177P - Recurrence score and quantitative ER expression predicts late distant recurrence risk in ER+ BC after five years of tamoxifen

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Early Stage
Biomarkers
Presenter Terry Mamounas
Citation Annals of Oncology (2014) 25 (suppl_4): iv58-iv84. 10.1093/annonc/mdu326
Authors T. Mamounas1, N. Wolmark2, F. Baehner3, S. Butler4, G. Tang5, F. Jamshidian4, A. Sing6, S. Shak7, S. Paik2
  • 1Breast Care Center, University of Florida Health Cancer Center at Orlando Health, 32806 - Orlando/US
  • 2Nsabp, National Surgical Adjuvant Breast and Bowel Project, 15212 - Pittsburgh/US
  • 3Pathology, Genomic Health, Inc., 94063 - Redwood City/US
  • 4Biostatistics, Genomic Health, Inc., 94063 - Redwood City/US
  • 5Biostatistics, NSABP, 15212 - Pittsburgh/US
  • 6Medical Affairs, Genomic Health, Inc., 94063 - Redwood City/US
  • 7Oncology Development, Genomic Health, Inc., 94063 - Redwood City/US

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.

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.