ER, HER2, and TOP2A expression in primary tumor, synchronous axillary nodes, and asynchronous metastases in breast cancer

ER, HER2, and TOP2A expression in primary tumor, synchronous axillary nodes, and asynchronous metastases in breast cancer
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DOI:
10.1007/s10549-011-1610-3
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发表时间:
2012-04-01
影响因子:
3.8
通讯作者:
Laenkholm, Anne-Vibeke
Laenkholm, Anne-Vibeke
中科院分区:
医学2区
文献类型:
--
作者:
Jensen, Jeanette Dupont;Knoop, Ann;Laenkholm, Anne-Vibeke

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在乳腺癌复发时,治疗目标是转移。然而,目前的做法是根据原发性肿瘤的生物标志物谱选择全身治疗。在本研究中,从疑似转移性病变中获得确证性活检,并与原发性肿瘤的ER、HER2和TOP2A进行比较。在前瞻性组织收集研究中,81名患者因疑似复发而进行了活检。纳入了额外的存档配对材料,总共有119例患者的配对原发性肿瘤,同步腋窝淋巴结(52例患者可用)和淋巴结转移可用于分析。通过免疫组化、显色原位杂交和荧光原位杂交对原发肿瘤、腋窝淋巴结和转移灶的ER、HER2和TOP2A表达进行重新分析和集中测定。在81例疑似复发的活检患者中,65例(80%)被诊断为复发性乳腺癌,3例(4%)被诊断为其他恶性肿瘤,6例(7%)为良性疾病,7例(9%)患者的活检不具有代表性。原发肿瘤和相应的非同步转移之间ER、HER2和TOP2A(异常与正常)状态的不一致性分别为12%(14/118)、9%(10/114)和23%(17/75)。与生物标志物不一致性和既往辅助治疗或活检部位无显著相关性。ER、HER2和TOP2A的表达显示不一致,其频率足以强调转移性病灶的确证性活检在复发性乳腺癌未来管理中的作用。
At recurrence of breast cancer, the therapeutic target is the metastases. However, it is current practice to base the choice of systemic treatment on the biomarker profile of the primary tumor. In the present study, confirmatory biopsies were obtained from suspected metastatic lesions and compared with the primary tumors with respect to ER, HER2, and TOP2A. In the prospective tissue-collection study, 81 patients had biopsy from a suspected relapse. Additional archived paired material was included, leaving a total of 119 patients with paired primary tumor, synchronous axillary nodes (available in 52 patients) and asyncronous metastases available for analysis. ER, HER2, and TOP2A expression of primary tumors, axillary nodes and metastases were re-analysed and determined centrally by immunohistochemistry, chromogenic in situ hybridization, and fluorescence in situ hybridization. Of the 81 patients with a biopsy from a suspected relapse, 65 (80%) were diagnosed with recurrent breast carcinoma, 3 (4%) were diagnosed with other malignancies, 6 (7%) had benign conditions, and in 7 (9%) patients the biopsy was non-representative. Discordance in ER, HER2, and TOP2A (aberration vs. normal) status between primary tumor and corresponding asynchronous metastasis was 12% (14/118), 9% (10/114), and 23% (17/75), respectively. There were no significant associations with biomarker discordance and prior adjuvant therapy, or location of biopsy. Expression of ER, HER2, and TOP2A displayed discordance with a sufficient frequency to emphasize the role of confirmatory biopsies from metastatic lesions in future management of recurrent breast cancer.