Use of molecular classification combined with p53 and topoisomerase IIa expression to identify tumors highly responsive to FEC regimen: A tissue microarray

Abstract

546 Background: Identification of highly responsive tumors to specific regimen is needed in order to better tailor post-operative chemotherapy regimen. We previously reported using a tissue microarrays that basal-like and HER2-overexpressing tumors derive higher benefit from adjuvant chemotherapy than luminal-like tumors. Previous studies have reported that p53+/basal-like tumors, and HER2+/topoisomerase IIa + tumors were highly sensitive to alkylating agents and anthracyclines respectively. In the present study, we have evaluated whether p53+/basal-like and HER2+TopIIa+ tumors derive high benefit from an alkylating/anthracyclines based chemotherapy. Methods: A tissue microarrays was built with tumor samples from 823 patients randomized between FEC/FAC regimen and no chemotherapy. Basal-like breast cancers were defined as HER2-/ER-/EGFR+ and/or CK5/6+ tumors. HER2-overexpressing were defined using HER2 expression by IHC (3+ score). P53 and topoisomerase IIa expression were assessed by IHC. Treatment effect was assessed by Cox model that included prognostic parameters and stratification variables. Predictive value for treatment effect were assessed by interaction test and test for heterogeneity. Results: 823 patients were included. 12.5% and 12.9% patients presented a basal-like and HER2-overexpressing breast cancer respectively. P53 and topoisomerase IIa were expressed in 20% and 35% patients. Hazard ratio for relapse associated with FEC/FAC regimen was 0.79 (95%CI: 0.62–1). Hazard ratio associated with FEC/FAC were 0.31 (0.1–0.97 ) and 1.19 (0.38–3.7 ) in patients with p53+/basal-like and p53- basal-like breast cancer. A p53/basal-based classification was associated with a trend for heterogeneity (p = 0.15). Hazard ratio associated with FEC/FAC were 0.34 (0.11–1.0 ) and 1.27(0.32–4.9) in patients with topIIa+/HER2+ and topIIa-/HER2+ breast cancer. A HER2/TopIIa classification was associated with a trend for heterogeneity (p = 0.07). Conclusions: The present study suggest that p53+/basal-like cancer and TopIIA+/HER2 cancers derive high benefit from adjuvant FEC/FAC regimen. This finding requires further validation given multihypothesis testing and subgroup analysis. No significant financial relationships to disclose.