High Expression of Class III β-Tubulin Predicts Good Response to Neoadjuvant Taxane and Doxorubicin/Cyclophosphamide-Based Chemotherapy in Estrogen Receptor-Negative Breast Cancer

被引:26
作者
Wang, Yihong [1 ,2 ]
Sparano, Joseph A. [2 ,3 ]
Fineberg, Susan [1 ,2 ]
Stead, Lesley [2 ,3 ]
Sunkara, Jaya [1 ,2 ]
Horwitz, Susan Band [4 ]
McDaid, Hayley M. [2 ,3 ,4 ]
机构
[1] Montefiore Med Ctr, Dept Pathol, Bronx, NY 10467 USA
[2] Albert Einstein Coll Med, Bronx, NY 10467 USA
[3] Montefiore Med Ctr, Dept Med Oncol, Bronx, NY 10467 USA
[4] Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10467 USA
基金
美国国家卫生研究院;
关键词
Breast cancer; Chemotherapy; Class III beta-tubulin; Neoadjuvant; Predictive biomarker; PATHOLOGISTS GUIDELINE RECOMMENDATIONS; AMERICAN-SOCIETY; RESISTANCE; SENSITIVITY; PACLITAXEL; DOCETAXEL; OVEREXPRESSION; CARCINOMAS; MECHANISMS; MARKER;
D O I
10.1016/j.clbc.2012.11.003
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Class III beta-tubulin (beta III-tubulin) has been associated with tumor response to taxane-based therapies in breast cancer. However its role in the neoadjuvant setting has not been explored. We evaluated beta III-tubulin expression by immunohistochemistry in 44 patients, and found high expression associated with good pathologic response in estrogen receptor-negative (ER) breast cancers. Our results give strong reason to consider beta III-tubulin as a predictive biomarker for neoadjuvant chemotherapy response. Background: Expression of class III beta tubulin (beta III-tubulin) correlates with tumor progression and resistance to taxane-based therapies for several human malignancies including breast cancer. However its predictive value in a neoadjuvant setting in breast cancer remains unexplored. The objective of this explorative study was to determine whether beta III-tubulin expression in breast cancer correlated with pathologic characteristics and whether its expression was predictive of response to neoadjuvant chemotherapy. Patients and Methods: We determined beta III-tubulin expression in 85 breast cancers, including 41 localized breast cancers treated with primary surgery and 44 treated with neoadjuvant chemotherapy before surgery. beta III-tubulin expression was evaluated by immunohistochemical methods and was correlated with pathologic characteristics and response to neoadjuvant chemotherapy using residual cancer burden (ROB) score. Results: High beta III-tubulin expression was significantly associated with poorly differentiated high-grade breast cancers (P = .003) but not with tumor size, estrogen receptor (ER) status, or human epidermal growth factor receptor 2 (HER2)/neu overexpression. In ER- tumors treated with neoadjuvant chemotherapy, high beta III-tubulin expression was associated with a significantly greater likelihood of achieving a good pathologic response to chemotherapy as reflected by lower ROB scores (P = .021). Conclusion: This study reveals differential beta III-tubulin expression in breast cancers of different histologic grades, hormone receptors, and HER2/neu status. It also suggests a potential role for beta III-tubulin as a predictive biomarker for response in neoadjuvant chemotherapy for ER- breast cancer, which has not been previously reported. These data provide a strong rationale for considering beta III-tubulin status and further validation of this marker in a large study. Clinical Breast Cancer, Vol. 13, No. 2, 103-8 (C) 2013 Elsevier Inc. All rights reserved.
引用
收藏
页码:103 / 108
页数:6
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