Department of Obstetrics and Gynecology, Otto-von-Guericke University, G.-Hauptmann Str. 35, 39108 Magdeburg, Germany.
Breast Cancer Res Treat. 2011 Jul;128(2):457-66. doi: 10.1007/s10549-011-1584-1. Epub 2011 May 24.
Recently, we have shown that the new G-protein-coupled estrogen receptor GPR30 plays an important role in the development of tamoxifen resistance in vitro. This study was undertaken to evaluate the correlation between GPR30 and tamoxifen resistance in breast cancer patients. GPR30 protein expression was evaluated by immunohistochemical analysis in 323 patients with primary operable breast cancer. The association between GPR30 expression and tamoxifen resistance was confirmed in a second cohort of 103 patients treated only with tamoxifen. Additionally, we evaluated GPR30 expression in 33 primary tumors and in recurrent tumors from the same patients. GPR30 expression was detected in 56.7% of the breast cancer specimens investigated and it correlated with overexpression of HER-2 (P = 0.021), EGFR (P = 0.024) and lymph node status (P = 0.047). In a first cohort, survival analysis showed that GPR30 was negatively correlated with relapse-free survival (RFS) only in patients treated with tamoxifen (tamoxifen with or without chemotherapy). GPR30 expression was associated with shorter RFS (HR = 1.768; 95% CI, 1.156-2.703; P = 0.009). In a subset of patients treated only with tamoxifen, multivariate analysis revealed that GPR30 expression is an independent unfavorable factor for RFS (HR = 4.440; 95% CI, 1.408-13.997; P = 0.011). In contrast, GPR30 tended to be a favorable factor regarding RFS in patients who did not receive tamoxifen. In 33 paired biopsies obtained before and after adjuvant therapy, GPR30 expression significantly increased only under tamoxifen treatment (P = 0.001). GPR30 expression in breast cancer independently predicts a poor RFS in patients treated with tamoxifen.
最近，我们已经证实，新的 G 蛋白偶联雌激素受体 GPR30 在体外的他莫昔芬耐药发展中发挥重要作用。本研究旨在评估 GPR30 与乳腺癌患者他莫昔芬耐药之间的相关性。我们采用免疫组化分析法对 323 例原发性可手术乳腺癌患者进行了 GPR30 蛋白表达评估。在仅接受他莫昔芬治疗的 103 例患者的第二队列中，确认了 GPR30 表达与他莫昔芬耐药之间的关联。此外，我们评估了 33 例原发性肿瘤和同一患者复发性肿瘤中的 GPR30 表达。在研究的乳腺癌标本中，GPR30 表达率为 56.7%，且与 HER-2（P=0.021）、EGFR（P=0.024）过表达和淋巴结状态（P=0.047）相关。在第一队列中，生存分析显示，仅在接受他莫昔芬治疗（他莫昔芬加或不加化疗）的患者中，GPR30 与无复发生存率（RFS）呈负相关。GPR30 表达与较短的 RFS 相关（HR=1.768；95%CI，1.156-2.703；P=0.009）。在仅接受他莫昔芬治疗的患者亚组中，多变量分析显示，GPR30 表达是 RFS 的独立不利因素（HR=4.440；95%CI，1.408-13.997；P=0.011）。相反，GPR30 似乎是未接受他莫昔芬治疗患者 RFS 的有利因素。在 33 例接受辅助治疗前后获得的配对活检中，仅在接受他莫昔芬治疗时 GPR30 表达显著增加（P=0.001）。在接受他莫昔芬治疗的患者中，GPR30 表达独立预测 RFS 不良。
