- BACKGROUND. The 21-gene recurrence score (RS) assay has been reported to accurately predict the risk of disease recurrence and chemotherapy benefit in women with estrogen receptor (ER)-positive, lymph node (LN)-negative breast cancer who are treated with tamoxifen. To the authors' knowledge, the association between the RS and clinicopathologic characteristics has been studied in randomized and case-control trials, but not in the general population. METHODS. The authors analyzed the correlation between clinicopathologic breast cancer characteristics and RS among 300 consecutive Israeli patients who were referred to undergo the test between October 2004 and October 2006. RESULTS. Low, intermediate, and high RS were noted in 109 patients (36%), 134 patients (45%), and 57 patients (19%), respectively. The median age of the patients was 54 years and the median tumor size was 1.6 cm. High tumor grade, low progesterone receptor expression, infiltrating ductal histology, and high HER-2 expression were found to be associated with a high RS, whereas patient age, tumor size, ER expression, and lymph node micrometastasis were found to correlate poorly with the RS. The ability of any of these variables, either alone or in combination, to predict the RS was limited. Similarly, neither commonly used guidelines nor the Adjuvant! Online software were found to be able to predict the RS. CONCLUSIONS. The results of the current study suggest that neither standard clinicopathologic features nor commonly used assessment tools can reliably predict the RS among referred breast cancer patients compared with a clinical trial population. These data also may indicate the need for additional studies regarding the role of the RS among certain subsets of breast cancer patients, including those with noninfiltrating ductal carcinoma histology and the presence of lymph node micrometastasis. Cancer 2008. © 2007 American Cancer Society.