Abstract P4-11-19: Integration of breast cancer index (BCI) with clinicopathological factors for prediction of distant recurrence in ER+ breast cancer
Authors: Sestak Ivana , Zhang Yi , Schroeder Brock E , Goss Paul E , Dowsett Mitch , Sgroi Dennis C , Schnabel Catherine A , Cuzick Jack 
Published: May 2015

Abstract
Background: BCI is a genomic signature that significantly predicts risk of both early (0-5 years) and late (5-10 years) distant recurrence (DR) in hormonal receptor-positive, lymph node negative (LN-) breast cancer. In LN- disease, tumor size (TS) and grade (TG) are important independent prognostic factors of breast cancer recurrence. In this analysis, the effect of integrating these traditional clinicopathological factors on the ability of BCI to predict distant recurrence was evaluated in the translational arm of the Arimidex, Tamoxifen, Alone or in Combination trial (TransATAC).
Methods: 709 primary tumor samples from hormonal receptor-positive, LN- patients treated with 5 years of tamoxifen or anastrozole were examined. Multivariate Cox proportional hazards regression was used to fit 2 models: 1) BCI+TS; 2) BCI+TS+TG. To facilitate comparison across models, cut points were chosen based on the pre-specified 10 year DR rates of &lt;10% (low), 10-20% (intermediate) and &gt;20% (high). Kaplan-Meier (KM) estimates of 10 year DR and hazard ratios (HR) were examined. Change in likelihood ratio χ2 (LR-χ2) values were used to quantitate relative prognostic information beyond standard clinicopathological variables (CTS, Clinical Treatment Score).
Results: In the univariate analysis, all models were significantly prognostic for 10 year DR risk; BCI was somewhat less predictive vs BCI+TS, whereas TG did not provide significant additional value beyond BCI+TS [HR (95% CI): 3.26 (2.29-4.63), 2.72 (2.11-3.50), 2.72 (2.11-3.50); LR-χ2 (p value): 45.54 (p&lt;0.0001), 54.71 (p&lt;0.0001), 57.27 (p&lt;0.0001) for BCI, BCI+TS, BCI+TS+TG, respectively]. Adjusted HRs beyond CTS demonstrated highly significant and comparable prognostic ability [HR (95% CI): 2.35 (1.61-3.42), 2.06 (1.48-2.86); LR-χ2 (p value): 20.75 (p&lt;0.0001), 18.96 (p&lt;0.0001)] for BCI and BCI+TS, respectively. BCI and BCI+TS categorized similar proportions of patients into respective risk groups, and KM analysis comparing BCI vs BCI+TS risk categories showed similar rates of 10 year DR (Table 1).
Comparison of Risk Categorization and 10 year DRBCIBCI+TS% Patients10 year DR% Patients10 year DRLow Risk53.7%5.3%54.7%5.2%Intermediate Risk29.3%15.5%29.2%16.5%High Risk17.0%28.0%16.2%27.3%
In cross stratification analysis between BCI and BCI+TS, no significant re-classification was observed (Table 2), however 14.5% of BCI and 9.7% of BCI+TS intermediate risk patients were re-stratified as low risk.
Re-classification of BCI and BCI+TS for all patientsBCIBCI+TSLowIntermediateHighTotalLow358300388 (54.7%)Intermediate2016323206 (29.1%)High31498115 (16.2%)Total381 (53.7%)207 (29.2%)121 (17.1%)709
Discussion: Integration of tumor size, but not grade, statistically enhanced the prognostic ability of BCI to predict 10 year DR risk in patients with ER+, LN- early stage breast cancer. However, there was limited clinical impact on risk stratification, indicating that the prognostic information provided by these clinicopathological factors is effectively captured by BCI alone.
Citation Format: Ivana Sestak, Yi Zhang, Brock E Schroeder, Paul E Goss, Mitch Dowsett, Dennis C Sgroi, Catherine A Schnabel, Jack Cuzick. Integration of breast cancer index (BCI) with clinicopathological factors for prediction of distant recurrence in ER+ breast cancer [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 P4-11-19.