Automated quantification of apoptosis after neoadjuvant chemotherapy for breast cancer: early assessment predicts clinical response.

Abstract

A large body of evidence implicates apoptosis in the effects of cancer chemotherapeutic agents on tumor cells in vitro and tumor xenografts in vivo, but the predictive value of apoptosis as an early marker for clinical response in cancer patients remains unclear. We developed an automated, laser scanning cytometer-based method to quantify the percentage of tumor cells containing DNA fragmentation characteristic of apoptosis in tumor sections. We measured levels of apoptosis in a panel of 15 matched, 18-gauge core breast cancer biopsies obtained before and 48 h after neoadjuvant therapy with docetaxel plus doxorubicin or paclitaxel as part of two prospective clinical trials. The results revealed a strongly significant (P = 0.0023) association between chemotherapy-induced apoptosis and pathological response. If the results can be validated in a larger patient cohort, the method could be used to "tailor" therapy to optimize benefit in a patient-specific fashion.