Assessment of the prognostic and predictive utility of the Breast Cancer Index (BCI): an NCIC CTG MA.14 study

Dennis C Sgroi, Judy-Anne W Chapman, T Badovinac-Crnjevic, Elizabeth Zarella, Shemeica Binns, Yi Zhang, Catherine A Schnabel, Mark G Erlander, Kathleen I Pritchard, Lei Han, Lois E Shepherd, Paul E Goss, Michael Pollak, Dennis C Sgroi, Judy-Anne W Chapman, T Badovinac-Crnjevic, Elizabeth Zarella, Shemeica Binns, Yi Zhang, Catherine A Schnabel, Mark G Erlander, Kathleen I Pritchard, Lei Han, Lois E Shepherd, Paul E Goss, Michael Pollak

Abstract

Background: Biomarkers that can be used to accurately assess the residual risk of disease recurrence in women with hormone receptor-positive breast cancer are clinically valuable. We evaluated the prognostic value of the Breast Cancer Index (BCI), a continuous risk index based on a combination of HOXB13:IL17BR and molecular grade index, in women with early breast cancer treated with either tamoxifen alone or tamoxifen plus octreotide in the NCIC MA.14 phase III clinical trial (ClinicalTrials.gov Identifier NCT00002864; registered 1 November 1999).

Methods: Gene expression analysis of BCI by real-time polymerase chain reaction was performed blinded to outcome on RNA extracted from archived formalin-fixed, paraffin-embedded tumor samples of 299 patients with both lymph node-negative (LN-) and lymph node-positive (LN+) disease enrolled in the MA.14 trial. Our primary objective was to determine the prognostic performance of BCI based on relapse-free survival (RFS). MA.14 patients experienced similar RFS on both treatment arms. Association of gene expression data with RFS was evaluated in univariate analysis with a stratified log-rank test statistic, depicted with a Kaplan-Meier plot and an adjusted Cox survivor plot. In the multivariate assessment, we used stratified Cox regression. The prognostic performance of an emerging, optimized linear BCI model was also assessed in a post hoc analysis.

Results: Of 299 samples, 292 were assessed successfully for BCI for 146 patients accrued in each MA.14 treatment arm. BCI risk groups had a significant univariate association with RFS (stratified log-rank p = 0.005, unstratified log-rank p = 0.007). Adjusted 10-year RFS in BCI low-, intermediate-, and high-risk groups was 87.5 %, 83.9 %, and 74.7 %, respectively. BCI had a significant prognostic effect [hazard ratio (HR) 2.34, 95 % confidence interval (CI) 1.33-4.11; p = 0.004], although not a predictive effect, on RFS in stratified multivariate analysis, adjusted for pathological tumor stage (HR 2.22, 95 % CI 1.22-4.07; p = 0.01). In the post hoc multivariate analysis, higher linear BCI was associated with shorter RFS (p = 0.002).

Conclusions: BCI had a strong prognostic effect on RFS in patients with early-stage breast cancer treated with tamoxifen alone or with tamoxifen and octreotide. BCI was prognostic in both LN- and LN+ patients. This retrospective study is an independent validation of the prognostic performance of BCI in a prospective trial.

Figures

Fig. 1
Fig. 1
Risk-free survival Kaplan-Meier plot of Breast Cancer Index (BCI). CTG Clinical Trials Group
Fig. 2
Fig. 2
Risk-free survival adjusted Cox survivor plot by Breast Cancer Index (BCI), adjustments by treatment, MA.14 stratification factors, and pathologic tumor stage. CTG Clinical Trials Group

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Source: PubMed

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