北京大學(xué)臨床腫瘤學(xué)院乳腺中心解云濤主任醫(yī)師等新近的一項研究發(fā)現(xiàn),，在雌激素受體（ER-α）66陽性的乳腺癌患者中，ER-α36的過表達,，是發(fā)生原發(fā)性他莫昔芬耐藥的重要原因,。相關(guān)研究結(jié)果發(fā)表在《臨床腫瘤學(xué)雜志》（J Clin Oncol 2009，27（21）:3423）上,。
解云濤介紹,， ER-α66陽性是乳腺癌患者接受內(nèi)分泌治療的重要指標(biāo)，尤其是對絕經(jīng)前ER-α66陽性的乳腺癌患者,。但臨床上有約30%—40%的ER-α66陽性乳腺癌患者對他莫昔芬發(fā)生原發(fā)性耐藥,，不能從他莫昔芬治療中獲益。ER-α36受體是新發(fā)現(xiàn)的ER-α66變異體,。
該研究將896例可手術(shù)的原發(fā)性乳腺癌患者分成2個隊列分析：隊列1納入710例患者,，其中ER-α66陽性者436例，這些患者無論是接受化療聯(lián)合他莫昔芬或單獨接受他莫昔芬,，ER-α36過表達均與無病生存率（DFS）和疾病特異生存率（DSS）低有關(guān),；隊列2納入186例患者，均接受他莫昔芬作為輔助治療,，在其中156例ER-α66陽性者中,，ER-α36過表達與DFS和DSS低有關(guān)。
該研究表明,，在ER-α66陽性的乳腺癌患者中,，大約有40%的患者同時表達為ER-α36陽性。ER-α66和ER-α36均為陽性的患者不能從他莫昔芬治療中獲益,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
