Prognostic and Predictive Value of the 21-Gene Recurrence Score Assay in a Randomized Trial of Chemotherapy for Postmenopausal, Node-Positive, Estrogen Receptor-Positive Breast Cancer
By K. Albain, W. Barlow, S. Shak, G. Hortobagyi, R. Livingston, I. Yeh, P. Ravdin, R. Bugarini, Frederick L. Baehner, N. Davidson and 12 more. The Lancet Oncology, 2009
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SUMMARY Background The 21-gene Recurrence Score assay (RS) is prognostic for women with node-negative, estrogen receptor (ER)-positive breast cancer (BC) treated with tamoxifen. A low RS predicts little benefit of chemotherapy. For node-positive BC, we investigated whether RS was prognostic in women treated with tamoxifen alone and whether it identified those who might not benefit from anthracycline-based chemotherapy, despite higher recurrence risks. Methods The phase III trial S8814 for postmenopausal women with node-positive, ER-positive BC showed that CAF chemotherapy prior to tamoxifen (CAF-T) added survival benefit to tamoxifen alone. Optional tumor banking yielded specimens for RS determination by RT-PCR. We evaluated the effect of RS on disease-free survival (DFS) by treatment group (tamoxifen versus CAF-T) using Cox regression adjusting for number of positive nodes. Findings There were 367 specimens (40% of parent trial) with sufficient RNA (tamoxifen, 148; CAF-T, 219). The RS was prognostic in the tamoxifen arm (p=0.006). There was no CAF benefit in the low RS group (logrank p=0.97; HR=1.02, 95% CI (0.54,1.93)), but major DFS improvement for the high RS subset (logrank p=.03; HR=0.59, 95% CI (0.35, 1.01)), adjusting for number of positive nodes. The RS-by-treatment interaction was significant in the first 5 years (p=0.029), with no additional prediction beyond 5 years (p=0.58), though the cumulative benefit remained at 10 years. Results were similar for overall survival and BC-specific survival. Interpretation In this retrospective analysis, the RS is prognostic for tamoxifen-treated patients with positive nodes and predicts significant CAF benefit in tumors with a high RS. A low RS identifies women who may not benefit from anthracycline-based chemotherapy despite positive nodes.
Subfields: Cancer Research, Genetics, Pathology and Forensic Medicine
View Paper: https://www.semanticscholar.org/paper/bc520a09406913237c627097c1c7c9f9614aa1d0
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Citations in the corpus
- Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. (2015, methodology): “Gene expression profiles such as Mammaprint or Oncotype Dx Recurrence Score may be used to gain additional prognostic and/or predictive information to complement pathology assessment and to predict response to adjuvant chemotherapy, in particular in patients with ER-positive early breast cancer [II,”
- Prognostic value of a combined estrogen receptor, progesterone receptor, Ki-67, and human epidermal growth factor receptor 2 immunohistochemical score and comparison with the Genomic Health recurrence score in early breast cancer. (2011, background): “The low- and high-risk categories identified by GHI-RS have been reported to separate women into those who would gain little or substantial benefit from adjuvant chemotherapy, respectively.(13,14) A similar relationship is may exist for the IHC4 score, but direct verification is needed.”
- A New Molecular Predictor of Distant Recurrence in ER-Positive, HER2-Negative Breast Cancer Adds Independent Information to Conventional Clinical Risk Factors (2011, background): “Some tests have been developed in heterogeneous patient cohorts (6-7).”
- Clinical implications of the intrinsic molecular subtypes of breast cancer. (2015, neutral): “mens) [56] and SWOG8814 (FAC regimen) [57].”
- Molecular biology in breast cancer: intrinsic subtypes and signaling pathways. (2012, background): “Also, the information they provide helps oncologists predict more accurately which patients will benefit from chemotherapy, especially when it comes down to ER positive tumors.(48,49) It is argued that the predictive capacity of these platforms narrows down to the fact that they measure proliferatio”