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IR@PKUHSC  > 北京大学临床肿瘤学院  > 期刊论文
学科主题: 临床医学
题名:
Expression of ER-alpha 36, a Novel Variant of Estrogen Receptor alpha, and Resistance to Tamoxifen Treatment in Breast Cancer
作者: Shi, Liang; Dong, Bin; Li, Zhongwu; Lu, Yunwei; Tao Ouyang; Li, Jinfeng; Wang, Tianfeng; Fan, Zhaoqing; Fan, Tie; Lin, Benyao; Wang, Zhaoyi; Xie, Yuntao1
刊名: JOURNAL OF CLINICAL ONCOLOGY
发表日期: 2009-07-20
DOI: 10.1200/JCO.2008.17.2254
卷: 27, 期:21, 页:3423-3429
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: ENDOCRINE THERAPY ; GROWTH ; ASSOCIATION ; MECHANISMS ; STRATEGIES ; ONCOGENE ; CELLS ; HER-2 ; ASSAY
英文摘要:

Purpose Recently, a 36-kDa variant of estrogen receptor alpha (ER-alpha 66), ER-alpha 36, has been identified and cloned. ER-alpha 36 predominantly localizes on the plasma membrane and in the cytoplasm and mediates a membrane-initiated "nongenomic" signaling pathway. Here, we investigate the association between ER-alpha 36 expression and tamoxifen resistance in patients with breast cancer.

Patients and Methods ER-alpha 36 protein expression in tumors from 896 women (two independent cohorts, 1 and 2) with operable primary breast cancer was assessed using an immunohistochemistry assay.

Results In the first cohort of 710 consecutive patients, overexpression of ER-alpha 36 was associated with poorer disease-free survival (DFS) and disease-specific survival (DSS) in patients with ER-alpha 66 positive tumors who received tamoxifen treatment (chemotherapy plus tamoxifen or tamoxifen alone, n = 307). In contrast, ER-alpha 36 was not associated with survival in patients with ER-alpha 66 positive tumors who did not receive tamoxifen (chemotherapy alone, n = 129) and in patients with ER-alpha 66-negative tumors whether they received tamoxifen (n = 73) or not (n = 149). In the second cohort of 186 patients who only received tamoxifen as adjuvant therapy, overexpression of ER-alpha 36 was significantly associated with poorer DFS and DSS in 156 ER-alpha 66-positive patients from this cohort, and ER-alpha 36 remained an independent unfavorable factor for both DFS and DSS in these 156 patients by a multivariate analysis (DFS: hazard ratio [HR] = 5.47; 95% CI, 1.81 to 16.51; P = .003; DSS: HR = 13.97; 95% CI, 1.58 to 123.53; P = .018).

Conclusion Women with ER-alpha 66-positive tumors that also express high levels of ER-alpha 36 are less likely to benefit from tamoxifen treatment.

语种: 英语
所属项目编号: 985-2-067-113 ; 30672419 ; DK070016 ; BCTR81906 ; LB-595
项目资助者: Program for New Century Excellent Talents in University ; National Natural Science Foundation of China ; National Institutes of Health ; Susan G. Komen Breast Cancer Foundation ; Nebraska Tobacco Settlement Biomedical Research Program Award
WOS记录号: WOS:000268049100005
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/59782
Appears in Collections:北京大学临床肿瘤学院_期刊论文

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作者单位: 1.Creighton Univ, Sch Med, Dept Surg, Omaha, NE 68178 USA
2.Creighton Univ, Sch Med, Dept Pathol, Omaha, NE 68178 USA
3.Peking Univ, Sch Oncol, Breast Ctr,Minist Edu, Beijing Canc Hosp & Inst,Key Lab Carcinogenesis &, Beijing 100036, Peoples R China
4.Peking Univ, Sch Oncol, Beijing Canc Hosp & Inst, Dept Pathol, Beijing 100036, Peoples R China

Recommended Citation:
Shi, Liang,Dong, Bin,Li, Zhongwu,et al. Expression of ER-alpha 36, a Novel Variant of Estrogen Receptor alpha, and Resistance to Tamoxifen Treatment in Breast Cancer[J]. JOURNAL OF CLINICAL ONCOLOGY,2009,27(21):3423-3429.
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