Estrogen receptor expression in 21-Gene recurrence score predicts increased late recurrence for estrogen-positive/HER2-Negative breast cancer

Mitch Dowsett, Ivana Sestak, Richard Buus, Elena Lopez-Knowles, Elizabeth Mallon, Anthony Howell, John F. Forbes, Aman Buzdar, Jack Cuzick

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Purpose: To identify the individual genes or gene modules that lead to the OncoptypeDx 21-gene recurrence score's reduced performance after 5 years and thereby identify indices of residual risk that may guide selection of patients for extended adjuvant therapy. Experimental Design: We conducted a retrospective assessment of the relationship between (i) the individual genes and gene modules of the Recurrence Score and (ii) early (0-5 years) and late (5-10 years) recurrence rates in 1,125 postmenopausal patients with primary estrogen receptor-positive breast cancer treated with anastrozole or tamoxifen in the Arimidex, Tamoxifen, Alone or Combined (ATAC) randomized clinical trial. Results: In the HER2-negative population (n = 1,009), estimates of recurrence risk were similar between years 0-5 and 5-10 for proliferation and invasion modules but markedly different for the estrogen module and genes within it (all split at the median): for low estrogen module, annual recurrence rates were similar across the two time windows (2.06% vs. 2.46%, respectively); for high estrogen module, annual rates were 1.14% versus 2.72%, respectively (Pinteraction = 0.004). Estrogen receptor transcript levels showed inverse prediction across the time windows: HR, 0.88 (0.73-1.07) and 1.19 (0.99-1.43), respectively (Pinteraction = 0.03). Similar time-, module-, and estrogen-dependent relationships were seen for distant recurrence. Conclusions: Patients with tumors with high estrogen receptor transcript levels benefit most from 5 years' endocrine therapy but show increased recurrence rates after 5 years and may benefit from extended therapy. Improved prognostic profiles may be created by considering period of treatment and follow-up time.

Original languageEnglish (US)
Pages (from-to)2763-2770
Number of pages8
JournalClinical Cancer Research
Volume21
Issue number12
DOIs
StatePublished - Jun 15 2015

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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