HER-2低表达与零表达早期乳腺癌患者临床病理特征及预后分析

Analysis of the clinicopathologic and prognostic characteristics of early-stage breast cancer patients with HER-2 low expression and zero expression

背景与目的:临床上将HER-2低表达与HER-2零表达乳腺癌均被归类于HER-2阴性乳腺癌,并认为无HER-2靶向治疗条件。然而,近期的新型抗HER-2药物临床试验结果显示,HER-2低表达乳腺癌患者仍可从抗HER-2治疗中获益,使HER-2低表达与HER-2零表达乳腺癌患者之间生物学特性以及治疗反应与预后方面的差异备受关注。因此,本研究探讨HER-2低表达与HER-2零表达早期乳腺癌患者临床病理特征及预后差异,以期为临床提供更多的参考数据。方法:回顾性分析2010年1月—2020年12月间中南大学湘雅二医院乳腺外科收治并经病理确诊的1002例HER-2阴性早期乳腺癌(M0)患者临床资料,根据患者HER-2表达状态,将患者分为HER-2低表达组(409例)与HER-2零表达组(593例),比较两组患者相关临床病理指标与预后的差异。结果:与HER-2零表达组比较,HER-2低表达组浸润性导管癌比例更高(93.4%),且病理分化等级多表现为Ⅱ级(78.7%);HER-2低表达组TNM分期中处于T1的比例低于HER-2零表达组,而T2分期的比例高于HER-2零表达组,以上差异均有统计学意义(均P<0.05)。HER-2低表达组激素受体(HR)阳性率为87.5%,在199例检测了雄激素受体(AR)的患者中,AR阳性率80.9%,两项数据均高于HER-2零表达组(均P<0.05)。HER-2低表达组Ki-67表达量明显低于HER-2零表达组(P<0.05)。同时,两组间这些差异主要体现在HR阳性患者中(均P<0.05),而HR阴性患者中以上数据均未见明显差异(均P>0.05)。无论HR表达状况,HER-2低表达组与HER-2零表达组的总生存(OS)期和无病生存(DFS)期均无明显差异(均P>0.05)。此外,HER-2低表达患者中,AR表达状态对OS与DFS均无明显影响(均P>0.05)。结论:HER-2低表达与零表达早期乳腺癌患者间的临床病理特征存在一定差异,尽管两者的预后未见明显差异,但HER-2低表达患者的较高的HR与AR阳性率,以及较低的Ki-67表达水平,提示可能与内分泌治疗的敏感度相关。

Background and Aims:In clinical practice,both HER-2 low expression and HER-2 zero expression breast cancers are categorized as HER-2 negative breast cancer,and are considered ineligible for HER-2 targeted therapy.However,recent clinical trial results of new anti-HER-2 antibody have indicated that breast cancer patients with HER-2 low expression can still benefit from HER-2 targeted treatment.This has led to increased interest in the differences between breast cancer patients with HER-2 low expression and HER-2 zero expression in terms of the biological characteristics,treatment responses,and prognosis.Therefore,this study was performed to investigate the clinicopathologic characteristics and prognosis differences between early-stage breast cancer patients with HER-2 low expression and HER-2 zero expression,so as to provide additional data for clinical practice.Methods:The clinical data of 1002 HER-2 negative breast cancer patients with early-stage disease(M0)admitted to the Department of Breast Surgery,the Second Xiangya Hospital,Central South University,between January 2010 and December 2020 were retrospectively analyzed.Patients were categorized into the HER-2 low expression group(409 cases)and the HER-2 zero expression group(593 cases)based on their HER-2 expression status.The differences in relevant clinicopathologic variables and outcomes between the two groups were compared.Results:Compared to the HER-2 zero expression group,the HER-2 low expression group had a higher proportion of invasive ductal carcinoma(93.4%),with a majority exhibiting gradeⅡpathology(78.7%);the HER-2 low expression group had a lower proportion in the T1 stage and a higher proportion in the T2 stage according to TNM staging compared to the HER-2 zero expression group,and these differences were statistically significant(all P<0.05).In the HER-2 low expression group,the positivity rate of hormone receptors(HR)was 87.5%,and among the 199 cases tested for androgen receptor(AR),the AR positivity rate was 80.9%,both of which were higher than those in the HER-2 zero expression group(both P<0.05).Ki-67 expression was significantly lower in the HER-2 low expression group compared to the HER-2 zero expression group(P<0.05).These differences between the two groups were mainly observed in HR-positive patients(all P<0.05),while HR-negative patients showed no significant differences in all variables(all P>0.05).Regardless of HR expression status,there were no significant differences in overall survival(OS)and disease-free survival(DFS)between the HER-2 low expression group and the HER-2 zero expression group(all P>0.05).Additionally,in HER-2 low expression patients,the AR expression status had no significant impact on OS or DFS(all P>0.05).Conclusion:There are certain clinicopathologic differences between HER-2 low expression and zero expression early-stage breast cancer patients.Despite the lack of significant differences in prognosis between the two groups of patients,the higher HR and AR positivity rates,along with lower Ki-67 expression level in the HER-2 low expression group,suggest a potential association with sensitivity to endocrine therapy.