早期浸润性小叶乳腺癌患者中HER2低表达与临床病理特征的相关性：一项国际多中心研究
Association of HER2-low with clinicopathological features in patients with early invasive lobular breast cancer: an international multicentric study.
作者信息
Van Baelen Karen, Nguyen Ha-Linh, Richard François, Zels Gitte, Karsten Maria Margarete, Nader-Marta Guilherme, Vermeulen Peter, Dirix Luc, Dordevic Adam David, de Azambuja Evandro, Larsimont Denis, Maetens Marion, Biganzoli Elia, Wildiers Hans, Smeets Ann, Nevelsteen Ines, Neven Patrick, Floris Giuseppe, Desmedt Christine
机构信息
Department of Oncology, Laboratory for Translational Breast Cancer Research (LTBCR), KU Leuven, Box 810, Herestraat 49, O&N IV, Louvain, 3000, Belgium.
Department of Gynecological Oncology, University Hospitals Leuven, Louvain, Belgium.
出版信息
Breast Cancer Res. 2025 Jun 13;27(1):106. doi: 10.1186/s13058-025-02058-x.
PURPOSE
The antibody-drug conjugate trastuzumab deruxtecan has proven to be not only efficient in patients with HER2+ breast cancers (BC), but also in those patients with so-called HER2-low BC. HER2-low tumors are well described in the general BC population, but not in patients with invasive lobular carcinoma (ILC). Here, we aimed at analyzing the association of HER2-low with clinicopathological features and survival outcomes in patients with early-stage pure ILC.
METHODS
A multicentric retrospective cohort of patients diagnosed with stage I-III estrogen receptor positive (ER+) HER2 negative (HER2-) ILC between 01/01/2000 and 12/31/2020 was assembled. HER2- disease was categorized further by immunohistochemical (IHC) score into HER2 0, HER2 1+ and HER2 2+ following time appropriate ASCO/CAP guidelines from 2007 onward and by local guidelines prior to 2007. The association of HER2-low (HER2 1+ and 2+) with clinicopathological variables was assessed using multinomial logistic regression. Survival analyses were performed to evaluate the association of HER2-low with disease-free (DFS), distant recurrence-free (DRFS) and overall survival (OS).
RESULTS
The data of 2098 patients with ER+ HER2- ILC was collected of which 1103 (52.6%) had a HER2-low tumor. Of these 716 (34.1%) had an IHC score of HER2 1+ and 387 (18.4%) of HER2 2+. In multivariable analysis, both tumor size of ≥ 2cm (OR: 1.37; 95%CI 1.01 - 1.87; p-value 0.042) and multifocality (OR: 1.55; 95%CI 1.11 - 2.15; p-value 0.009) were associated with HER2-low. HER2-low was associated with worse DFS (HR: 1.32; 95%CI 1.06 - 1.66; p-value 0.015) and OS (HR: 1.42; 95%CI 1.12 - 1.81; p-value 0.004) as compared to HER2 0. No association of HER2-low with DRFS was observed.
CONCLUSIONS
HER2-low is present in more than half of the patients with early ER+ HER2- pure ILCs and is associated with larger tumor size and multifocality. HER2-low is associated with a worse DFS and OS as compared to HER2 0.
目的
抗体药物偶联物曲妥珠单抗德鲁替康已被证明不仅对HER2阳性乳腺癌（BC）患者有效，而且对所谓的HER2低表达BC患者也有效。HER2低表达肿瘤在一般BC人群中已有充分描述，但在浸润性小叶癌（ILC）患者中尚未见报道。在此，我们旨在分析HER2低表达与早期纯ILC患者临床病理特征及生存结局的相关性。
方法
收集了2000年1月1日至2020年12月31日期间诊断为I - III期雌激素受体阳性（ER +）、HER2阴性（HER2 -）ILC的患者的多中心回顾性队列。自2007年起，HER2阴性疾病根据免疫组织化学（IHC）评分按照当时适用的ASCO/CAP指南进一步分为HER2 0、HER2 1 +和HER2 2 +，2007年之前则按照当地指南分类。使用多项逻辑回归评估HER2低表达（HER2 1 +和2 +）与临床病理变量的相关性。进行生存分析以评估HER2低表达与无病生存期（DFS）、远处无复发生存期（DRFS）和总生存期（OS）的相关性。
结果
收集了2098例ER + HER2 - ILC患者的数据，其中1103例（52.6%）患有HER2低表达肿瘤。在这些患者中，716例（34.1%）的IHC评分为HER2 1 +，387例（18.4%）为HER2 2 +。在多变量分析中，肿瘤大小≥2cm（比值比：1.37；95%置信区间1.01 - 1.87；p值0.042）和多灶性（比值比：1.55；95%置信区间1.11 - 2.15；p值0.009）均与HER2低表达相关。与HER2 0相比，HER2低表达与较差的DFS（风险比：1.32；95%置信区间1.06 - 1.66；p值0.015）和OS（风险比：1.42；95%置信区间1.12 - 1.81；p值0.004）相关。未观察到HER2低表达与DRFS的相关性。
结论
超过一半的早期ER + HER2 - 纯ILC患者存在HER2低表达，且与较大的肿瘤大小和多灶性相关。与HER2 0相比，HER2低表达与较差的DFS和OS相关。
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