Department of Breast Surgery, The First Affiliated Hospital of Harbin Medical University, No. 23, Youzheng Street, Nangang District, Harbin, 150001, P.R. China.
Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China.
World J Surg Oncol. 2024 Sep 12;22(1):248. doi: 10.1186/s12957-024-03530-2.
The novel anti-HER2 antibody drug conjugates (ADCs) can effectively improve the long-term survival of patients with HER2-low expression breast cancer. However, pathological responses to neoadjuvant therapy (NAT) within HER2-low expression breast cancer, the relationship between pathological response and prognosis and the transformation of HER2 status are all now poorly understood.
The patients with HER2-0 and HER2-low expression breast cancer receiving NAT at Harbin Medical University Cancer Hospital between Jan. 2014 and Nov. 2018 were retrospectively explored. HER2 low expression refers to the IHC 1 + or 2 + and FISH negative. The Kappa test was utilized for analyzing the consistency rate of HER2 expression. To evaluate disease-free survival (DFS) and overall survival (OS), this research employed both the Kaplan-Meier analysis and the Cox regression.
In this study, 178 patients with HER2-0 and 344 patients with HER2-low expression breast cancer were included. In comparison with the HER2-0 group, it is shown that patients in the HER2-low group have more possibility to be younger compared to those 50 years old (P < 0.014), have more premenopausal patients (P < 0.001), a higher proportion of hormone receptor (HR) positive patients (P < 0.001), and less proportion of stage III V patients (P < 0.034). When NAT was finished, the pCR rate became 23.6% in the HER2-0 group while 22.1% in the HER2-low group, and there was also a higher pCR rate in HR- patients in comparison with that in HR + patients (P < 0.01). Considering HER2 expression inconsistency, the overall HER2 inconsistency rate was 30.4% (Kappa = 0.431, P < 0.01). Among patients initially diagnosed as HER2-0, 34% (N = 61) were re-diagnosed as HER2-low after NAT. After stratification by HR expression status, HR+/HER2-0 patients transformed to HER2-low after NAT in 37%, and 32% of HR- patients changed from HER2-0 to HER2-low. In this survival analysis, there were both better DFS rates (P = 0.009) and OS rates (P = 0.026) in the HR-/HER2-low patients in comparison with the HR-/HER2-0 patients, while the HER2-0 and HER2-low patients in the HR + group had no significant survival difference. Additionally, for non-pCR patients, there was better DFS (P = 0.029) and OS (P = 0.038) in the HER2-low group in comparison with that of the HER2-0 group, while no significant survival difference exists between pCR patients.
After HR stratification, there are unique clinical characteristics and prognostic outcomes in HER2-low expression breast cancer, which indicates the potential to become a specific molecular subtype of breast cancer. The significant instability of HER2-low expression status between primary tumor and residual invasive disease suggests that multiple detections of HER2 status should be emphasized in NAT strategies.
新型抗 HER2 抗体药物偶联物（ADC）可有效提高 HER2 低表达乳腺癌患者的长期生存率。然而，目前对 HER2 低表达乳腺癌新辅助治疗（NAT）的病理反应、病理反应与预后的关系以及 HER2 状态的转化仍知之甚少。
回顾性分析 2014 年 1 月至 2018 年 11 月在哈尔滨医科大学附属肿瘤医院接受 NAT 的 HER2-0 和 HER2 低表达乳腺癌患者。HER2 低表达是指免疫组化 1+或 2+且 FISH 阴性。采用 Kappa 检验分析 HER2 表达的一致性率。采用 Kaplan-Meier 分析和 Cox 回归评估无病生存（DFS）和总生存（OS）。
本研究纳入了 178 例 HER2-0 患者和 344 例 HER2 低表达乳腺癌患者。与 HER2-0 组相比，HER2 低表达组患者更年轻（P<0.014），绝经前患者更多（P<0.001），激素受体（HR）阳性患者比例更高（P<0.001），III 期和 IV 期患者比例更低（P<0.034）。NAT 结束时，HER2-0 组的 pCR 率为 23.6%，HER2 低表达组为 22.1%，HR-患者的 pCR 率高于 HR+患者（P<0.01）。考虑到 HER2 表达不一致，整体 HER2 不一致率为 30.4%（Kappa=0.431，P<0.01）。在最初诊断为 HER2-0 的患者中，有 34%（N=61）在 NAT 后被重新诊断为 HER2 低表达。按 HR 表达状态分层后，NAT 后 HR+/HER2-0 患者中有 37%转化为 HER2 低表达，HR-患者中有 32%从 HER2-0 转为 HER2 低表达。在生存分析中，与 HR-/HER2-0 患者相比，HR-/HER2 低表达患者的 DFS 率（P=0.009）和 OS 率（P=0.026）均更好，而 HR+组的 HER2-0 和 HER2 低表达患者的生存无显著差异。此外，对于非 pCR 患者，与 HER2-0 组相比，HER2 低表达组的 DFS（P=0.029）和 OS（P=0.038）更好，而 pCR 患者的生存无显著差异。
在 HR 分层后，HER2 低表达乳腺癌具有独特的临床特征和预后结局，这表明其可能成为乳腺癌的一个特定分子亚型。原发肿瘤和残留浸润性疾病之间 HER2 低表达状态的显著不稳定性表明，NAT 策略中应强调多次检测 HER2 状态。
