The Impact of the 21-gene Recurrence Score Assay on Decision Making About Adjuvant Chemotherapy in Early-stage Estrogen-receptor-positive Breast Cancer in an Oncology Practice With a Unified Treatment Policy

D. B. Geffen; S. Abu-Ghanem; N. Sion-Vardy; R. Braunstein; M. Tokar; S. Ariad; B. Delgado; M. Bayme; M. Koretz


Ann Oncol. 2011;22(11):2381-2386. 

In This Article

Abstract and Introduction


Background: The 21-gene recurrence score (RS) assay has been validated in retrospective studies as prognostic of distant disease recurrence and predictive of the benefit of adjuvant chemotherapy in estrogen-receptor-positive breast cancer (BC). There is limited published data on the impact of the assay on clinical practice, particularly in the context of a single practice with a unified treatment policy.
Patients and methods: Between 2006 and 2009, RS was obtained on 135 patients in a single practice with a uniform treatment policy. Treatment recommendations before and after RS result were analyzed retrospectively. Pre-RS treatment recommendations were based on clinicopathological features and Adjuvant! Online (AO) calculated survival advantage. RS and AO survival advantage for adding chemotherapy were compared for each patient.
Results: The distribution by risk group of RS was low— 49.6%, intermediate—37.8%, and high—12.6%. In 34 patients (25.2%, 95% confidence interval 17.9% to 32.5%), recommendation for chemotherapy was changed after obtaining assay result. Most changes (70.6%) were from chemotherapy to no chemotherapy. The RS correlated poorly with AO predictions.
Conclusion: The 21-gene assay, when applied in a consistent manner in early-stage BC, changes treatment recommendations in one-quarter of patients tested.


Molecular biological techniques have facilitated the development of gene expression tests to individualize prognostic and predictive information for patients with early-stage breast cancer (BC).[1] The 21-gene recurrence score (RS) assay (Oncotype Dx™; Genomic Health, Inc., Redwood City, CA) uses reverse transcriptase–polymerase chain reactions (RT-PCR) to measure RNA extracted from routinely processed paraffin-embedded tumor tissue to quantify expression of 16 cancer-related genes and five reference genes. The assay, developed for use in estrogen-receptor (ER)-positive BC, uses a proprietary algorithm, derived by analysis of tumor tissue from several BC studies, to calculate the RS, expressed as an integer from 0 to 100.[2,3]

The RS was validated in retrospective studies of ER-positive stage I to II axillary node-negative BC as prognostic of distant disease recurrence in tamoxifen-treated patients and predictive of the benefit of adding cyclophosphamide, methotrexate, 5-fluorouracil (CMF) chemotherapy.[4,5] The RS was later validated for postmenopausal patients with axillary node involvement, predicting the benefit of anthracycline-based chemotherapy.[6] The 21-gene test was also shown to be predictive for distant metastases when anastrozole was given instead of tamoxifen.[7]

Palmer et al.[8] of Genomic Health, Inc., reported that during the years 2004 through 2009, >90 000 RS tests were done on patients from the United States (US), while ~2700 specimens from Europe and the Middle East were examined. Despite this extensive use, published data on the impact of the test on clinical practice are limited. In the four published US studies, only 29–89 patients were included with only the three smaller series focusing on a single practice. Treatment recommendations were changed in the four reports because of the RS in 27%–44% of patients.[9–12] Oratz et al.[13] evaluated adjuvant chemotherapy decisions for 160 node-positive patients, each treated by a different oncologist and reported in abstract form that in 45% of patients there was a change in recommendation after knowledge of the RS.

In Israel, the 21-gene test has been funded by one or more of the four nationwide health care organizations (HCOs) since 2006. Klang et al.[14] reported on 368 patients covered by the largest HCO in Israel and found that 40% of patients had their therapeutic plans changed as a result of the RS. Those patients were treated in many different oncology practices with varied criteria for adding adjuvant chemotherapy. We present our experience with the 21-gene RS in a single oncology practice in Israel with a unified treatment policy in 135 patients treated between 2006 and 2009 and evaluate its impact on the selection of adjuvant systemic therapy. We also evaluated whether the RS correlated with the web-based program Adjuvant! Online (Adjuvant, Inc., San Antonio, TX) (AO) predicted mortality reduction by the addition of chemotherapy.[15]


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