Clinical and molecular characteristics of estrogen receptor-positive ultralow risk breast cancer tumors identified by the 70-gene signature.
Clinical and molecular characteristics of estrogen receptor-positive ultralow risk breast cancer tumors identified by the 70-gene signature.
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DOI：
10.1002/ijc.33969
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发表时间：
2022-06-15
影响因子：
6.4
通讯作者：
Lindstrom, Linda S.
中科院分区：
文献类型：
--
作者：
Johansson, Annelie;Yu, Nancy Y.;Iftimi, Adina;Tobin, Nicholas P.;'t Veer, Laura;Nordenskjold, Bo;Benz, Christopher C.;Fornander, Tommy;Perez-Tenorio, Gizeh;Stal, Olle;Esserman, Laura J.;Yau, Christina;Lindstrom, Linda S.
雌激素受体（ER）阳性乳腺癌的转移潜力是异质性的，并且在初步诊断后数月至数十年发生远处复发。我们之前已经证明，通过70个基因签名被归类为超低风险的肿瘤患者患致命性乳腺癌的长期风险最小。在此，我们评估了来自斯德哥尔摩他莫昔芬随机试验（STO-3）的538例ER阳性患者中先前未探索的超低风险肿瘤的潜在临床和分子特征。在98个超低风险肿瘤中，89%为管腔A分子亚型，而26%的管腔A肿瘤为超低风险。与其他ER阳性肿瘤相比，超低风险肿瘤显著（Fisher检验，P < .05）更可能具有较小的肿瘤大小，较低的等级，孕酮受体（PR）阳性，人表皮生长因子2（HER 2）阴性，并且具有低Ki-67水平（增殖标记物）。此外，超低风险肿瘤显示与AKT/mTOR通路、增殖（AURKA）、HER 2/ERBB 2信号传导、IGF 1通路、PTEN缺失和免疫应答（IMMUNE 1和IMMUNE 2）相关的多基因模块的表达评分显著较低，而PIK 3CA突变相关模块的表达评分较高。此外，706个基因在超低风险肿瘤中显著（FDR < 0.001）差异表达，包括参与免疫应答、PI 3 K/Akt/mTOR通路、组蛋白、细胞周期、DNA修复、凋亡的基因表达较低，以及编码上皮-间充质转化和同源盒蛋白的基因表达较高等。总之，与致命性疾病的最小长期风险相关的超低风险肿瘤不同于其他ER阳性肿瘤，包括管腔A分子亚型肿瘤。识别这些特征对于提高我们对非致命性乳腺癌和致命性乳腺癌的预测是很重要的。 有什么新消息吗？ 雌激素受体（ER）阳性乳腺癌的转移潜力是异质性的，并且在初步诊断后可能发生数月至数十年的远处复发。然而，乳腺癌转移性疾病的长期风险在很大程度上仍未得到探索。使用先前建立的70个基因签名来识别具有最小长期致命疾病风险的乳腺癌患者，作者在这里表明超低风险肿瘤不同于其他ER阳性乳腺癌肿瘤，包括管腔分子亚型肿瘤。在临床乳腺癌标志物和分子特征方面存在差异。这些结果对于非致命性与致命性乳腺癌的表征和预测非常重要。
The metastatic potential of estrogen receptor (ER)‐positive breast cancers is heterogeneous and distant recurrences occur months to decades after primary diagnosis. We have previously shown that patients with tumors classified as ultralow risk by the 70‐gene signature have a minimal long‐term risk of fatal breast cancer. Here, we evaluate the previously unexplored underlying clinical and molecular characteristics of ultralow risk tumors in 538 ER‐positive patients from the Stockholm tamoxifen randomized trial (STO‐3). Out of the 98 ultralow risk tumors, 89% were luminal A molecular subtype, whereas 26% of luminal A tumors were of ultralow risk. Compared to other ER‐positive tumors, ultralow risk tumors were significantly (Fisher's test, P < .05) more likely to be of smaller tumor size, lower grade, progesterone receptor (PR)‐positive, human epidermal growth factor 2 (HER2)‐negative and have low Ki‐67 levels (proliferation‐marker). Moreover, ultralow risk tumors showed significantly lower expression scores of multi‐gene modules associated with the AKT/mTOR‐pathway, proliferation (AURKA), HER2/ERBB2‐signaling, IGF1‐pathway, PTEN‐loss and immune response (IMMUNE1 and IMMUNE2) and higher expression scores of the PIK3CA‐mutation‐associated module. Furthermore, 706 genes were significantly (FDR < 0.001) differentially expressed in ultralow risk tumors, including lower expression of genes involved in immune response, PI3K/Akt/mTOR‐pathway, histones, cell cycle, DNA repair, apoptosis and higher expression of genes coding for epithelial‐to‐mesenchymal transition and homeobox proteins, among others. In conclusion, ultralow risk tumors, associated with minimal long‐term risk of fatal disease, differ from other ER‐positive tumors, including luminal A molecular subtype tumors. Identification of these characteristics is important to improve our prediction of nonfatal vs fatal breast cancer. What's new? The metastatic potential of estrogen receptor (ER)‐positive breast cancers is heterogeneous, and distant recurrences may occur months to decades after primary diagnosis. However, the long‐term risk of metastatic disease in breast cancer remains largely unexplored. Using a previously‐established 70‐gene signature to identify breast cancer patients with minimal long‐term risk of fatal disease, here the authors show that ultralow‐risk tumors differ from other ER‐positive breast cancer tumors, including luminal molecular subtype tumors. Differences were found in both clinical breast cancer markers and molecular features. These results are important for the characterization and prediction of non‐fatal vs fatal breast cancer.
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影响因子：
14.9
作者：
The Gene Ontology Consortium
通讯作者：
The Gene Ontology Consortium
影响因子：
3.3
作者：
Engelberg, Jesse A.;Retallack, Hanna;Cardiff, Robert D.
通讯作者：
Cardiff, Robert D.
影响因子：
158.5
作者：
Cardoso, F.;van't Veer, L. J.;Piccart, M.
通讯作者：
Piccart, M.
影响因子：
168.9
作者：
Davies, C.;Godwin, J.;Gray, R.;Clarke, M.;Darby, S.;McGale, P.;Wang, Y. C.;Peto, R.;Pan, H. C.;Cutter, D.;Taylor, C.;Ingle, J.
通讯作者：
Ingle, J.
DOI：
10.1200/jco.2017.74.0472
发表时间：
2017-08-20
期刊：
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
影响因子：
--
作者：
Krop I;Ismaila N;Andre F;Bast RC;Barlow W;Collyar DE;Hammond ME;Kuderer NM;Liu MC;Mennel RG;Van Poznak C;Wolff AC;Stearns V
通讯作者：
Stearns V