Prognostic utility of HOXB13 : IL17BR and molecular grade index in early-stage breast cancer patients from the Stockholm trial

Background: A dichotomous index combining two gene expression assays, HOXB13:IL17BR (H:I) and molecular grade index (MGI), was developed to assess risk of recurrence in breast cancer patients. The study objective was to demonstrate the prognostic utility of the combined index in early-stage breast cancer. Methods: In a blinded retrospective analysis of 588 ER-positive tamoxifen-treated and untreated breast cancer patients from the randomized prospective Stockholm trial, H:I and MGI were measured using real-time RT-PCR. Association with patient outcome was evaluated by Kaplan-Meier analysis and Cox proportional hazard regression. A continuous risk index was developed using Cox modeling. Results: The dichotomous H:I+MGI was significantly associated with distant recurrence and breast cancer death. The >50% of tamoxifen-treated patients categorized as low-risk had <3% 10-year distant recurrence risk. A continuous risk model (Breast Cancer Index (BCI)) was developed with the tamoxifen-treated group and the prognostic performance tested in the untreated group was 53% of patients categorized as low-risk with an 8.3% 10-year distant recurrence risk. Conclusion: Retrospective analysis of this randomized, prospective trial cohort validated the prognostic utility of H:I+MGI and was used to develop and test a continuous risk model that enables prediction of distant recurrence risk at the patient level.Original Publication:Piiha-Lotta Jerevall, Xiai-Jun Ma, Hongying Li, Ranelle Salunga, Nicole C. Kesty, Mark G. Erlander, Dennis Sgroi, Birgitta Holmlund, Lambert Skoog, Tommy Fornander, Bo Nordenskjöld and Olle Stål, Prognostic utility of HOXB13:IL17BR and Molecular Grade Index in early-stage breast cancer patients from the Stockholm trial, 2011, British Journal of Cancer, (104), 11, 1762-1769.http://dx.doi.org/10.1038/bjc.2011.145Copyright: Nature Publishing Grouphttp://npg.nature.com

Markers for the identification of late breast cancer recurrence

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Progression of Early Breast Cancer to an Invasive Phenotype

Histological and molecular evidence has led to a model of breast cancer progression in which cells from the terminal duct lobular unit give rise to atypical ductal hyperplasia or atypical lobular hyperplasia, which can progress to ductal carcinoma in situ or lobular carcinoma in situ, and eventually to invasive ductal carcinoma or invasive lobular carcinoma respectively. This review will present a histomorphological and epidemiological overview of the pre-invasive stages of breast cancer progression. As there is mounting evidence that these stages are likely rough phenotypes of underlying molecular changes, current knowledge regarding changes in genetic and epigenetic features of breast cancer progression will also be discussed. Microarray and CGH-based studies will be described, which suggest that low- and high-grade breast cancers can arise from normal terminal ducts through two distinct molecular pathways. Various in vitro and in vivo models used to study the cellular and molecular changes involved in early breast cancer progression will be presented. Lastly, the specific transition from pre-invasive to invasive breast cancer will be addressed, including possible molecular predictors of the invasive phenotype and a contemporary view highlighting the involvement of the tumor microenvironment during the transition to invasive disease