| مستخلص: |
Background: Several proliferation-related gene signatures have been proposed to aid breast cancer management by providing better prognostic and therapy predictive information on a patient-by-patient basis. It is unclear however, whether a less demanding assessment of cell division rate (as determined by Ki67 expression) can function in place of gene profiling. Methods: Agreement between literature-, distribution-based, as well as signature-derived threshold values for Ki67, relative to the genomic grade index (GGI), the 70-gene signature, the p53 signature, the recurrence score (RS), and the molecular subtype models of Sorlie, Hu, and Parker was investigated in a representative set of 253 breast cancers with 25 years follow up. Relevance for breast cancer specific survival was assessed for contrast groups, and in uni- and multivariate Cox models. Results: Our broad approach identified Ki67 cutoffs in the range of 10%-20%. With optimum signature-reproducing cutoffs, similarity in classification of individual tumors was high for GGI (81%), the 70-gene (78%), and the p53 (82%) signatures, but lower for the recurrence score (68%), Sorlie (68%), Parker (67%) and Hu (68%) signatures. Consistent with strong agreement, no prognostic superiority was noted for Ki67 vs. the binary GGI, 70-gene and p53 signatures respectively, in multivariate analyses. In contrast, Ki67-independent prognostic capacity could be demonstrated for RS and molecular subtypes according to Sorlie, Parker and Hu (Table 1). Conclusions: The added prognostic value of binary proliferation-related gene signatures appears limited for Ki67-assessed breast cancers. More complex, multi-level descriptions seem to have a greater potential in pinpointing the outcome heterogeneity in breast cancer. We aim to validate our findings in a second cohort of 159 breast cancer patients with over 15 years of clinical follow up. [ABSTRACT FROM AUTHOR] |
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