Department of Pathology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY, USA.
Clin Breast Cancer. 2013 Apr;13(2):103-8. doi: 10.1016/j.clbc.2012.11.003. Epub 2012 Dec 6.
Expression of class ΙΙΙ β-tubulin (βΙΙΙ-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 βΙΙΙ-tubulin expression in breast cancer correlated with pathologic characteristics and whether its expression was predictive of response to neoadjuvant chemotherapy.
We determined βΙΙΙ-tubulin expression in 85 breast cancers, including 41 localized breast cancers treated with primary surgery and 44 treated with neoadjuvant chemotherapy before surgery. βΙΙΙ-tubulin expression was evaluated by immunohistochemical methods and was correlated with pathologic characteristics and response to neoadjuvant chemotherapy using residual cancer burden (RCB) score.
High βΙΙΙ-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 βΙΙΙ-tubulin expression was associated with a significantly greater likelihood of achieving a good pathologic response to chemotherapy as reflected by lower RCB scores (P = .021).
This study reveals differential βΙΙΙ-tubulin expression in breast cancers of different histologic grades, hormone receptors, and HER2/neu status. It also suggests a potential role for βΙΙΙ-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 βΙΙΙ-tubulin status and further validation of this marker in a large study.
III 类 β-微管蛋白（βΙΙΙ-tubulin）的表达与几种人类恶性肿瘤（包括乳腺癌）的肿瘤进展和对紫杉烷类为基础的治疗的耐药性相关。然而，其在乳腺癌新辅助治疗环境中的预测价值仍未得到探索。本探索性研究的目的是确定乳腺癌中βΙΙΙ-tubulin 的表达是否与病理特征相关，以及其表达是否对新辅助化疗的反应具有预测性。
我们在 85 例乳腺癌中确定了βΙΙΙ-tubulin 的表达，包括 41 例接受原发性手术治疗的局限性乳腺癌和 44 例接受新辅助化疗后手术治疗的乳腺癌。通过免疫组织化学方法评估βΙΙΙ-tubulin 的表达，并使用残留肿瘤负荷（RCB）评分将其与病理特征和对新辅助化疗的反应相关联。
高βΙΙΙ-tubulin 表达与低分化高级别乳腺癌显著相关（P =.003），但与肿瘤大小、雌激素受体（ER）状态或人表皮生长因子受体 2（HER2）/neu 过表达无关。在接受新辅助化疗的 ER（-）肿瘤中，高βΙΙΙ-tubulin 表达与获得良好的化疗病理反应的可能性显著增加相关，表现为 RCB 评分较低（P =.021）。
本研究揭示了不同组织学分级、激素受体和 HER2/neu 状态的乳腺癌中βΙΙΙ-tubulin 的差异表达。它还表明，βΙΙΙ-tubulin 可能作为 ER（-）乳腺癌新辅助化疗反应的预测生物标志物发挥作用，这在以前的研究中尚未报道过。这些数据为考虑βΙΙΙ-tubulin 状态提供了强有力的依据，并为该标志物在大型研究中的进一步验证提供了依据。
