|Expression of ER-alpha 36, a Novel Variant of Estrogen Receptor alpha, and Resistance to Tamoxifen Treatment in Breast Cancer|
|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|
|WOS标题词||Science & Technology|
|关键词[WOS]||ENDOCRINE THERAPY ; GROWTH ; ASSOCIATION ; MECHANISMS ; STRATEGIES ; ONCOGENE ; CELLS ; HER-2 ; ASSAY|
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.
|项目编号||985-2-067-113 ; 30672419 ; DK070016 ; BCTR81906 ; LB-595|
|资助机构||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|
|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
|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.|
|APA||Shi, Liang.,Dong, Bin.,Li, Zhongwu.,Lu, Yunwei.,Tao Ouyang.,...&Xie, Yuntao.(2009).Expression of ER-alpha 36, a Novel Variant of Estrogen Receptor alpha, and Resistance to Tamoxifen Treatment in Breast Cancer.JOURNAL OF CLINICAL ONCOLOGY,27(21),3423-3429.|
|MLA||Shi, Liang,et al."Expression of ER-alpha 36, a Novel Variant of Estrogen Receptor alpha, and Resistance to Tamoxifen Treatment in Breast Cancer".JOURNAL OF CLINICAL ONCOLOGY 27.21(2009):3423-3429.|