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 (P interaction = 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 (P interaction = 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.
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Authors | Mitch Dowsett, Ivana Sestak, Richard Buus, Elena Lopez-Knowles, Elizabeth Mallon, Anthony Howell, John F Forbes, Aman Buzdar, Jack Cuzick |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 21
Issue 12
Pg. 2763-70
(Jun 15 2015)
ISSN: 1557-3265 [Electronic] United States |
PMID | 26078431
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | ©2015 American Association for Cancer Research. |
Chemical References |
- RNA, Messenger
- Receptors, Estrogen
- Receptor, ErbB-2
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Topics |
- Breast Neoplasms
(epidemiology, genetics, pathology)
- Female
- Follow-Up Studies
- Gene Expression
- Humans
- Neoplasm Recurrence, Local
- RNA, Messenger
(genetics)
- Receptor, ErbB-2
(genetics)
- Receptors, Estrogen
(genetics, metabolism)
- Time Factors
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