Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom
Ivana Sestak , Yi Zhang , Dennis Sgroi , Catherine A. Schnabel , Jack M. Cuzick , Mitchell Dowsett
Background: The Breast Cancer Index (BCI) is a gene-expression based signature comprised of two complementary functional domains: the molecular grade index (MGI) for tumor proliferation, and the HoxB13/IL17BR ratio (H/I) for estrogen signalling. BCI provides a quantitative assessment of the likelihood of overall (0-10yr), late (5-10yr) DR and reported to show endocrine benefit in patients with estrogen receptor positive (ER+) breast cancer. The aim of the current study was to further characterize BCI performance to predict late DR for postmenopausal women with N- and N+ disease treated with either anastrozole or tamoxifen. Methods: 883 women with ER+, N- or N+ (1 to 3 nodes) breast cancer from TransATAC study who were recurrence free at 5 years were included in this analysis. Time to late DR (5 years after diagnosis) was the primary endpoint. Cox regression models were utilized to determine the prognostic value of the BCI and KM-estimates were used to determine 5-10 year DR. Results: 75 late DRs were recorded in all 883 patients who were recurrence free at 5 years. Patients with a high BCI score were associated with a significantly worse outcome compared to those with a low BCI score (HR = 1.88 (1.49-2.39)). This relationship was observed for both N- (HR = 1.96 (1.41-2.72)) and N+ (HR = 1.51 (1.08-2.12)) patients. BCI added significant prognostic information beyond that from CTS in all patients (∆LR-χ2= 11.51, P = 0.0007). For women with N- disease, significant differential risk stratification was observed between low and intermediate groups and between low and high groups. For N+ patients a significant difference was observed between low and high risk groups (HR = 3.10 (1.28-7.49)), but not low and intermediate or intermediate and high. For N+ patients, a BCI model integrating tumor size and grade provided significantly more prognostic value than BCI alone (LR-χ2= 21.34 vs. LR-χ2= 5.86, respectively). Conclusions: In this post-hoc analysis with an expanded group of patients from the TransATAC cohort, BCI was a significant prognostic factor for late DR in both N- and N+ patients, with a combined BCI model providing more prognostic value in N+ patients.
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