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 naïve 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.
BACKGROUND: Molecular signatures that predict outcome in tamoxifen treated breast cancerpatients have been identified. For the first time, we compared these response profiles in an independent cohort of (neo)adjuvant systemic treatment naïve breast cancerpatients 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.
Authors: Thomas P Ahern; Deirdre P Cronin-Fenton; Timothy L Lash; Henrik Toft Sørensen; Anne Gulbech Ording; Stephen J Hamilton-Dutoit; Ylva Hellberg Journal: Acta Oncol Date: 2016-04-08 Impact factor: 4.089
Authors: Ines Barone; Lauren Brusco; Guowei Gu; Jennifer Selever; Amanda Beyer; Kyle R Covington; Anna Tsimelzon; Tao Wang; Susan G Hilsenbeck; Gary C Chamness; Sebastiano Andò; Suzanne A W Fuqua Journal: J Natl Cancer Inst Date: 2011-03-29 Impact factor: 13.506
Authors: Yinghui Zhang; Lynn Wester; Jichao He; Tamar Geiger; Marja Moerkens; Ram Siddappa; Jean A Helmijr; Mieke M Timmermans; Maxime P Look; Caroline H M van Deurzen; John W M Martens; Chantal Pont; Marjo de Graauw; Erik H J Danen; Els M J J Berns; John H N Meerman; Maurice P H M Jansen; Bob van de Water Journal: Oncogene Date: 2018-01-22 Impact factor: 9.867
Authors: Lorenza Mittempergher; Mahasti Saghatchian; Denise M Wolf; Stefan Michiels; Sander Canisius; Philippe Dessen; Suzette Delaloge; Vladimir Lazar; Stephen C Benz; Thomas Tursz; René Bernards; Laura J van't Veer Journal: Mol Oncol Date: 2013-07-17 Impact factor: 6.603