Concordance among gene expression-based predictors for ER-positive breast cancer treated with adjuvant tamoxifen

• Published in: Annals of oncology Vol. 23; no. 11; pp. 2866 - 2873
• Main Authors: Prat, A., Parker, J.S., Fan, C., Cheang, M.C.U., Miller, L.D., Bergh, J., Chia, S.K.L., Bernard, P.S., Nielsen, T.O., Ellis, M.J., Carey, L.A., Perou, C.M.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-11-2012; Oxford University Press
• Subjects: Adjuvants; Antineoplastic agents; Antineoplastic Agents, Hormonal - therapeutic use; Biological and medical sciences; Biomarkers, Tumor - genetics; breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - mortality; Chemotherapy, Adjuvant; Female; Gene Expression; Gene Expression Profiling; Genomics; Gynecology. Andrology. Obstetrics; Humans; luminal; mammaprint; Mammary gland diseases; Medical sciences; Medicin och hälsovetenskap; oncotype; Original; PAM50; Pharmacology. Drug treatments; Prognosis; Receptors, Estrogen - metabolism; Tamoxifen - therapeutic use; Tumors; mammaprint; PAM50; breast cancer; genomics; luminal; oncotype; Antineoplastic agent; Breast disease; Genomics; Antiestrogen; Breast cancer; Antihormone; Malignant tumor; Gene expression; Tamoxifene; Mammary gland diseases; Selective estrogen receptor modulator; Treatment; Concordance; Genetics; Predictive factor; Genome; Non steroid compound; Cancer
• ISSN: 0923-7534; 1569-8041; 1569-8041
• DOI: 10.1093/annonc/mds080

ER-positive (ER+ ) breast cancer includes all of the intrinsic molecular subtypes, although the luminal A and B subtypes predominate. In this study, we evaluated the ability of six clinically relevant genomic signatures to predict relapse in patients with ER+ tumors treated with adjuvant tamoxifen only.
Four microarray datasets were combined and research-based versions of PAM50 intrinsic subtyping and risk of relapse (PAM50-ROR) score, 21-gene recurrence score (OncotypeDX), Mammaprint, Rotterdam 76 gene, index of sensitivity to endocrine therapy (SET) and an estrogen-induced gene set were evaluated. Distant relapse-free survival (DRFS) was estimated by Kaplan–Meier and log-rank tests, and multivariable analyses were done using Cox regression analysis. Harrell's C-index was also used to estimate performance.
All signatures were prognostic in patients with ER+ node-negative tumors, whereas most were prognostic in ER+ node-positive disease. Among the signatures evaluated, PAM50-ROR, OncotypeDX, Mammaprint and SET were consistently found to be independent predictors of relapse. A combination of all signatures significantly increased the performance prediction. Importantly, low-risk tumors (>90% DRFS at 8.5 years) were identified by the majority of signatures only within node-negative disease, and these tumors were mostly luminal A (78%–100%).
Most established genomic signatures were successful in outcome predictions in ER+ breast cancer and provided statistically independent information. From a clinical perspective, multiple signatures combined together most accurately predicted outcome, but a common finding was that each signature identified a subset of luminal A patients with node-negative disease who might be considered suitable candidates for adjuvant endocrine therapy alone.