Li Jing-Jing, Yu Yue, Ge Jie
The First Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
Breast Cancer. 2023 May;30(3):364-378. doi: 10.1007/s12282-022-01431-4. Epub 2023 Jan 19.
With the release of promising data from clinical trials of novel anti-HER2 antibody-drug conjugates, there is a new therapeutic direction in HER2-low expression breast cancer (BC). This study aims to evaluate the differences in clinicopathological characteristics of HER2-low-positive and HER2-zero BC, including response to neoadjuvant chemotherapy (NACT) and prognosis.
Records of HER2-negative (immunohistochemistry [IHC] 0, + 1, or + 2 non-amplified by in situ hybridization [ISH]) patients who received NACT at our cancer center between January 2017 and December 2017 were retrospectively collected. HER2-low-positive was defined as immunohistochemistry (IHC) 1 + or IHC2 + /in-situ hybridization negative and HER2-zero was defined as IHC0. The coprimary objectives were to compare pathological complete response (pCR) and relapse-free survival (RFS) and overall survival (OS) between the two groups. Univariate and multivariable logistic regression models and Cox-proportional hazards models were performed for analysis of the endpoints pCR, RFS, and OS.
A total of 239 [84.5%] of 283 tumors were HER2-low-positive (including 132 [55.2%] HER2-1 + and 107 [44.8%] HER2-2 + /ISH non-amplified) and 44 [15.5%] were HER2-zero. Patients in the HER2-low-positive group had more commonly hormone receptor positivity than HER2-zero patients (188 [78.7%] vs. 19 [43.2%], P = 0.000), but there was no difference between HER2-1 + and HER2-2 + / ISH non-amplified (99 [75.0%] vs. 89 [83.2%], P = 0.125). HER2-zero tumors had a significantly higher pCR rate than HER2-low-positive tumors (15 [34.1%] of 44 vs. 22 [9.2%] of 239, P = 0.000). Pathological complete response was also significantly higher in HER2-zero tumors versus HER2-low-positive tumors in the hormone receptor-negative subgroup (13 [52.0%] of 25 vs. 14 [27.5%] of 51, P = 0.036), but not in the hormone receptor-positive subgroup (2 [10.5%] of 19 vs 8 [4.3%] of 188, P = 0.231). No significant difference was observed in 5-year RFS between the two groups (HR 0.577, 95% CI 0.298-1.118, P = 0.103). However, HER2-low-positive tumors showed significantly better OS than HER2-zero tumors (HR 0.280, 95% CI 0.122-0.697, P = 0.006).
These results suggest that HER2-low-positive tumors have specific biological characteristics according to the hormone receptor status and exhibit different responses to NACT and prognosis.
随着新型抗HER2抗体药物偶联物临床试验的有前景数据发布，HER2低表达乳腺癌（BC）出现了新的治疗方向。本研究旨在评估HER2低阳性和HER2零表达BC的临床病理特征差异，包括对新辅助化疗（NACT）的反应和预后。
回顾性收集2017年1月至2017年12月在我们癌症中心接受NACT的HER2阴性（免疫组化[IHC]0、+1或+2且原位杂交[ISH]未扩增）患者的记录。HER2低阳性定义为免疫组化（IHC）1+或IHC2+/原位杂交阴性，HER2零表达定义为IHC0。共同主要目标是比较两组之间的病理完全缓解（pCR）、无复发生存期（RFS）和总生存期（OS）。采用单变量和多变量逻辑回归模型以及Cox比例风险模型对终点pCR、RFS和OS进行分析。
283例肿瘤中共有239例[84.5%]为HER2低阳性（包括132例[55.2%]HER2-1+和107例[44.8%]HER2-2+/ISH未扩增），44例[15.5%]为HER2零表达。HER2低阳性组患者激素受体阳性的情况比HER2零表达患者更常见（188例[78.7%]对19例[43.2%]，P=0.000），但HER2-1+和HER2-2+/ISH未扩增之间无差异（99例[75.0%]对89例[83.2%]，P=0.125）。HER2零表达肿瘤的pCR率显著高于HER2低阳性肿瘤（44例中的15例[34.1%]对239例中的22例[9.2%]，P=0.000）。在激素受体阴性亚组中，HER2零表达肿瘤的病理完全缓解也显著高于HER2低阳性肿瘤（25例中的13例[52.0%]对51例中的14例[27.5%]，P=0.036），但在激素受体阳性亚组中无差异（19例中的2例[10.5%]对188例中的8例[4.3%]，P=0.231）。两组之间5年RFS未观察到显著差异（HR 0.577，95%CI 0.298-1.118，P=0.103）。然而，HER2低阳性肿瘤的OS显著优于HER2零表达肿瘤（HR 0.280，95%CI 0.122-0.697，P=0.006）。
这些结果表明，HER2低阳性肿瘤根据激素受体状态具有特定的生物学特征，并且对NACT和预后表现出不同的反应。
