177P - Recurrence Score and Quantitative Er Expression Predicts Late Distant Recurrence Risk in Er+ Bc After Five Years of Tamoxifen

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ABSTRACT Aim: Identification of molecular determinants predicting late recurrence (>5 yrs) in stage I and II breast cancer has become clinically important in light of data demonstrating a benefit for 10 yrs of tamoxifen administration. Since the 21-gene Recurrence Score (RS) is commonly utilized in early stage BC, we wished to determine its utility in predicting distant recurrences beyond 5 yrs as a function of quantitative ER expression. Methods: The 21-gene RS was assessed in 1065 chemo and tam-treated, ER + , node-positive pts from NSABP B-28 and 668 tam-treated, ER + , node-negative pts from NSABP B-14. Cox PH models, KM estimates and log rank statistics were used to assess the association of the RS with risk of DR by quantitative ER expression, using the 21-gene assay, in pts event-free after 5 yrs. We established an ER cut-point (high vs low) in B-28, and tested the cut-point in B-14, formally evaluating the interaction of RS and ER. Results: Median follow-up was 11.2 yrs (B-28) and 14.5 yrs (B-14). 832 B-28 pts and 564 B-14 pts were DR-free after 5 yrs. A reference normalized ER cut-point of 9.1 CT was established in B-28 based on the association of the RS with DR after 5 yrs. Of the event-free pts at 5 yrs, 68% in B-28 and 88% in B-14 had ER > 9.1. In B-28 the RS result was strongly associated with DR after 5 yrs in the higher ER expressing pts (log rank P = 0.001), but not in the lower ER expressing pts (log rank P = 0.87). It was confirmed in the B-14 data that RS was associated with DR after 5 yrs in higher ER pts (Table) but not in the lower ER pts (interaction P = 0.03). The association of RS risk groups within clinicopathologic subgroups for the higher ER patients still at risk at 5 years will also be presented. Table 177P . DR Risk after 5 yrs in B-14 by RS Risk Group for pts with ER > 9.1 C T % DR KM estimate (95% CI) RS Risk Group N(%) pts 5 to 10 yrs (%) 5 to 15 yrs % Low 289 (58%) 4.7 (2.8 – 8.0) 6.8 (4.4 – 10.6) Intermediate 111 (22%) 4.1 (1.6 – 10.6) 11.2 (6.2 – 19.9) High 97 (20%) 12.6 (7.4 – 21.2) 16.4 (10.2 – 25.7) Log rank P = 0.01 Conclusions: For late recurrences (beyond 5 yrs), the RS is strongly prognostic in pts with higher quantitative ER expression (>9.1). The findings suggest that extending tamoxifen beyond 5 yrs may be most beneficial in pts with high (and intermediate) RS with higher quantitative ER expression and of limited benefit in pts with a low RS (>50% of population under study). Disclosure: F. Baehner, S. Butler, F. Jamshidian and A. Sing have decalred: I am an employee of Genomic Health, Inc. I receive a salary and company stock. S. Shak: I am an employee of Genomic Health, Inc and I serve in a leadership position. I receive a salary and I have company stock.All other authors have declared no conflicts of interest.