αB-crystallin is a novel predictor of resistance to neoadjuvant chemotherapy in breast cancer
αB-crystallin is a novel predictor of resistance to neoadjuvant chemotherapy in breast cancer
复制标题
DOI：
10.1007/s10549-007-9796-0
复制
发表时间：
2008-10-01
影响因子：
3.8
通讯作者：
Cryns, Vincent L.
中科院分区：
文献类型：
--
作者：
Ivanov, Olga;Chen, Feng;Cryns, Vincent L.
目的α B-晶状体蛋白是一种抗凋亡蛋白，通常在预后不良的基底样乳腺肿瘤中表达，这些肿瘤主要是三重（雌激素受体（ER）、孕激素受体（PR）和HER 2）阴性。我们研究了乳腺癌中α B-晶状体蛋白表达是否与新辅助（术前）化疗的不良反应相关。方法112例接受新辅助化疗并有化疗后肿瘤标本可供分析的乳腺癌患者纳入本研究。49%的患者接受多柔比星和环磷酰胺（AC）治疗，37%的患者接受AC联合紫杉烷治疗，14%的患者接受其他治疗方案。33例患者的配对化疗前和化疗后肿瘤标本可用。通过组织微阵列中的免疫组织化学测定α B-晶状体蛋白表达。结果17%的肿瘤α B-晶体蛋白阳性。在33例有化疗前和化疗后肿瘤组织的病例中，有32例α B-晶体蛋白表达相同。α B晶体蛋白表达与ER阴性（P = 0.0024）和三阴性状态（P = 0.005）相关。总体缓解率（ORR）定义为治疗后肿瘤大小减少>= 50%，为53%（临床ORR）和61%（病理ORR）。尽管肿瘤分级、大小、ER、PR、HER 2或三阴性状态与缓解无关，但α B-晶状体蛋白阳性肿瘤的总体缓解率低于α B-晶状体蛋白阴性肿瘤（临床ORR分别为21%和59%，P = 0.0045;病理ORR分别为16%和70%，P < 0.0001）。结论α B-晶状体蛋白是一种新的生物标志物，主要在三阴性乳腺肿瘤中表达，可识别化疗耐药肿瘤的一个子集，这可能导致其预后不良。
Aims alpha B-crystallin is an anti-apoptotic protein commonly expressed in poor prognosis basal-like breast tumors, which are largely triple (estrogen receptor (ER), progesterone receptor (PR), and HER2) negative. We examined whether alpha B-crystallin expression in breast cancer was associated with a poor response to neoadjuvant (preoperative) chemotherapy. Methods One hundred and twelve breast cancer patients who received neoadjuvant chemotherapy and who had post-chemotherapy tumor specimens available for analysis were included in the study. Forty-nine percent of patients were treated with doxorubicin and cyclophosphamide (AC), 37% received AC in combination with a taxane, and 14% received other regimens. Paired pre- and post-chemotherapy tumor specimens were available for 33 patients. alpha B-crystallin expression was determined by immunohistochemistry in tissue microarrays. Results Seventeen percent of tumors were alpha B-crystallin positive. alpha B-crystallin expression was identical in 32 of 33 cases for which both pre- and post-chemotherapy tumor tissue was available. alpha B-crystallin expression was associated with ER-negative (P = 0.0024) and triple negative status (P = 0.005). Overall response rates (ORR) defined as >= 50% reduction in tumor size after treatment were 53% (clinical ORR) and 61% (pathological ORR). Although tumor grade, size, ER, PR, HER2 or triple negative status was not associated with response, alpha B-crystallin-positive tumors had poorer overall response rates than alpha B-crystallin-negative tumors (clinical ORR, 21% vs. 59%, respectively, P = 0.0045; pathological ORR, 16% vs. 70%, respectively, P < 0.0001). Conclusion alpha B-crystallin is a novel biomarker expressed predominantly in triple negative breast tumors that identifies a subset of chemotherapy-resistant tumors, which may contribute to their poor prognosis.