Prognostic and predictive value of p53 and p21 in breast cancer.

The prognostic and predictive value of p53 has been extensively studied in breast cancer. p53 serves a multifunctional role as a transcriptional regulator, genomic stabilizer, inhibitor of cell cycle progression, facilitator of apoptosis, and also perhaps an inhibitor of angiogenesis. Abrogation of its function should therefore lead to a more aggressive breast cancer phenotype and a worse clinical outcome, and indeed the preponderance of studies confirm this, with the risk of recurrence and death increasing by 50% or more if p53 is abnormal. Lack of unanimity of results may be due to differences in technique, study design, or population, as well as the subjectivity inherent in some approaches; however, the complexity and random nature of genomic change present in cancer cells may well also contribute to the lack of unanimity. Because many anticancer agents may exert a therapeutic effect through genomic damage and subsequent triggering of apoptosis, and because p53 can respond to genomic damage and facilitate apoptosis, it can be hypothesized that an intact p53 would predict sensitivity to therapy. Present data in breast cancer, however, does not clearly indicate that this is the case. There are several potential explanations. Study designs to accurately test the predictive value of a molecular marker are more exacting and difficult to achieve than prognostic studies. There may also be multiple alternative pathways, not involving p53, that play a part in determining the therapeutic effect of a treatment. The prognostic value of a downstream effector of p53 has also been assessed, though less extensively. p21 is transcriptionally upregulated by p53 and is an inhibitor of cyclin-dependent kinases and thus of cell cycle progression. Higher levels of p21 might indicate a more indolent type of breast cancer. However, data from a number of clinical studies is very conflicting, and at present p21 is not a promising prognostic factor in breast cancer.