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

Abstract

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 randomised 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 modelling.Results:The dichotomous H : I+MGI was significantly associated with distant recurrence and breast cancer death. The >50% of tamoxifen-treated patients categorised 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 categorised as low risk with an 8.3% 10-year distant recurrence risk.Conclusion:Retrospective analysis of this randomised, 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.

Biological subtypes of breast cancer: Prognostic and therapeutic implications

“…This assay has been developed from the combination of two indices: the ratio of HOXB13/IL17BR genes, which predicts distant recurrence in ER-positive patients treated with tamoxifen, and a proliferation related five gene molecular grade index, which discriminates grade 1 from grade 3 disease. The test is based on qRT-PCR using RNA from paraffin embedded tissues [75,76] . The biological roles of the genes included in most of these tests are not completely understood and it is often unclear which clinical or tumor characteristics are being measured.…”

Breast Cancer Index Identifies Early-Stage Estrogen Receptor–Positive Breast Cancer Patients at Risk for Early- and Late-Distant Recurrence

“…Given the persistent risk of recurrence beyond 5 years, there is a significant clinical unmet need for biomarkers that accurately assess the risk of recurrence across the full disease time horizon. Breast Cancer Index (BCI) is a gene expression-based biomarker that was developed using a cohort of tamoxifen-treated patients from the randomized prospective Stockholm trial and has been shown to provide an individual risk of distant breast cancer recurrence based on a continuous risk model (9). BCI was developed through the algorithmic combination of 2 previously described biomarkers, HOXB13:IL17BR ratio (H/I) and the Molecular Grade Index (MGI), and provided superior prognostic performance than either biomarker alone (10)(11)(12).…”

Hormonal therapy in breast cancer: A model disease for the personalization of cancer care

“…Examples include the use of two predictive gene expression indices , the HOXB13: IL17BR (H:I) and the molecular grade index (MGI) which has been found to correlate with prognosis in ERþ patients with early stage breast cancer (Jerevall et al, 2011;Ma et al, 2004). The Mammastrat test has identified additional markers predictive of outcome which can be assessed using immunohistochemistry, and therefore has the potential to be more broadly performed in hospital laboratories (Ross et al, 2008;Bartlett et al, 2010) At this time; none of these assays is clearly superior over the other by any measure evaluated including cost-effectiveness (Retel et al, 2011).…”