p53 Status Splits Triple-Negative Breast Cancers in Subgroups with Distinct Predictive and Prognostic Potential Value

• Published in: Cancer research (Chicago, Ill.) Ill.), 2009-12, Vol.69 (24_Supplement), p.2018-2018
• Main Authors: Alberti, S., Ambrogi, F., Pedriali, M., Piantelli, M., Querzoli, P., Nenci, I., Ellis, I., Boracchi, P., Coradini, D., Biganzoli, E.
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.SABCS-09-2018

Background: Triple-negative breast cancers largely encompass basal-like breast cancers, which demonstrate an aggressive clinical behaviour and poor prognosis. However, triple-negatives also include normal breast-like cancers, as identified by gene expression profiling, which have a better prognosis than basal-like cancers, but do not respond as well to neoadjuvant chemotherapy. Thus, a clear-cut distinction between the two subgroups is urgently needed. p53 is heterogeneously expressed in triple-negative cases, suggesting association to subgroups with diverse biological profiles. Hence, we comparatively analyzed p53 expression in triple-negative breast cancers from two independent case series.Material and Methods: Two independent breast tumor case series (633 cases from Ferrara University, Italy and 1076 cases from Nottingham University, UK) were analysed. Applying non-hierarchical algorithms, we have previously identified four breast tumor clusters, that possess markedly different prognosis: cluster [1], characterized by high values of ER/PR (good prognosis); cluster [2], with intermediate / heterogeneous ER/PR values (good prognosis); cluster [3], with low-to-nil ER (bad prognosis) and cluster [4] with low-to-nil PR and high HER2 values (bad prognosis) (Clin Cancer Res 2006;12:781-90). p53 expression in triple-negative cases belonging to the different clusters was analyzed.Results: p53 protein expression sharply subdivided the triple-negative Ferrara cases into two distinct subsets, that were tightly associated to clusters [2] or [3], respectively. Low-to-nil p53 levels were only observed in cluster [2] while overexpression of p53 was only seen in cluster [3].The triple-negative tumors of the Nottingham dataset were comparatively evaluated. Consistently with the data of the Ferrara case series, p53 similarly split this case series in p53-overexpressing and p53 low-to-nil triple-negative cases. p53 expression was associated with shorter relapse-free (Figure 2) and overall survival.Discussion: Our findings indicate that p53 expression can split triple negative breast cancers into sharply distinct subgroups, with critically different prognosis and prediction of drug response potential. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2018.