Breast cancer response to paclitaxel in vivo

Abstract

Clinical trials using neoadjuvant (primary, preoperative) chemotherapy demonstrate that breast cancer reduction relates to survival. To date, no pre-treatment pathologic, phenotypic, or genotypic tumor characteristics predict a patient's likely benefit from paclitaxel. This has led to pilot clinical studies that have attempted to identify whether early cellular responses in vivo can be used to predict the effectiveness of chemotherapy. A potential benefit of such predictive studies will be the ability to tailor specific therapeutic approaches to individual patients. Important issues surrounding this field include how to accurately measure and/or categorize the extent of tumor reduction, and how and when to assess breast cancer cellular responses in vivo. Preliminary data indicate that initial apoptotic responses are critical to tumor reduction, and that the timing of tumor samples for assessment of response is important. Although inherent complete resistance of breast cancer to paclitaxel occurs in a minority of patients, mechanisms of acquired or partial resistance require further study. However, the initial apoptotic response to paclitaxel has been shown to transiently reduce both cell density and intratumoral pressure, providing a window of time when there can be improved penetration of paclitaxel into the tumor. Thus a strong initial apoptotic response can set up a compounding benefit from subsequent treatments. Knowledge of breast cancer response to paclitaxel in vivo could lead to therapeutic strategies that enhance the apoptotic response and optimize the dosing schedule, to improve the tumor reduction for most patients.