The Breast Cancer Index (BCI) is a significant prognostic factor for the prediction of late disease recurrence

In a presentation given during the 2012 CTRC-AACR San Antonio Breast Cancer Symposium (SABCS), the Breast Cancer Index (BCI) was shown to significantly predict a 10 year distant recurrence rate beyond clinical treatment score (CTS) in estrogen receptor positive (ER+), lymph node negative breast cancer patients. Moreover, in contrast to immunohistochemical-4 (IHC4) and the Oncotype Dx recurrence score (RS), the BCI is also a significant prognostic factor for the prediction of late disease recurrence.
Patients with ER+ early breast cancer have a continuous yearly recurrence rate extending out to 15 years after having received adjuvant endocrine therapy for five years. More than half of the recurrences (i.e. late recurrences) in this group occur beyond five years from diagnosis. As such, residual risk of recurrence remains a substantial concern for ER+ breast cancer patients. Current multi-gene signatures have significant prognostic performance in predicting early recurrence (0-5 years post-diagnosis), but have a limited performance in predicting the risk of late recurrence (> 5 years). BCI is a polymerase-chain reaction (PCR) based assay consisting of two independently developed biomarkers (HOXB1:IL17BR gene expression ratio and the molecular grade index) that stratifies breast cancer patients into three risk groups and has been shown to predict the risk of distant recurrence beyond clinical and pathological parameters. The goal of the presented study was to evaluate whether BCI adds prognostic information to clinical variables in predicting distant recurrences (overall, early and late) in ER+ lymph node negative patients in the TransATAC study. In addition to this, the comparative prognostic performance of BCI with IHC4 and the oncotype Dx RS was determined.

Of the 1,102 tumor specimens assayed, 29 failed quality control and 915 samples were matched for reportable values of BCI, IHC4 and RS. In the presented analyses, only node-negative patients were evaluated (N=665). Similarly to IHC4 and RS, BCI was shown to identify three distinct risk groups for distant metastases over the entire period of 10 years. Furthermore, all three prognostic indices were shown to provide prognostic information beyond CTS for early distant recurrences (> 5 years). However, only BCI was significant beyond CTS for late distant recurrence (5-10 years) (LRχ2: 7.97, p=0.005) vs. RS (LR-χ2: 0.51, p=0.5) and IHC4 (LR-χ2: 1.63, p=0.2).

As such, at the time of diagnosis, BCI is able to distinguish patients at a low risk of early recurrence who are adequately treated with endocrine therapy alone from patients at a high risk of early recurrence who do not benefit adequately from simple endocrine therapy and who should be considered for additional therapy. Furthermore, at the point of 5-year follow-up, BCI can distinguish disease free patients at a low risk of late recurrence that do not need subsequent therapy from patients at a significant risk of late recurrence who should be considered for additional or alternative systemic adjuvant therapy.

In summary, this was the first large-scale clinical study comparing several multi-gene signatures for their prognostic strength to quantify late residual risk of recurrence after endocrine therapy. BCI, unlike IHC4 and RS, was shown to be a significant prognostic factor for late recurrence and enables the assessment of individual recurrence risk for ER+ patients recurrence-free after five years of endocrine therapy.

Reference

D. Sgroi, I. Sestak, J. Cuzick et al.Comparative performance of breast cnacer index (BCI) vs. oncotype DX and IHC4 in the prediction of late recurrence in hormonal receptor-positive lymph node negative breast cancer patients: A transATAC Study. Presented at SABCS 2012; Abstract S1-9.