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目的:探讨人表皮生长因子受体2（human epithelial growth factor receptor-2，HER-2）低表达乳腺癌患者的临床病理特征和预后影响因素。方法:回顾性分析2013年1月1日至2016年12月31日于蚌埠医学院第一附属医院行手术治疗HER-2非阳性823例乳腺癌患者的临床资料。收集其一般临床指标（年龄、发病部位、月经状况）、病理特征（肿瘤TNM分期、组织学分级、病理类型、腋窝淋巴结状态、Ki-67指数以及HER-2、孕激素受体的表达情况）、治疗方案（内分泌治疗、放疗和化疗方案）、生存状态（病理确诊时间、手术时间、复发或转移时间、死亡时间）。比较不同激素受体状态HER-2非阳性乳腺癌患者的临床病理特征，分析其10年无病生存期（disease free survival，DFS）和总生存期的影响因素。计数资料以例（ %）表示，组间比较采用χ 2检验；采用 Kaplan- Meier法绘制生存曲线，并通过 Log- rank检验分析各亚组无病生存率和总生存率的差异；采用单变量和多变量 Cox比例风险模型分析预后的影响因素。 P<0.05为差异有统计学意义。 结果:823例HER-2非阳性乳腺癌患者中，激素受体阳性657例（79.83%），阴性166例（20.17%）；HER-2零表达287例（34.87%），低表达536例（65.13%）。与激素受体阴性组比较，激素受体阳性组HER-2低表达比例更高［68.49%（450/657）比51.81%（86/166），χ 2=16.25， P<0.001］，Ki-67>30%的比例更低［32.57%（214/657）比72.29%（120/166），χ 2=86.69， P<0.001］。在激素受体阳性组中，与HER-2零表达亚组比较，HER-2低表达亚组患者发病年龄≥40岁和绝经的比例更低（χ 2值分别为4.94、4.01， P值分别为0.026、0.045），病理分期更晚（χ 2=4.14， P=0.042），腋窝淋巴结阳性率更低（χ 2=5.18， P=0.023）。多因素分析结果表明，原发肿瘤大小分期T3~T4期、Ki-67>30%和HER-2零表达为激素受体阳性HER-2非阳性乳腺癌患者10年DFS的危险因素（ HR值分别为2.840、2.010、2.652，95% CI：2.265~4.010，1.563~2471，1.983~3.441，均 P<0.001），原发肿瘤大小分期T3、T4期和Ki-67>30%为10年总生存期的危险因素（ HR值分别为1.923、1.954，95% CI：1.332~2.642，1.774~2.531， P值分别为0.041、0.012）；原发肿瘤大小分期T3、T4期和HER-2零表达为激素受体阴性HER-2非阳性乳腺癌患者10年DFS的危险因素（ HR值分别为2.096、1.885，95% CI：1.687~3.000，1.452~2.774， P值分别为0.026、0.005），区域淋巴结分期N1~N3期为10年总生存期的危险因素（ HR=1.982，95% CI：1.230~2.710， P=0.001）。 结论:HER-2低表达在激素受体阳性乳腺癌患者中比在激素受体阴性中更常见，HER-2零表达组和低表达组患者的部分临床病理特征之间存在异质性，HER-2低表达乳腺癌患者的预后优于HER-2零表达患者，且HER-2表达状态对预后有显著影响。

Objective:To investigate the clinicopathological features and prognostic factors of breast cancer patients with low expression of human epidermal growth factor receptor 2 (human epidermal growth factor receptor-2, HER-2).Methods:Retrospective analysis was made on the clinical data of 823 cases of breast cancer with HER-2 non positive treated by surgery in the First Affiliated Hospital of Bengbu Medical College from January 1, 2013 to December 31, 2016. Collect general clinical indicators (age, site of onset, menstrual status, etc.), pathological features (tumor TNM staging, histological grading, pathological type, axillary lymph node status, Ki-67 index, and expression of HER-2, ER, PR), treatment plans (endocrine therapy, radiotherapy, and chemotherapy plans), survival status (pathological diagnosis time, surgery time, recurrence or metastasis time, and death time). To compare the clinicopathological characteristics of HER-2 non positive breast cancer patients with different hormone receptor status, and analyze the influencing factors of DFS and overall survival. Non normally distributed econometric data are represented by M( Q1, Q3), and Wilcoxon rank sum test is used for comparison between the two groups; Count data is represented as an example (%), and χ 2 test is used for inter group comparison; Use Kaplan Meier method to plot survival curves, and analyze the differences in disease-free survival rate and overall survival rate among different subgroups through Log rank test; Use univariate and multivariate Cox proportional risk models to analyze the influencing factors of prognosis. P<0.05 indicates a statistically significant difference. Results:Among 823 HER-2 non positive breast cancer patients, 657 (79.83%) were hormone receptor positive and 166 (20.17%) were negative; 287 cases (34.87%) had zero expression of HER-2, and 536 cases (65.13%) had low expression. Compared with the hormone receptor negative group, the hormone receptor positive group had a higher proportion of HER-2 low expression (68.49% (450/657) compared to 51.81% (86/166), χ 2=16.25, P<0.001), and a lower proportion of Ki-67>30% (32.57% (214/657) compared to 72.29% (120/166), χ 2=86.69, P<0.001). In the hormone receptor positive group, compared with the HER-2 zero expression subgroup, the HER-2 low expression subgroup had a lower proportion of patients with onset age ≥ 40 years old ( P=0.026), a higher proportion of premenopausal women ( P=0.045), a later pathological stage ( P=0.042), and a lower positive rate of axillary lymph nodes ( P=0.023). Multivariate analysis showed that primary tumor size stage T3-T4, Ki-67 > 30% and HER-2 zero expression were risk factors for 10-year DFS and total survival of hormone receptor positive HER-2 non positive breast cancer patients (10-year DFS: HR values were 2.840, 2.010, 2.652, 95% CI: 2.265－4.010, 1.563－2.471, 1.983－3.441, all P=0.001; Overall survival: HR values were 1.923, 1.954, 95% CI: 1.332－2.642, 1.774－2.531, with P values of 0.041 and 0.012, respectively; Primary tumor size stage T3-T4 and HER-2 zero expression are risk factors for 10-year DFS in hormone receptor negative HER-2 non positive breast cancer patients ( HR values are 2.096 1.885, 95% CI: 1.687－3.000, 1.452－2.774, P values are 0.026 and 0.005, respectively). Regional lymph node stage N1-N3 is a risk factor for 10-year overall survival ( HR=1.982, 95% CI: 1.230－2.710, P=0.001). Conclusions:Low HER2 expression in HR Positive patients with breast cancer is more common than in TNBC.There is heterogeneity between the clinicopathological features of patients with zero expression of HER-2 and low expression of HER-2. The survival prognosis of patients with breast cancer with low expression of HER-2 is better than that of patients with zero expression of HER-2, and the expression of HER2 has a significant effect on survival and prognosis.