BackgroundBiomarkers 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).MethodsGene 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.ResultsOf 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).ConclusionsBCI 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-015-0660-6) contains supplementary material, which is available to authorized users.

LBA1003 Background: Randomized trials have demonstrated that locoregional radiation after mastectomy reduces locoregional recurrence and improves overall survival (OS) in women with node positive breast cancer treated with adjuvant systemic therapy. MA.20 evaluated the addition of regional nodal irradiation (RNI) to whole breast irradiation (WBI) following breast conserving surgery (BCS). Methods: Women with high risk node-negative or node-positive breast cancer treated with BCS and adjuvant chemotherapy and/or endocrine therapy were stratified by positive nodes, axillary nodes removed, chemo- and endocrine therapy and randomized to WBI (50Gy in 25 fractions +/- boost irradiation) or WBI plus RNI (45Gy in 25 fractions) to the internal mammary, supraclavicular, and high axillary lymph nodes. The primary outcome was OS. The Data Safety Monitoring Committee approved the analysis plan for the protocol specified interim analysis of relapse patterns, survival and toxicity at 5 years. Upon review of the data, they recommended release of the results. Results: Between March 2000 to March 2007, 1,832 women were randomly assigned to WBI+RNI (916) or WBI (916). Median follow-up was 62 months. Characteristics of the study population were: mean age, 53.3 years; node negative, 10%; 1-3 positive nodes, 85%; > 4 positive nodes, 5%; adjuvant chemotherapy, 91%; and adjuvant endocrine therapy, 71%. WBI+RNI in comparison to WBI alone was associated with an improvement in isolated locoregional disease free survival (DFS; HR=.59, p=.02, 5 year risk: 96.8% and 94.5% respectively), distant DFS (HR=.64, p=.002, 5 year risk: 92.4% and 87.0% respectively), DFS (HR=.68, p=.003, 5 year risk: 89.7% and 84.0% respectively) and OS (HR=.76, p=.07, 5 year risk: 92.3% and 90.7% respectively). WBI+RNI in comparison to WBI was associated with an increase in grade 2 or greater pneumonitis (1.3% and 0.2% respectively, p=.01), and lymphedema (7.3% and 4.1% respectively, p=.004). Conclusions: The majority of women with node positive breast cancer are now managed by BCS followed by WBI and adjuvant systemic therapy. Results from MA.20 demonstrate that additional RNI reduces the risk of locoregional and distant recurrence, and improves DFS with a trend in improved OS.