Current neoadjuvant or adjuvant treatment strategies do not allow for rationale incorporation of such agents. One needs tools to predict both de novo and acquired resistance to therapeutic agents. This is a difficult task, due to the compound nature of escape routes: tumor exposure is usually to a combination of therapeutic agents and the mechanisms of resistance are broad: intrinsic resistance due to existing mutations, or regulatory - miRNA, other epigenetic - alterations, polymorphisms, tumor cell adaptation via new mutations and activation of alternative pathways, lack of optimal pharmacokinetics/genomics, activation of efflux mechanisms, accelerated repair mechanisms are involved.
Similarly, not all patients who are candidates for primary surgical intervention to be followed by post-operative adjuvant therapy benefit from such systemic treatments. The mechanisms of resistance be it de novo in surviving stem cell/tumorigenic components, or acquired by cells left behind "dormant" after the surgical intervention, are not well delineated.
Breast tumors subjected to neoadjuvant chemotherapy allow for baseline and treatment-effected sampling. Characterization of core biopsy specimens of primary tumors procured prior to exposure to neoadjuvant therapy from different varieties of breast cancer subtypes, and of subsequent mid-treatment and intraoperative (procured during definitive surgery following completion of neoadjuvant therapy) samples should help to assess the predictive value of the pre-treatment and post-treatment miRNA expression profile for complete and near complete response, as a surrogate marker for survival. Similarly, patterns of de novo and acquired resistance may emerge when assessment of pre- and post treatment miRNA expression profiles are analyzed in a supervised manner of classification using pathological response as classifier. Samples obtained from patients with primary surgical removal of their tumors before any systemic treatment exposure on the other hand, will allow for determining markers of prognosis, and predictors for response to therapeutic targeting agents.
Time Perspective: Retrospective/Prospective
