Abstract C10: Class III β -tubulin predicts pathological response to neoadjuvant docetaxel-based chemotherapy in breast cancer patients.

Abstract

Abstract Background: Class III β-tubulin has been suggested as a potential predictor of taxane response for several cancers including breast cancer, although controversies exist. We evaluated correlations between class III β-tubulin and docetaxel response in neoadjuvant setting of breast cancer, focusing on pathological response which is considered the most powerful predictor of outcome. Materials and Methods: Fifty-five patients with primary breast cancer who had undergone neoadjuvant doxetaxel and adriamycin were included in this study. Class III β-tubulin was measured by immunohistochemistry in prechemotherapy paraffin-embedded tumor tissues. The cutoff value of ‘high’ and ‘low’ expression of class III β-tubulin was set at 50% of tumor cell staining. ‘Good pathological response’ was defined by pathological complete response (pCR) or microscopic residual disease (i.e., breast tumor ≤1cm and negative axillary node). The counterpart was designated as ‘poor pathological response’. Results: Before chemotherapy, 14 patients were in clinical stage II and 41 were in clinical stage III. After the median 4 cycles of preoperative chemotherapy, clinical downstaging was observed in 40 patients whereas clinical staging did not change in the remaining patients. Eleven patients (20%) showed good pathological response (pCR, 6; microscopic residual disease, 5) and 44 (80%) showed poor pathological response. Thirty-six (65.5%) and 19 patients (34.5%) were categorized into low and high class III β-tubulin groups, respectively. Low class III β-tubulin was associated with low histologic grade (P=0.052). However, in multivariate logistic regression adjusted by known prognostic factors including histologic grade, low expression of class III β-tubulin (hazard ratio = 11.1; P = 0.049) and triple negative status (hazard ratio = 6.86; P = 0.022) were independent predictors of good pathological response. At the median follow-up of 40.8 months after surgery, recurrence occurred in 11 patients (5 in low class III β-tubulin group; 6 in high). Low expression of class III β-tubulin showed a favorable risk of relapse (P=0.152) which did not reach statistical significance probably due to short follow-up period. Conclusions: Low expression of class III β-tubulin by immunohistochemistry predicts good pathological response to neoadjuvant docetaxel in breast cancer, suggesting implications for improving chance to define docetaxel-beneficial group in this setting. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C10.