Background: The continuous linear Breast Cancer Index (BCI) risk index combines the ratio of genes HOXB13 to IL17BR (H/I) and the molecular grade index (MGI) (Zhang et al, Clinical Cancer Research, 2013). The BCI signature was developed for node-negative breast cancer patients treated with tamoxifen. We examine here whether linear BCI is prognostic for node-positive hormone-receptor positive tamoxifen-treated patients.
Methods: MA.14 randomly assigned 667 hormone positive (HR+), postmenopausal women to 5 years of tamoxifen (TAM) +/- 2 years of octreotide LAR (TAM-OCT). A representative subgroup of 299 patients underwent gene expression profiling by RT-PCR for linear BCI. We performed exploratory analyses restricted to node positive patients. The primary objective was to assess the prognostic effect of BCI on relapse-free survival (RFS). RFS was defined as the time from randomization to the time of recurrence of the primary disease alone, including local and ipsilateral nodal recurrence and metastatic disease, and censoring at longest follow-up or death from another cause. With a median 9.8 years follow-up, the association of BCI with RFS was assessed by multivariate Cox regression including treatment, stratification factors (other than nodal status), and baseline patient and tumor characteristics. Patients were defined to be low risk based on BCI if the adjusted Cox survival was >95%, where adjustment was by trial treatment, stratification factors, and baseline patient and tumor characteristics, including IGF-1, IGFBP-3, and C-peptide.
Results: 292 of 299 patient samples passed internal analytical quality control; 116 node positive ER+ve patients had 34 (29.3%) relapses, with adjusted Cox survival at 9.6 years of 87.8%. Fifty-two of the 116 patients (45%) did not receive adjuvant chemotherapy, and experienced 11 (21%) RFS events. In the 116 patients, higher continuous BCI value was associated with shorter RFS (p=0.002): hazard ratio (HR) 1.49 (95% CI 1.16-1.91). Smaller pathologic T had significantly (p=0.03) better RFS HR=0.39, (95%CI 0.17-0.90). With MA.14 patient mean BCI of 5.09532, Cox survival at 4.1 years was 95.2%; 17/34 (50%) who recurred had failed by this time.
Discussion: In this subgroup analysis, we found that BCI and tumor size were significant prognostic factors for node-positive hormone-receptor positive patients who were treated with tamoxifen.
Citation Format: Dennis Sgroi, Paul Goss, Judy-Anne Chapman, Elizabeth Richardson, Shemeica Binns, Yi Zhang, Cathy Schnabel, Mark Erlander, Kathy Pritchard, Lei Han, Lois Sheperd, Michael Pollack. Prognostic significance of breast cancer index (BCI) in node-positive hormone receptor positive early breast cancer: NCIC CTG MA.14 [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-01-10.