Given recent data on genetic heterogeneity within and individual's tumor, we investigated if there were differences in the prognostic and predictive abilities of BCL2 and TP53 protein expression in primary breast cancer (TU) and corresponding axillary lymph-nodes (LN). We used patient samples from the adjuvant Belgian three-arm study which randomized between anthracycline containing regimens and traditional CMF. The endpoints analyzed were overall survival (OS), event-free survival (EFS) and interactions between chemotherapy regimens.At a median follow-up of 15.6 years, BCL2 and TP53 (in both TU and LN) were significantly associated with OS but only in the first 5 years. Likewise, BCL2 and TP53 (in both TU and LN) were associated with EFS in the first 2 years after randomization, with no association after 2 years. BCL2 and TP53 remained statistically significant after adjustment for the standard clinical-pathological characteristics in regard to OS and EFS in the respective first years after randomization, (p value < 0.001 for both markers).Furthermore, an interaction was found between high BCL2 expression in the TU (but not in LN) and benefit to CMF over anthracycline-based chemotherapy (interaction p value EFS: 0.042; OS = 0.01). No interaction was found for TP53 expression neither in TU nor in LN.We conclude that BCL2 and TP53 were predictive biomarkers for better and worse survival respectively, but only in the first two to five years after diagnosis. BCL2 expression in the TU but not in the LN was predictive of increased benefit to CMF vs anthracycline-based chemotherapy. © 2014 Elsevier Ltd. ; SCOPUS: ar.j ; info:eu-repo/semantics/published