoiding chemotherapy in these women. These new findings are very reassuring.”
The findings are similar to those reported by Dr. Pusztai and his colleagues published last year in Cancer (2010:116:5161-5167).
“We found the same thing,” he said. “Most oncologists order the test for Stage I cancer, and in that cohort the test is between 50 and 60 percent informative, but high-risk patients still represent between 85 and 90 percent of cases.
“It can be very difficult to objectively differentiate between these patients, but there is a 10-fold difference between them and those with lower-risk cancers in terms of the need for chemotherapy.”
The test has been widely used in the US for three to four years now, and there has been an exponential curve in its gradual adoption, Dr. Pusztai said. But because recurrence in lower-risk patients typically takes three to six years, and long-term outcome studies require large groups of patients, it remains to be seen whether remission rates will stay down in patients who do not receive chemotherapy, he said.
“Although the available long-term risk data is encouraging, we simply can't tell yet.”