Tau Expression and Efficacy of Paclitaxel Treatment in Metastatic Breast Cancer.

Purpose: Paclitaxel is widely used for the treatment of patients with metastatic breast cancer (MBC), such as in anthracycline-based combinations as a first-line chemotherapy. Although several mechanisms of paclitaxel resistance have been demonstrated, useful markers of paclitaxel resistance have not been available in clinical practice. A recent study revealed that low tau expression in cases of early breast cancer can predict susceptibility to paclitaxel administration in neoadjuvant therapy.Methods: In this study, the clinical significance of tau expression in MBC cases was established by identifying candidates with paclitaxel administration. Tissue specimens obtained from 35 patients who had received neither chemotherapy nor radiotherapy before surgery were examined. Status of tau expression was determined by immunohistochemistry.Results: Based on a previously reported classification scheme, 15 cases were classified as tau-negative (0, 1+) and 20 cases were classified as tau-positive (2+, 3+).Nine (60%) of 15 cases with tau-negative expression showed favorable response. Conversely, 17 (85%) of 20 cases with tau-positive expression showed progressive or stable disease after paclitaxel administration.Time to disease progression in tau-negative and tau-positive groups was 9.4 ± 6.6 months and 6.0 ± 3.7 months, respectively. Although no significant differences were apparent, this period tended to be longer in the tau-negative group.Discussion: Patients with tau-positive expression may derive less benefit than tau-negative from paclitaxel therapy in MBC. This suggests that tau expression could be used at diagnosis to select patients for whom paclitaxel treatment is likely to be of most benefit. However, this study has some clear limitations in terms of the modest sample size and the heterogeneity of eligible patients (e.g., different numbers and regimens for adjuvant and MBC chemotherapy). Many more cases must be examined before tau expression can be applied to practical clinical treatment. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1138.