de Sá Alfonso López, Tejerina Julia, Amann Marta, Ballestín Pablo, González Beatriz, Pascual Alejandro, Del Arco Cristina Díaz, García-Barberán Vanesa, Paz-Cabezas Mateo, De Luna Alicia, García-Sáenz José Ángel, Moreno Fernando
Servicio de Oncología Médica, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria Hospital Clinico San Carlos (IdISSC), C/Professor Martin Lagos S/N, 28040, Madrid, Spain.
Clinical and Translational Research in Oncology Group, Molecular Oncology Laboratory, Hospital Clinico San Carlos, IdISSC, Madrid, Spain.
Clin Transl Oncol. 2025 Aug 20. doi: 10.1007/s12094-025-03999-7.
To evaluate the correlation between HER2 expression levels measured by HER2 mRNA using Oncotype DX and by immunohistochemistry (IHC) in hormone receptor-positive (HR+) and HER2-negative (HER2-) early breast cancer. In addition, we assessed whether low HER2 expression is associated with distinct clinicopathological characteristics and prognosis in our series.
We conducted a retrospective study that included 500 patients diagnosed with stage I-III HR+/HER2- breast cancer who underwent surgery and had Oncotype DX recurrence score determined between 2009 and 2023 at Hospital Clínico San Carlos, Madrid, Spain. HER2 mRNA levels obtained through Oncotype DX were compared across IHC groups (HER2 0+, HER2 1+, HER2 2+/ISH-negative). Event-free survival (EFS) was analyzed according to HER2 expression.
Although HER2 mRNA levels increased with higher IHC HER2 categories, variability and overlap were observed between subgroups. Median Oncotype DX recurrence scores also rose slightly across HER2 IHC groups but did not reach statistical significance. EFS did not differ between HER2 expression levels.
We found that HER2 mRNA measurement by Oncotype DX provides a quantitative approach to assess HER2 expression. However, its results overlap within traditional IHC categories. While HER2-low classification may have therapeutic implications for new antibody-drug conjugates, its prognostic relevance appears limited. Further studies are needed to improve HER2 quantification methods for improved clinical decision-making.
评估在激素受体阳性（HR+）和人表皮生长因子受体2阴性（HER2-）早期乳腺癌中，使用Oncotype DX检测的HER2 mRNA表达水平与免疫组织化学（IHC）检测结果之间的相关性。此外，我们还评估了低HER2表达是否与我们研究系列中的独特临床病理特征和预后相关。
我们进行了一项回顾性研究，纳入了500例诊断为I-III期HR+/HER2-乳腺癌的患者，这些患者在西班牙马德里的圣卡洛斯临床医院接受了手术，并在2009年至2023年期间测定了Oncotype DX复发评分。比较了通过Oncotype DX获得的HER2 mRNA水平在不同IHC组（HER2 0+、HER2 1+、HER2 2+/原位杂交阴性）中的情况。根据HER2表达分析无事件生存期（EFS）。
尽管HER2 mRNA水平随着IHC HER2分类的升高而增加，但各亚组之间存在变异性和重叠。HER2 IHC组的Oncotype DX复发评分中位数也略有上升，但未达到统计学意义。HER2表达水平之间的EFS没有差异。
我们发现，通过Oncotype DX检测HER2 mRNA提供了一种评估HER2表达的定量方法。然而，其结果在传统IHC类别中存在重叠。虽然HER-低分类可能对新型抗体药物偶联物具有治疗意义，但其预后相关性似乎有限。需要进一步研究以改进HER2定量方法，从而改善临床决策。
