CYP3A4 expression to predict treatment response to docetaxel for metastasis and recurrence of primary breast cancer

Abstract

Tumors expressing high levels of CYP3A4 are likely to have a poor treatment response to docetaxel (DOC), which is metabolized by CYP3A4. Tissue samples of recurrent breast cancer are sometimes hard to obtain just before treatment because the tumor is often difficult to access. Using immunohistochemistry, we measured CYP3A4 expression in primary lesions and compared their treatment responses to DOC with those of recurrent breast cancer lesions. The subjects of this study were 42 patients who had undergone surgery for breast cancer, and had metastasis or recurrence treated by DOC (60 mg/m(2) every 3 weeks). Tumor samples resected at surgery were immunostained for CYP3A4 and its expression levels were compared with the response rate to ongoing DOC treatment. Patients with CYP3A4-negative tumors (n = 19) showed a significantly higher response rate (63.2%) to DOC treatment than did those with CYP3A4-positive tumors (n = 23) (26.1%). The predictive value, negative predictive value, and diagnostic accuracy of CYP3A4 expression in the prediction response to DOC were 63.2%, 73.9%, and 68.6%, respectively. Measuring CYP3A4 expression immunohistochemically in the primary breast cancer lesion was useful for predicting the treatment response to DOC of tumors that recurred after a long interval.