Abstract
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 impor?tance; 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. .
Highlights
The scenario of presurgical therapy of breast cancer within neoadjuvant setting has been proposed as an ideal in vivo model for studying the tumor biological features WKDW PLJKW EH UHOLDEOH PDUNHUV IRU WKH DVVHVVPHQW RI WXPRU UHVSRQVH WR WKHUDS\ DQGRU valuable indices for long-term disease outcome
The neoadjuvant clinical setting has been increasingly evaluated as an optimal study designed for the determination of breast cancer biological features, and the significance of their expression pattern as well as possible variations induced by therapy, to address the reliability of these ELRPDUNHUVDVSURJQRVWLFSUHGLFWLYHIDFWRUV,QDQDGYDQFHHOXFLGDWLQJVXUURJDWHPROHFXODU or cellular markers of tumor response to therapy, may provide, earlier biological insight into ERWKWKHPHFKDQLVPRIWXPRUJURZWKDQGGUXJVHQVLWLYLW\UHVLVWDQFH
Owing to the knowledge that many drugs are effective on actively proliferating cells [4] and more intriguingly, laboratory evidence which have shown that many anticancer agents with differing modes of action achieve cytotoxic effects, at least partly, by inducing apoptosis [5], has led to a reappraisal of traditional views of tumor response and resistance to cytotoxic drugs
Summary
The scenario of presurgical therapy of breast cancer within neoadjuvant setting has been proposed as an ideal in vivo model for studying the tumor biological features WKDW PLJKW EH UHOLDEOH PDUNHUV IRU WKH DVVHVVPHQW RI WXPRU UHVSRQVH WR WKHUDS\ DQGRU valuable indices for long-term disease outcome. The use of primary (neoadjuvant) chemotherapy offers the opportunity to test clinical relevance of the pattern of modifications in the cell phenotype induced by therapy with the tumor remaining in situ throughout treatment as an in vivo measure of response.
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