In vivo model for research of breast cancer biomarkers

The preoperative (neoadjuvant) setting of breast cancer treatment is an optimal in vivo model by which to allow the characterization of biomarker expression pattern with the tumor remaining in situ throughout treatment as an in vivo measure of response to particular therapy. Elucidating surrogate molecular or cellular markers of tumor response to therapy, may provide biological insight into both, the mechanism of tumor growth dynamics and drug sensitivity/resistance. Owing to the knowledge that many drugs are effective on actively proliferating cells and more intriguingly, that many anticancer agents with differing modes of action achieve cytotoxic effects by inducing apoptosis, has lead to a reappraisal of traditional views of tumor response/resistance to cytotoxic drugs in vivo. Accordingly, this review article will focus on discussing apoptosis phenomena and the p53 and bcl-2 protein as its regulators of principal importance; a cell proliferation determined by the Ki-67 expression, as the major counterbalancing process to apoptosis is also considered. This paper reviews the rationale for the use of these proteins as indices of tumor response to therapy, as well as the published literature regarding their clinical relevance. So far, no firm conclusions can be made concerning their predictive utility.