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. 

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To the best of our knowledge, this report describes the largest series of patients tested for the 21-gene RS in a single practice with a standard treatment policy. The distribution of RS by risk group in our series is very similar to that reported by Genomic Health from specimens sent from the US and Europe/Middle East as well as that reported in Japanese BC patients.[8,17] This information suggests that the 16 cancer-related genes measured in the RS are expressed to a similar degree in most populations with BC.

Treatment recommendations were changed in 34 (25%) patients, with 24 patients changed to endocrine therapy only and 10 patients to adding chemotherapy to endocrine therapy. PR-negative patients as a group, received a greater proportion of recommendations for chemotherapy pre-RS and, had a higher median RS than PR positive patients. A surprising number of patients, 16 (11.9%), chose not to accept the post-RS recommendations, 2 (1.5%) requesting chemotherapy after we recommended endocrine therapy alone and 14 (10.4%) patients refusing recommended chemotherapy. The age range of patients refusing chemotherapy despite RS was 36–73 years with a median of 56. Two other studies show a discrepancy between recommendations for receiving chemotherapy after obtaining RS and the number of patients actually receiving chemotherapy, with 13% and 33% of patients who were recommended for chemotherapy not actually receiving it in the Lo et al.[9] and the Oratz et al.[12] reports, respectively. Patients' understanding of the RS needs to be further investigated.

AO has been validated as an accurate prognostic indicator.[18] Neither others nor we have seen a close correlation between the RS and the AO 10-year survival prediction, supporting the complementary nature of these tools.[12,19,20] Alternatively, there may be confounding factors in the existing studies that are as yet not identified.

The dearth of high-grade patients—RS was obtained for only 7 high-grade patients—was probably because of physician preference as earlier noted to continue treating high-grade patients with chemotherapy. During the study period, our practice saw ~120 patients with high-grade early-stage BC. Approximately 90% received chemotherapy. The lack of correlation between histological grade and recommendation for change in therapy may be a reflection of the difficulty in reproducing assignment of grade as opposed to the more quantitative results of RT-PCR measurements comprising the basis of the RS.[21]

The other predictive molecular test in use is the 70-gene signature (Mammaprint™; Agendia, Amsterdam, the Netherlands) based on microarray techniques. It requires the use of fresh tissue and is useful for ER negative as well as positive tumors. A prospective community based study showed a 27%–39% discordance between prognosis according to the gene test and according to various clinicopathological criteria.[22]

Limitations of our study include the nonrandom and nonuniform selection of patients for testing. We tended not to test high-grade patients for whom we usually recommended chemotherapy. On the other hand, the tested patients were representative of those for whom clinicians have the most difficulty in deciding on the proper course of adjuvant chemotherapy in BC. There were insufficient patients with high-grade tumors or positive nodes to draw conclusions about the relationship of the RS to grade or nodal status. As more experience with the test is reported, its use will probably expand in those groups of patients.

The major strength of our study is the uniform policy of treatment. The physicians in the practice all used the same approach for deciding on chemotherapy before receiving the RS report, and used the same RS cut-off points for changing therapy decisions. There were isolated deviations from set policies. We are now using the 21-gene assay for ER-positive, HER2-negative (PR negative and positive) axillary node-negative patients of all grades, and in postmenopausal patients, with up to three involved axillary nodes.

In conclusion, the 21-gene RS reduced the number of patients for whom chemotherapy was recommended for the adjuvant treatment of ER-positive BC by 22%. While both the 21-gene test and the 70-gene signature are the subjects of ongoing prospective validation trials, clinical guidelines for the treatment of early BC already encourage their use.[5,23–25] Our experience suggests that the use of the 21-gene RS facilitates routine molecular-based personalized medicine for ER-positive early-stage BC.


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