The Research Of Correlation Between The HER2 Expression And The Clinicopathological Characteristics And Prognosis Of Early Breast Cancer Patients Undergoing Trastuzumab-containing Therapy

Objective:Trastuzumab is the cornerstone drug for the targeted treatment of HER2(Human Epidermal Growth Factor Receptor 2,HER2)positive early breast cancer,but patients respond differently to trastuzumab.Currently the relationship between HER2 expression and prognosis of patients with HER2-positive breast cancer is not clear,and controversies exist in different studies.The study aims at investigating the relationship between different levels of HER2 expression and the clinicopathological characteristics and prognosis of patients who received Trastuzumab-containing therapy with breast cancer.Method:The information of 248 cases of early breast cancer diagnosed by puncture or biopsy was collected,and all of them were treated with anti-HER2targeted adjuvant therapy in the fourth hospital of Hebei Medical University from 2012 to 2015.Patients with HER2 positive were divided into two groups,the first group include patients diagnosed as HER2(3+)by Immunohistochemistry(IHC).It was divided into high and low expression group according to the proportion of cell membrane staining.The second group include patients with HER2(2+)and FISH amplification,it was divided into high and low expression group according to the ratio of HER2/CEP17.The relationship between HER2 positive expression in the two groups of patients and their clinicopathological characteristics and prognosis was analyzed.Results:1.In the first category of patients with HER2(3+),a total of 182 patients were enrolled,complete collection of case data and previous HER2 receptor slides,among which 8 slides that were not found were stained with new immunohistochemical staining,and 9 patients were lost to follow-up.The cut-off value of positive HER2 expression was calculated by the subject working characteristic curve method as 55%by the standard of cell membrane staining.It was defined that the proportion of membrane staining more than55%was high expression,and the proportion of membrane staining less than55%was low expression.Among them,155 patients(85.2%)in the high expression group and 27 patients(14.8%)in the low expression group.Chi-square test showed that the proportion of membrane staining was only related to the pathological grading(χ~2=6.55,P=0.038),and there was not statistical different between the proportion of membrane staining and the other pathological characteristics.Single-factor survival analysis showed that the presence or absence of lymph node metastasis was only related to the total survival of the patients(P=0.024),but was not related to DFS,while other pathological characteristics such as membrane staining ratio,age and tumor size were not associated with DFS and OS.Multivariate survival analysis showed that lymph node metastasis and histological grade were independent factors affecting OS in patients(P<0.05),while membrane staining ratio was not a factor influencing the prognosis of patients.2.In the second category of patients with HER2(2+)and FISH amplification,a total of 43 patients were enrolled and case date were completely collected,among which 14 patients without FISH information completed the new immunofluorescence staining and 2 patients were lost to follow-up.Taking HER2/CEP17 equal to 4 as the criterion,the patients were divided into high expression group and low expression group.Among them,8patients(18.6%)in the high expression group and 35 patients(81.4%)in the low expression group.Chi-square test showed that the ratio of HER2/CEP17was only associated with the Ki-67(χ~2=4.295,P=0.039),and was not related to other pathological features.Single-factor survival analysis showed that the ratio of HER2/CEP17 was associated with DFS(P=0.004),and lymph node metastasis was associated with DFS(P=0.046),and other pathological features were not associated with DFS.Multivariate survival analysis showed that the ratio of HER2/CEP17 was an independent factor for DFS(P=0.027).Conclusion:1.If 55%of membrane staining is used as the cutoff value of HER2positive expression,the proportion of membrane staining is only related to histological grading,but it is not a prognostic factor affecting patients.2.If 4 is taken as the cutoff value of HER2/CEP17 ratio,the ratio is related to Ki-67,and is an independent factor for DFS.The higher the ratio,the worse the prognosis.