Department of Internal Medicine III With Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Paracelsus Medical University Salzburg, Müllner Hauptstraße 48, 5020, Salzburg, Austria.
Laboratory for Immunological and Molecular Cancer Research (LIMCR) and Center for Clinical Cancer and Immunology Trials (CCCIT), Salzburg Cancer Research Institute (SCRI), Salzburg, Austria.
Breast Cancer Res. 2021 Dec 14;23(1):112. doi: 10.1186/s13058-021-01492-x.
About 50% of all primary breast cancers show a low-level expression of HER2 (HER2-low), defined as immunohistochemically 1+ or 2+ and lack of HER2 gene amplification measured by in situ hybridization. This low HER2 expression is a promising new target for antibody-drug conjugates (ADCs) currently under investigation. Until now, little is known about the frequency and the prognostic value of low HER2-expression in metastatic breast cancer (MBC).
The MBC-Registry of the Austrian Study Group of Medical Tumor Therapy (AGMT) is a multicenter nationwide ongoing registry for MBC patients in Austria. Unadjusted, univariate survival probabilities of progression-free survival (PFS) and overall survival (OS) were calculated by the Kaplan-Meier method and compared by the log-rank test. Multivariable adjusted hazard ratios were estimated by Cox regression models. In this analysis, only patients with known HER2 status and available survival data were included.
As of 11/15/2020, 1,973 patients were included in the AGMT-MBC-Registry. Out of 1,729 evaluable patients, 351 (20.3%) were HER2-positive, 608 (35.2%) were HER2-low and 770 (44.5%) were completely HER2-negative (HER2-0). Low HER2-expression was markedly more frequent in the hormone-receptor(HR)+ subgroup compared to the triple-negative subgroup (40% vs. 23%). In multivariable analysis, low HER2 expression did not significantly influence OS neither in the HR+ (HR 0.89; 95% CI 0.74-1.05; P = 0.171) nor in the triple-negative subgroup (HR 0.92; 95% CI 0.68-1.25; P = 0.585), when compared to completely HER2-negative disease. Similar results were observed when HER2 IHC 2+ patients were compared to IHC 1+ or 0 patients.
Low-HER2 expression did not have any impact on prognosis of metastatic breast cancer in this real-world population.
约 50%的原发性乳腺癌表现出低水平的 HER2 表达（HER2-低），定义为免疫组织化学 1+或 2+，且原位杂交检测缺乏 HER2 基因扩增。这种低水平的 HER2 表达是目前正在研究的抗体药物偶联物（ADC）的一个有前途的新靶点。到目前为止，关于转移性乳腺癌（MBC）中低 HER2 表达的频率和预后价值知之甚少。
奥地利医学肿瘤治疗研究组（AGMT）的 MBC 登记处是奥地利 MBC 患者的一项多中心全国性登记处。无调整的单变量无进展生存期（PFS）和总生存期（OS）的生存概率通过 Kaplan-Meier 法计算，并通过对数秩检验进行比较。多变量调整的风险比通过 Cox 回归模型估计。在这项分析中，仅纳入了已知 HER2 状态和可获得生存数据的患者。
截至 2020 年 11 月 15 日，AGMT-MBC 登记处共纳入 1973 例患者。在 1729 例可评估的患者中，351 例（20.3%）为 HER2 阳性，608 例（35.2%）为 HER2-低，770 例（44.5%）完全为 HER2 阴性（HER2-0）。低 HER2 表达在激素受体（HR）+亚组中明显比三阴性亚组更为常见（40% vs. 23%）。多变量分析显示，低 HER2 表达在 HR+（HR 0.89；95%CI 0.74-1.05；P=0.171）和三阴性亚组（HR 0.92；95%CI 0.68-1.25；P=0.585）中均未显著影响 OS，与完全 HER2 阴性疾病相比。当比较 HER2 IHC 2+患者与 IHC 1+或 0 患者时，也观察到了类似的结果。
在这一真实世界人群中，低 HER2 表达对转移性乳腺癌的预后没有任何影响。
