Clinical studies of Bcl-2 and treatment benefit in breast cancer patients

Interest in translational studies aimed at investigating the role of biolog ic markers in predicting clinical outcome of breast cancer patients and, in particular, response to specific treatments, has progressively increased. Among biologic variables presently under investigation, apoptosis markers, in particular Bcl-2 and Bax expression, are receiving much attention for th eir relationship with the cellular response to genotoxic damage in experime ntal tumors. Retrospective, independent studies were carried out by several research groups on about 5000 patients with, breast cancer at different st ages and with an adequate follow-up. The outcome of separate analyses,as a function of treatment generally demonstrated that Bcl-2 overexpression, whi ch correlates with biologic features of a differentiated phenotype (slow pr oliferation, high steroid receptor levels, absence of p53 and c-erB-2 expre ssion), is associated with a favorable outcome. Such a finding is mainly ev ident following surgery as well as endocrine treatment. Conversely, no or w eak Bcl-2 expression, alone or in association with bax overexpression, appe ars indicative of a radiation response, and preliminary emerging evidence s upports the involvement of such an association of apoptosis-related markers even as predictors of long-term response to neoadjuvant cytotoxic treatmen t. Although the findings of an involvement of Bcl-2 and Bax as determinants of treatment response should be confirmed within the context of randomized clinical trials, they indicate a combined consideration of proteins that n egatively and positively regulate apoptosis in translational studies on the effect of chemical and physical agents at a cellular level.