Association between standard clinical and pathologic characteristics and the 21‐gene recurrence score in breast cancer patients

Abstract

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.

Expression of Forkhead-box protein A1, a marker of luminal A type breast cancer, parallels low Oncotype DX 21-gene recurrence scores

“…We also observed similar findings in the studies evaluating the influence of Oncotype DX recurrence score on decision making and its association with clinicopathologic features. [24][25][26][27] Thus, our study likely represents a more 'real-life' distribution of Oncotype DX risk categories in patients with early-stage ER-positive disease.…”

“…Owing to these concerns, several investigators have attempted to use clinicopathologic features to predict the recurrence score. In a population-based cohort of 300 early-stage breast cancer patients, Wolf et al 24 determined that neither standard clinicopathologic features nor commonly used clinical guidelines reliably predicted the recurrence score. Another study by Flanagan et al 25 suggested that the recurrence score correlated with histopathologic variables such as tubule formation, nuclear grade, mitotic count, ER status, PR status, and Her2/neu status.…”

A mitotically active, cellular tumor stroma and/or inflammatory cells associated with tumor cells may contribute to intermediate or high Oncotype DX Recurrence Scores in low-grade invasive breast carcinomas

“…Although there have been substantial efforts to clinically validate the ability of Recurrence Score to predict outcome and likelihood of response to therapy in large series of patients with early stage, ER-positive breast cancer, there are little data to show that the Recurrence Score is in fact reflective of the recurrence risk and/ or likelihood of response to chemotherapy in an individual patient. Associations between various clinicopathological tumor features and Recurrence Score have been examined in a limited number of studies, 44,[62][63][64] some even suggesting that Recurrence Score can be estimated based on histopathological features, 44,62,63 but little attention has been paid to the 'discrepant' cases. Similar to our experience, Allison et al 44 have also observed that a significant number of breast cancers that were expected to receive a low Recurrence Score based on clinicopathological features resulted in intermediate or high Recurrence Score, noting that little has been done to investigate the possibility that some cases may have a falsely low or high Recurrence Score when compared with what would be expected based on routine pathological parameters.…”

Distinguishing luminal breast cancer subtypes by Ki67, progesterone receptor or TP53 status provides prognostic information

“…For example, higher Oncotype DX s recurrence scores have been shown to correlate with high grade, PR negativity, and HER2 positivity. 8,16,17,30 Furthermore, an immunohistochemical panel of ER, PR, HER2, and Ki67 in conjunction with standard clinicopathological parameters (IHC4 score) has been shown to provide similar prognostic information to the recurrence score in hormone receptor-positive patients treated with endocrine therapy. 31 Integration of such an immunohistochemical panel into routine practice would merely require the addition of Ki67 to the pathologist's workload.…”

“…TP53 positivity in breast cancer is significantly associated with high histological grade and high proliferation index, 12,15 and consequently could potentially be substituted for Ki67 in an immunohistochemical-based classifier. Progesterone receptor (PR) negativity correlates with a high Oncotype DX s recurrence score in keeping with a luminal B genotype, 8,16,17 and therefore represents another possible surrogate marker for Ki67 in segregating luminal cancers into low-and high-risk categories.…”