Arenos Carl, Lim Steven, Lominoque Andreu, Reveldez Isabela, Sison-Dimaano Angeli, Pagandaman Nehar, Tatoy Vincent, Uy Timothy, Juan Michael San
https://orcid.org/0009-0001-6070-6924.
Division of Medical Oncology, Department of Medicine, University of the Philippines-Philippine General Hospital (UP-PGH), Manila 1008, Philippines.
Ecancermedicalscience. 2025 Feb 6;19:1840. doi: 10.3332/ecancer.2025.1840. eCollection 2025.
Human epidermal receptor 2 (HER2)-low breast cancer, characterised by specific immunohistochemistry (IHC) scores (+1 or +2) or negative fluorescence in-situ hybridiszation (FISH), has unique biological traits, therapeutic outcomes and prognosis. Recent studies highlight the effectiveness of Trastuzumab-Deruxtecan (T-Dxd) for HER2-low patients. This study seeks to deepen understanding of HER2 negative and low patients for tailored treatment by determining the 3-year disease-free survival (DFS) rates and prognostic variables of different subsets of HER2 negative (HER2 0) and HER2-low breast cancer patients (HER2 +1, HER2 +2 and HER2 FISH negative).
We analysed the records of 138 patients with non-metastatic breast cancer, exhibiting HER2 IHC 0, +1 or +2/FISH negative. Data on 3-year DFS in months, age, stage (early stage versus locally advanced) and menopausal status were collected. Kaplan-Meier survival curves were used to plot 3-year DFS, while Cox Proportional Analysis assessed the prognostic significance of age and menopausal status in the HER2-low population.
Three-year DFS for HER2 0 was 84.4%, HER2 +1 was 81.8% and HER2 +2/FISH negative was 52.9%, displaying statistically significant differences ( = 0.00012). Subgroup analyses revealed consistently worse DFS for HER2 +2/FISH negative patients in both early and advanced stages ( = 0.0042, 0.0057). Cox proportional analysis showed a recurrence hazard ratio of 4.0-4.5 for HER2 +2/FISH negative patients. Among prognostic factors, post-menopausal status correlated with a decreased risk of recurrence (HR 0.4387), signifying a 56.13% lower recurrence risk compared to pre-menopausal patients ( = 0.00723). On the other hand, patient age was not correlated with a reduced risk of recurrence (HR 0.97; = 0.0544).
This study reveals a worse 3-year DFS in HER2 +2/FISH negative patients across both early and advanced disease stages. The findings highlight the prognostic importance of HER2-low status and may guide future therapeutic strategies, including the use of targeted therapies like T-Dxd in non-metastatic patients.
人表皮生长因子受体2(HER2)低表达乳腺癌具有独特的生物学特性、治疗效果及预后,其特征为特定的免疫组化(IHC)评分(+1或+2)或荧光原位杂交(FISH)阴性。近期研究凸显了曲妥珠单抗-德曲妥珠单抗(T-Dxd)对HER2低表达患者的有效性。本研究旨在通过确定HER2阴性(HER2 0)和HER2低表达乳腺癌患者(HER2 +1、HER2 +2及HER2 FISH阴性)不同亚组的3年无病生存率(DFS)及预后变量,加深对HER2阴性及低表达患者的理解,以实现个体化治疗。
我们分析了138例非转移性乳腺癌患者的记录,这些患者表现为HER2 IHC 0、+1或+2/FISH阴性。收集了患者3年DFS(以月计)、年龄、分期(早期与局部晚期)及绝经状态的数据。采用Kaplan-Meier生存曲线绘制3年DFS,同时使用Cox比例分析评估年龄和绝经状态在HER2低表达人群中的预后意义。
HER2 0患者的3年DFS为84.4%;HER2 +1患者为81.8%;HER2 +2/FISH阴性患者为52.9%,差异具有统计学意义(P = 0.00012)。亚组分析显示,HER2 +2/FISH阴性患者在早期和晚期的DFS均持续较差(P = 0.0042,0.0057)。Cox比例分析显示,HER2 +2/FISH阴性患者的复发风险比为4.0 - 4.5。在预后因素中,绝经后状态与复发风险降低相关(HR 0.4387),这意味着与绝经前患者相比,复发风险降低了56.13%(P = 0.00723)。另一方面,患者年龄与复发风险降低无关(HR 0.97;P = 0.0544)。
本研究揭示了HER2 +2/FISH阴性患者在早期和晚期疾病阶段的3年DFS均较差。研究结果凸显了HER2低表达状态的预后重要性,并可能指导未来治疗策略,包括在非转移性患者中使用T-Dxd等靶向治疗。