北京大学临床肿瘤学院乳腺中心解云涛主任医师等新近的一项研究发现，在雌激素受体（ER-α）66阳性的乳腺癌患者中，ER-α36的过表达，是发生原发性他莫昔芬耐药的重要原因。相关研究结果发表在《临床肿瘤学杂志》（J Clin Oncol 2009，27（21）:3423）上。
解云涛介绍， ER-α66阳性是乳腺癌患者接受内分泌治疗的重要指标，尤其是对绝经前ER-α66阳性的乳腺癌患者。但临床上有约30%—40%的ER-α66阳性乳腺癌患者对他莫昔芬发生原发性耐药，不能从他莫昔芬治疗中获益。ER-α36受体是新发现的ER-α66变异体。
该研究将896例可手术的原发性乳腺癌患者分成2个队列分析：队列1纳入710例患者，其中ER-α66阳性者436例，这些患者无论是接受化疗联合他莫昔芬或单独接受他莫昔芬，ER-α36过表达均与无病生存率（DFS）和疾病特异生存率（DSS）低有关；队列2纳入186例患者，均接受他莫昔芬作为辅助治疗，在其中156例ER-α66阳性者中，ER-α36过表达与DFS和DSS低有关。
该研究表明，在ER-α66阳性的乳腺癌患者中，大约有40%的患者同时表达为ER-α36阳性。ER-α66和ER-α36均为阳性的患者不能从他莫昔芬治疗中获益。（生物谷Bioon.com）
生物谷推荐原始出处：
Journal of Clinical Oncology, Vol 27, No 21 (July 20), 2009: pp. 3423-3429
Expression of ER-α36, a Novel Variant of Estrogen Receptor α, and Resistance to Tamoxifen Treatment in Breast Cancer
Liang Shi, Bin Dong, Zhongwu Li, Yunwei Lu, Tao Ouyang, Jinfeng Li, Tianfeng Wang, Zhaoqing Fan, Tie Fan, Benyao Lin, Zhaoyi Wang, Yuntao Xie
From the Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Center, and Department of Pathology, Beijing Cancer Hospital and Institute, Peking University School of Oncology, Beijing, China; and Departments of Surgery and Pathology, Creighton University Medical School, Omaha, NE.
Purpose Recently, a 36-kDa variant of estrogen receptor (ER-α66), ER-α36, has been identified and cloned. ER-α36 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-36 expression and tamoxifen resistance in patients with breast cancer.
Patients and Methods ER-α36 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-α36 was associated with poorer disease-free survival (DFS) and disease-specific survival (DSS) in patients with ER-α66–positive tumors who received tamoxifen treatment (chemotherapy plus tamoxifen or tamoxifen alone, n = 307). In contrast, ER-α36 was not associated with survival in patients with ER-α66–positive tumors who did not receive tamoxifen (chemotherapy alone, n = 129) and in patients with ER-α66–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-α36 was significantly associated with poorer DFS and DSS in 156 ER-α66–positive patients from this cohort, and ER-α36 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-α66–positive tumors that also express high levels of ER-α36 are less likely to benefit from tamoxifen treatment.
