Abstract：
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.
摘要：
目的：随着新型抗HER2抗体-药物偶联物临床试验的有希望的数据的发布，HER2低表达乳腺癌(BC)有了新的治疗方向。本研究旨在评估HER2低阳性和HER2零BC临床病理特征的差异。包括对新辅助化疗（NACT）的反应和预后。
方法：回顾性收集2017年1月至2017年12月在我们的癌症中心接受NACT的HER2阴性（免疫组织化学[IHC]0、+1或+2未通过原位杂交[ISH]扩增）患者的记录。HER2-低阳性被定义为免疫组织化学(IHC)1+或IHC2+/原位杂交阴性,并且HER2-零被定义为IHC0。共同主要目标是比较两组之间的病理完全缓解（pCR）和无复发生存期（RFS）和总生存期（OS）。单变量和多变量逻辑回归模型和Cox比例风险模型用于分析终点pCR，RFS,和OS。
结果：总共283个肿瘤中有239个[84.5%]为HER2低阳性（包括132个[55.2%]HER2-1+和107个[44.8%]HER2-2+/ISH未扩增）和44个[15.5%]为HER2-0。HER2低阳性组患者的激素受体阳性率比HER2零患者高（188[78.7％]vs.19[43.2%]，P=0.000),但HER2-1+和HER2-2+/ISH非扩增之间没有差异(99[75.0%]vs.89[83.2%]，P=0.125）。HER2零肿瘤的pCR率明显高于HER2低阳性肿瘤（44例[34.1%]中的15例与239个中的22个[9.2%],P=0.000)。在激素受体阴性亚组中，HER2零肿瘤的病理完全反应也明显高于HER2低阳性肿瘤（25例中的13[52.0％]vs.51的14[27.5%]，P=0.036），但在激素受体阳性亚组中没有（19个中的2个[10.5％]对188个中的8个[4.3％]，P=0.231）。两组5年RFS比较差异无统计学意义(HR0.577,95%CI0.298~1.118,P=0.103)。然而,HER2低阳性肿瘤的OS明显优于HER2零肿瘤（HR0.280，95％CI0.122-0.697，P=0.006）。
结论：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，并对NACT和预后表现出不同的反应。
方法：回顾性收集2017年1月至2017年12月在我们的癌症中心接受NACT的HER2阴性（免疫组织化学[IHC]0、+1或+2未通过原位杂交[ISH]扩增）患者的记录。HER2-低阳性被定义为免疫组织化学(IHC)1+或IHC2+/原位杂交阴性,并且HER2-零被定义为IHC0。共同主要目标是比较两组之间的病理完全缓解（pCR）和无复发生存期（RFS）和总生存期（OS）。单变量和多变量逻辑回归模型和Cox比例风险模型用于分析终点pCR，RFS,和OS。
结果：总共283个肿瘤中有239个[84.5%]为HER2低阳性（包括132个[55.2%]HER2-1+和107个[44.8%]HER2-2+/ISH未扩增）和44个[15.5%]为HER2-0。HER2低阳性组患者的激素受体阳性率比HER2零患者高（188[78.7％]vs.19[43.2%]，P=0.000),但HER2-1+和HER2-2+/ISH非扩增之间没有差异(99[75.0%]vs.89[83.2%]，P=0.125）。HER2零肿瘤的pCR率明显高于HER2低阳性肿瘤（44例[34.1%]中的15例与239个中的22个[9.2%],P=0.000)。在激素受体阴性亚组中，HER2零肿瘤的病理完全反应也明显高于HER2低阳性肿瘤（25例中的13[52.0％]vs.51的14[27.5%]，P=0.036），但在激素受体阳性亚组中没有（19个中的2个[10.5％]对188个中的8个[4.3％]，P=0.231）。两组5年RFS比较差异无统计学意义(HR0.577,95%CI0.298~1.118,P=0.103)。然而,HER2低阳性肿瘤的OS明显优于HER2零肿瘤（HR0.280，95％CI0.122-0.697，P=0.006）。
结论：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，并对NACT和预后表现出不同的反应。
