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 Cytotoxic agents
Breast Cancer
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Therapy
Biological therapy
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.