Comparison of gene expression profiles predicting progression in breast cancer patients treated with tamoxifen

M Kok, SC Linn, RK Van Laar, Maurice Jansen, Tineke Berg, LJMJ Delahaye, AM Glas, JL Peterse, M (Michael) Hauptmann, John Foekens, Jan Klijn, LFA Wessels, LJ (Laura) van 't Veer, Els Berns

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Abstract

Background Molecular signatures that predict outcome in tamoxifen treated breast cancer patients have been identified. For the first time, we compared these response profiles in an independent cohort of (neo)adjuvant systemic treatment na < ve breast cancer patients treated with first-line tamoxifen for metastatic disease. Methods From a consecutive series of 246 estrogen receptor (ER) positive primary tumors, gene expression profiling was performed on available frozen tumors using 44K oligoarrays (n = 69). A 78-gene tamoxifen response profile (formerly consisting of 81 cDNA-clones), a 21-gene set (microarray-based Recurrence Score), as well as the HOXB13-IL17BR ratio (Two-Gene-Index, RT-PCR) were analyzed. Performance of signatures in relation to time to progression (TTP) was compared with standard immunohistochemical (IHC) markers: ER, progesterone receptor (PgR) and HER2. Results In univariate analyses, the 78-gene tamoxifen response profile, 21-gene set and HOXB13-IL17BR ratio were all significantly associated with TTP with hazard ratios of 2.2 (95% CI 1.3-3.7, P = 0.005), 2.3 (95% CI 1.3-4.0, P = 0.003) and 4.2 (95% CI 1.4-12.3, P = 0.009), respectively. The concordance among the three classifiers was relatively low, they classified only 45-61% of patients in the same category. In multivariate analyses, the association remained significant for the 78-gene profile and the 21-gene set after adjusting for ER and PgR. Conclusion The 78-gene tamoxifen response profile, the 21-gene set and the HOXB13-IL17BR ratio were all significantly associated with TTP in an independent patient series treated with tamoxifen. The addition of multigene assays to ER (IHC) improves the prediction of outcome in tamoxifen treated patients and deserves incorporation in future clinical studies.
Original languageUndefined/Unknown
Pages (from-to)275-283
Number of pages9
JournalBreast Cancer Research and Treatment
Volume113
Issue number2
Publication statusPublished - 2009

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