Abstract S1-9: Comparative Performance of Breast Cancer 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
Authors: Sgroi DC , Sestak I , Cuzick J , Zhang Y , Schnabel CA , Erlander MG , Goss PE , Dowsett M 
Published: August 2014

Abstract
Background: Patients with estrogen receptor positive (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 will occur beyond five years from diagnosis. Thus, 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), however, such signatures have limited performance in predicting the risk of late recurrence (&gt; 5 years) (Albain et al. Lancet Oncol 2010; 11: 55–65; Buyse et al. JNCI 2006; 98: 1183–1192). The comparative prognostic performance of Breast Cancer Index (BCI), Recurrence Score (RS) and IHC4 for predicting early and late recurrence was examined in the translational arm of Arimidex, Tamoxifen, Alone or in Combination trial (TransATAC).
Methods: RNA extracted from 1102 formalin-fixed paraffin-embedded blocks of primary tumor samples previously collected for the TransATAC study was used to perform real-time RT-PCR for BCI analyses. BCI was calculated and risk groups were determined using pre-specified cut points. RS and IHC4 values were previously generated. The prognostic value of each signature beyond standard clinical variables (Clinical Treatment Score (CTS) was assessed using likelihood ratio chi-square (LR-χ2) and calculated by Cox proportional hazards models. Prognostic evaluation for early recurrences (0–5 years) was performed by censoring survival time to 5 years, and for late recurrences (5–10 years) by analyzing those patients who had remained recurrence-free for at least 5 years. Clinical endpoints examined were distant recurrence, any recurrence, breast cancer death and overall survival.
Results: Of 1102 tumor specimens assayed, 29 failed quality control and 915 samples were matched for reportable values of BCI, IHC4 and RS. Here, only node-negative patients were evaluated (N = 665). All 3 signatures had significant prognostic performance for early distant recurrence (0–5 years), and overall (0–10 years) each provided prognostic information beyond CTS with LR-χ2 values of 22.7, 22.9 and 13.8 for BCI, IHC4 and RS, respectively. Notably, only BCI was significant beyond CTS for late distant recurrence (5–10 years) (LR-χ2: 7.97, p = 0.005) versus RS (LR-χ2: 0.51, p = 0.5) and IHC4 (LR-χ2: 1.63, p = 0.2). Similar comparative results of BCI, RS and IHC4 for late recurrence were observed for the other clinical endpoints.
Discussion: This is the first large-scale clinical study to compare several multi-gene signatures for their prognostic strength to quantify late residual risk of recurrence after endocrine therapy. BCI, unlike IHC4 and RS, is a significant prognostic factor for late recurrence and enables the assessment of individual recurrence risk for ER+ patients recurrence-free after 5 years of endocrine therapy.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr S1-9.