Abstract

Abstract Background: Molecular genomic profiling currently plays a major role in treatment decisions for breast cancer patients. The 21-gene signature (Oncotype DX® [ODX]) is one of the most well-validated assays. Herein we evaluated the associations between high Recurrence Score (RS) measured by the ODX and pathological factors. Methods: From October 2007 to October 2010, the ODX assay was performed for 139 hormone-receptor–positive invasive breast cancer patients at single institution. Correlations between the RS and the following pathological factors were analyzed: tumor size (T), lymph node metastasis (N), nuclear atypia (NA), mitotic counts (MC), nuclear grade (NG), lymphatic and vascular invasion (LI and VI), estrogen receptor (ER), progesterone receptor (PgR), HER2, and Ki-67. Expression of ER, PgR, HER2, and Ki-67 was examined by immunohistochemistry. The Ki-67 labeling index was automatically counted with an Ariol-SL50 instrument (APPLIED IMAGING). The other pathological factors were estimated under the supervision of one experienced pathologist. Spearman rank correlation coefficients were calculated for the analyses. When the r was >0.4 or <–0.4 for two factors, they were determined to be well correlated. Results: Of 139 patients, the ODX assay revealed 68 (49%) low RS cases, 52 (37%) intermediate RS cases, and 19 (14%) high RS cases. Moderate positive or negative correlations were noted between the RS and PgR (r = −0.53), the RS and Ki-67 (r = 0.42), and the RS and NG (r = 0.41). No patients had high RS with PgR (3+) or NG1. The rate of high RS with Ki-67 (<20%) was one patient (2%). The number of cases who did not show PgR (3+) or NG1 or Ki-67 (<20%) was only 34 (25%). Among high RS cases, the correlation between PgR (0) and NG3 was 83%, the correlation between PgR (0) and NG2 was 75%, and the correlation between PgR (1+) and NG3 was 75%. The rate of high RS with PgR (0) and Ki-67 (≥20%) was 70%, that of PgR (1+) and Ki-67 (≥20%) was 58%, and that of PgR (2+) and Ki-67 (≥20%) was 21%. Correlations with T, N, NA, MC, LI, VI, ER, and HER2 were smaller (r ranging from −0.33 to 0.38). Conclusion: This study demonstrated that PgR, NG, and Ki-67 tend to be strongly correlated with the RS. Judging from PgR (3+), NG1, and Ki-67 (≥20%), we could select the patients who were proposed to perform the ODX. Among these factors, the correlation with PgR was particularly robust. PgR expression is a known marker of a functional ER and represents ER activity. In addition, the absence of PgR may reflect hyperactive cross-talk between ER and growth factor signaling pathways. We consider that these mechanisms could enhance the value of PgR in predicting the RS. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-07-38.

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