Abstract P6-05-16: p53 and BCL2 expression across molecular subtypes: Correlation with disease progression, response to therapy and site of relapse in 1099 early breast cancer patients

Abstract

Abstract Background: The management of early breast cancer (BC) continues to be challenging because of the heterogeneity of the disease and a limited number of clinical/pathological factors are currently used to guide therapy and prognosis. Recently, p53, a tumor suppressor and BCL2, an antiapoptotic protein have been proposed as additional prognostic markers, although their relationship with conventional parameters and patient prognosis remains uncertain. In particular, there are few data concerning p53 and BCL2 distribution within the molecular BC subtypes, luminal A (LA), luminal B/HER2- (LB/HER2-), luminal B/HER2+ (LB/HER2+), HER2-like (H), and triple negative (TN). Methods: We conducted a retrospective study using immunohistochemistry to evaluate p53 and BCL2 expression in 1099 early BC patients (median age 56 yrs [21-92], N+ 487 [45%]) surgically treated at our Institute between 2000 and 2006 with at least 5 yrs follow-up data. None of the HER2+ patients, included in our series, received trastuzumab in the adjuvant setting. Associations among p53 and BCL2, T, N, G and molecular subtypes were analyzed by multiple correspondence analysis (MCA), while Kaplan-Meier method was applied to determine their impact on disease-free survival (DFS). Results: p53 and BCL2 differently distribute across the 5 molecular subtypes (p-value<0.0001). p53 is highly positive in LB-H+ (38%), H (50%) and TN (33%), conversely, BCL2 is more frequently expressed in LA (71%) and LB-H- (75%) BC. The relationships among bio-pathological factors, analyzed by MCA, confirmed that p53 positive and BCL2 negative BC are located in the quadrant containing more aggressive conventional tumor phenotypes (H and TN subtypes, T3/T4, N+, G3 and presence of relapse). Kaplan-Meier curves identified BCL2 negativity as a significant discriminating factor for DFS (p = 0.024) while p53 does not discriminate BC patients independent of molecular subtypes. Of interest, in the subset of 595 N0 patients p53 positivity and BCL2 negativity were significantly associated to the lack of response to anthracycline (AC ± taxanes) based chemotherapy (p<0.0001). Focusing on the 345 BC who relapsed (132 visceral and 213 non visceral metastases) we observed that visceral metastases are significantly less frequent in LA (30%), LB HER2- (37%) and TN (29%) BC as compared to H (52%) and LB-HER2+ (58%) BC (p = 0.004). Conclusions: Our data indicated that lack of BCL2, in contrast to p53 positivity, appears to be a biomarker related to a more aggressive clinical course across BC molecular subtypes although both biomarkers may affect AC-based chemotherapy response in the subset of N0 patients. Visceral metastases are more frequent in H and LB-HER+ subtypes as compared to the other groups. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-05-16.