Danish Breast Cancer Cooperative Group Statistical Center; Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
International Breast Cancer Study Group Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, USA.
Ann Oncol. 2012 May;23(5):1138-1144. doi: 10.1093/annonc/mdr438. Epub 2011 Oct 10.
Estrogen Receptor 1 (ESR1) aberrations may be associated with expression of estrogen receptor (ER) or progesterone receptor (PgR), human epidermal growth factor receptor-2 (HER2) or Ki-67 labeling index and prognosis.
ESR1 was assessed in 1129 (81%) of 1396 postmenopausal Danish women with early breast cancer randomly assigned to receive 5 years of letrozole, tamoxifen or a sequence of these agents in the Breast International Group 1-98 trial and who had ER ≥ 1% after central review.
By FISH, 13.6% of patients had an ESR1-to-Centromere-6 (CEN-6) ratio ≥ 2 (amplified), and 4.2% had ESR1-to-CEN-6 ratio <0.8 (deleted). Deletion of ESR1 was associated with significantly lower levels of ER (P < 0.0001) and PgR (P = 0.02) and more frequent HER2 amplification. ESR1 deletion or amplification was associated with higher-Ki-67 than ESR1-normal tumors. Overall, there was no evidence of heterogeneity of disease-free survival (DFS) or in treatment effect according to ESR1 status. However, significant differences in DFS were observed for subsets based on a combination of ESR1 and HER2 status (P = 0.02).
ESR1 aberrations were associated with HER2 status, Ki-67 labeling index and ER and PgR levels. When combined with HER2, ESR1 may be prognostic but should not be used for endocrine treatment selection in postmenopausal women with endocrine-responsive early breast cancer.
雌激素受体 1（ESR1）异常可能与雌激素受体（ER）或孕激素受体（PgR）、人表皮生长因子受体-2（HER2）或 Ki-67 标记指数的表达以及预后有关。
在接受为期 5 年的来曲唑、他莫昔芬或这两种药物序贯治疗的 1396 例绝经后早期乳腺癌丹麦女性患者中，有 1129 例（81%）的患者的 ESR1 经中心评估后 ER≥1%，接受了评估。这些患者来自于乳腺癌国际研究组织 1-98 试验。
通过 FISH 检测，有 13.6%的患者 ESR1-着丝粒 6（CEN-6）比值≥2（扩增），4.2%的患者 ESR1-CEN-6 比值<0.8（缺失）。ESR1 缺失与 ER（P<0.0001）和 PgR（P=0.02）水平显著降低以及更频繁的 HER2 扩增相关。与 ESR1 正常肿瘤相比，ESR1 缺失或扩增的肿瘤 Ki-67 水平更高。总体而言，根据 ESR1 状态，无疾病生存（DFS）或治疗效果无明显异质性。然而，根据 ESR1 和 HER2 状态的组合，观察到亚组的 DFS 存在显著差异（P=0.02）。
ESR1 异常与 HER2 状态、Ki-67 标记指数以及 ER 和 PgR 水平有关。当与 HER2 联合使用时，ESR1 可能具有预后意义，但不应用于绝经后激素受体阳性早期乳腺癌患者的内分泌治疗选择。
