Department of OB/GYN, Medical University of Vienna, Vienna, Austria.
Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Clin Cancer Res. 2022 Sep 15;28(18):4112-4120. doi: 10.1158/1078-0432.CCR-21-4328.
Estrogen receptor (ER) expression is a prognostic parameter in breast cancer, and a prerequisite for the use of endocrine therapy. In ER+ early breast cancer, however, no receptor-associated biomarker exists that identifies patients with a particularly favorable outcome. We have investigated the value of ESR1 amplification in predicting the long-term clinical outcome in tamoxifen-treated postmenopausal women with endocrine-responsive breast cancer.
394 patients who had been randomized into the tamoxifen-only arm of the prospective randomized ABCSG-06 trial of adjuvant endocrine therapy with available formalin-fixed, paraffin-embedded tumor tissue were included in this analysis. IHC ERα expression was evaluated both locally and in a central lab using the Allred score, while ESR1 gene amplification was evaluated by FISH analysis using the ESR1/CEP6 ratio indicating focal copy number alterations.
Focal ESR1 copy-number elevations (amplifications) were detected in 187 of 394 (47%) tumor specimens, and were associated with a favorable outcome: After a median follow-up of 10 years, women with intratumoral focal ESR1 amplification had a significantly longer distant recurrence-free survival [adjusted HR, 0.48; 95% confidence interval (CI), 0.26-0.91; P = 0.02] and breast cancer-specific survival (adjusted HR 0.47; 95% CI, 0.27-0.80; P = 0.01) as compared with women without ESR1 amplification. IHC ERα protein expression, evaluated by Allred score, correlated significantly with focal ESR1 amplification (P < 0.0001; χ2 test), but was not prognostic by itself.
Focal ESR1 amplification is an independent and powerful predictor for long-term distant recurrence-free and breast cancer-specific survival in postmenopausal women with endocrine-responsive early-stage breast cancer who received tamoxifen for 5 years.
雌激素受体（ER）表达是乳腺癌的预后参数，也是内分泌治疗的前提。然而，在 ER+早期乳腺癌中，没有与受体相关的生物标志物能够识别具有特别良好预后的患者。我们研究了 ESR1 扩增在预测接受内分泌治疗的绝经后激素受体阳性早期乳腺癌患者长期临床结局方面的价值。
本分析纳入了 394 例接受前瞻性随机 ABCSG-06 试验内分泌辅助治疗的绝经后患者，这些患者随机分配至单独使用他莫昔芬组，并且有可用的福尔马林固定、石蜡包埋肿瘤组织。使用 Allred 评分评估局部和中心实验室的 IHC ERα 表达，而 ESR1 基因扩增则通过使用 ESR1/CEP6 比值指示局部拷贝数改变的 FISH 分析进行评估。
在 394 例肿瘤标本中，有 187 例（47%）检测到 ESR1 基因的局灶性拷贝数升高（扩增），并且与良好的结局相关：在中位随访 10 年后，肿瘤内存在局灶性 ESR1 扩增的女性远处无复发生存率显著延长[调整后的 HR，0.48；95%置信区间（CI），0.26-0.91；P = 0.02]和乳腺癌特异性生存率（调整后的 HR 0.47；95% CI，0.27-0.80；P = 0.01），与无 ESR1 扩增的女性相比。使用 Allred 评分评估的 IHC ERα 蛋白表达与局灶性 ESR1 扩增显著相关（P < 0.0001；卡方检验），但本身不具有预后价值。
在接受他莫昔芬治疗 5 年的接受内分泌治疗的绝经后激素受体阳性早期乳腺癌患者中，局灶性 ESR1 扩增是远处无复发生存率和乳腺癌特异性生存率的独立且强大的预测因素。
