Breast Cancer Experts Question New Recommendations for 21-Gene Recurrence Score Assay

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At the 2016 San Antonio Breast Cancer Symposium, a group of breast cancer experts made a case for using the 21-gene Oncotype DX Breast Recurrence Score Assay in node-positive patients, despite ASCO’s latest recommendations to restrict it to node-negative estrogen receptor–positive patients.

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The most recent guidelines for the use of the 21-gene Oncotype DX Breast Recurrence Score reflect discordance between ASCO and the National Comprehensive Cancer Network® (NCCN®). “This has created confusion among practitioners, patients, and payers,” declared senior author Kathy S. Albain, MD, Director of the Breast Clinical Cardinal Bernardin Cancer Center.

A poster focusing on “a different take on the evidence” was presented in San Antonio by Eleftherios P. Mamounas, MD, of the National Surgical Breast and Bowel Project (NSABP) and Medical Director of the Comprehensive Breast Program at the University of Florida Health Cancer Center at Orlando Health.1 Dr. Mamounas and his team presented an analysis of the benefit of the recurrence score in node-positive disease, including all data published through 2016. (The ASCO guideline considered results published through 2014.)

“A comprehensive analytical review was conducted in 7 studies (over 8,000 patients) using the 21-gene recurrence score in node-positive, estrogen receptor–positive, early-stage breast cancer. These prospective-retrospective clinical trials and prospective outcome studies consistently identified patients with low number of positive nodes and a low recurrence score who did well without chemotherapy. Thus, the recurrence score consistently identifies low-risk patients with 1 to 3 positive nodes in whom chemotherapy can effectively and safely be avoided,” Dr. Mamounas and his team concluded.

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“Knowledge of the recurrence score results in node-positive breast cancer significantly decreased the frequency of adjuvant chemotherapy recommendations and provided a cost-effective and/or cost-saving approach worldwide, independent of local cost data,” they added.

In an interview with The ASCO Post, Dr. Albain said the results provide “additional reassurance” that there is, indeed, benefit to using the recurrence score assay in patients with one to three positive nodes. “I think the results tell us that in these patients, we can use the recurrence score assay as part of a careful discussion about the pros and cons of giving chemotherapy to the low recurrence score–lower node-positive risk group,” she said.

Dr. Albain added that some oncologists report having reimbursement issues, even in one to three positive nodes (not an issue in the past based on National Comprehensive Cancer Network [NCCN] guidelines), based on ASCO’s new recommendation against using the recurrence score assay in node-positive patients. “We are hoping that ASCO will quickly evaluate the new data and its recommendation,” she said.

Study Rationale

The use of the recurrence score assay in estrogen receptor-positive, HER2-negative, node-negative women was first incorporated into guidelines issued by ASCO and the NCCN in 2007 and 2008, respectively. In 2015, the NCCN updated its recommendation to allow for its use in women with one to three positive lymph nodes. In 2016, the ASCO Breast Cancer Guidelines Advisory Group and Clinical Practice Guidelines Committee took a different approach, making a “moderate”-strength recommendation that the “clinician should not use the 21-gene recurrence score to guide decisions” in patients with node-positive disease, calling the quality of the evidence “intermediate.”

According to Dr. Mamounas and his coauthors, this ASCO guideline was based on a review of two node-positive studies. It did not include data published after August 2014, which included four prospective outcomes studies showing that patients with low recurrence score results may be safely and effectively treated with hormone therapy alone. The committee also advised no change in node-positive clinical practice until the prospective Southwest Oncology Group (SWOG) S1007 study (RxPONDER) matures in several years. The discordant recommendations have led to confusion, the authors said, and may result in overtreatment of many patients.

To address this controversy, Dr. ­Mamounas and colleagues conducted a comprehensive analytic review of “the worldwide body of evidence” of the recurrence score assay in node-positive early breast cancer. They examined its use for prognosis, prediction of chemotherapy benefit, clinical utility/decision-making, and cost-effectiveness.

Benefit in Node-Positive Women

The researchers evaluated all published studies involving node-positive, estrogen receptor–positive early breast cancer with data from the recurrence score assay. They analyzed the studies according to their design and category of trial (validation, supportive, decision impact, cost-effectiveness, and prospective outcomes). Findings were obtained from 9,833 patients.

They identified 30 studies with clinical evidence supporting the value and utility of the recurrence score in node-positive, estrogen receptor–positive patients. A total of 7 studies employed a prospective-retrospective design or were prospective outcomes with clinical utility, whereas 23 studies assessed the impact of the recurrence score on chemotherapy decisions or cost-effectiveness.

The analysis of 11 decision-impact studies showed that, based on the recurrence score results in node-positive patients, treatment recommendations were changed in 39% of cases. Additionally, in nine unique global markets, the recurrence score assay was shown to be cost-effective, the authors reported. Dr. Albain noted this may be the first study to look at the economic impact of this assay on cost, specifically for this node-positive subset, and reiterated that a favorable effect was seen across countries.

“This evidence suggests that estrogen receptor–positive patients with few positive nodes and a low recurrence score should have a discussion of the pros and cons of adjuvant chemotherapy, until the results of RxPONDER provide a definitive answer in several years,” the authors stated.

Dr. Albain commented: “The data are very concordant among these seven studies and with the NCCN guidelines, showing that chemotherapy does not appear to benefit some patients with a few positive nodes and low recurrence scores…. The decision-making studies indicated consideration of recurrence score results lowers the use of chemotherapy across trials, in all countries that have used the [recurrence score] assay. For our study team, these date inform our clinical practice and indicate we are giving too much chemotherapy to this low biologic-risk group.” ■

Disclosure: Dr. Albain received research support for the cooperative group project from Genomic Health, Inc., and is on the advisory boards of Myriad and Agendia. Dr. Mamounas is a consultant and on the advisory boards of Genomic Health, and Biotheranostics, and a speaker for Genomic Health.


1. Mamounas E, et al: Chemotherapy decision in patients with node-positive, ER+, early breast cancer in the wake of new ASCO guidelines. 2016 San Antonio Breast Cancer Symposium. Abstract P1-07-02. Presented December 8, 2016.




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