Expression of HER-2 and BRCA1/2 in triple-negative breast cancer tissues and their correlation with clinicopathological parameters and prognosis

SHEN Yang; LI Changfen; LI Hailong; WU Zhixiao; GUO Shanlan

doi:10.3969/j.issn.1007-8096.2025.07.004

Abstract：Objective To investigate the expression of human epidermal growth factor receptor 2(HER-2)and breast cancer susceptibility gene(BRCA)1/2 in triple-negative breast cancer(TNBC),and to analyze the relationship between HER-2 and BRCA1/2 with clinicopathological parameters as well as prognosis.Methods 150 TNBC patients who received treatment in our hospital from January 2018 to January 2019 were selected to detect HER-2 and BRCA1/2 by immunohistochemistry.Based on the expression of HER-2,the patients were divided into the negative group(HER-2 score was 0)and the low expression group(HER-2 score was 1+,or HER-2 score was 2+but FISH test showed no HER-2 gene amplification).According to the expression of BRCA1/2,they were divided into positive(BRCA1/2 score was 2+)and negative(BRCA1/2 score was 0)group.Next-generation sequencing technology was employed to determine BRCA1/2 gene mutations,and the patients were divided into BRCA1/2-positive group and BRCA1/2-negative group based on the mutation status of BRCA1/2 gene.The differences in clinicopathological parameters of TNBC patients with different HER-2 expression and BRCA1/2 expression were compared.Spearman correlation analysis was used to analyze the relationship between HER-2 expression,BRCA1/2 expression and clinical pathological parameters of TNBC patients.All patients were followed up for 5 years,and Kaplan-Meier was plotted to analyze the differences in progression-free survival(PFS)of TNBC patients with different HER-2 expression and BRCA1/2 expression.COX regression was used to analyze the factors affecting the prognosis of TNBC patients.Results 150 TNBC patients were enrolled in this study,with 105 cases having negative HER-2 expression and 45 cases having low HER-2 expression,with 56 cases showing positive BRCA1/2 expression and 94 cases showing negative BRCA1/2 expression.The percentage of histological grade III,positive lymph node metastasis,and TNM stage III-IV in the group with low HER-2 expression was higher than that in the group with negative HER-2 expression(P<0.05).Similarly,the percentage of histological grade III,positive lymph node metastasis,and TNM stage III-IV in the positive BRCA1/2 expression group was higher than that in the negative BRCA1/2 expression group(P<0.05).The expression of HER-2 and BRCA1/2 was positively correlated with histologic gradeing,lymph node metastasis and TNM staging in TNBC patients(P<0.05).The PFS of HER-2 negative TNBC patients was(48.71±1.40)months,while the PFS of HER-2 low expression TNBC patients was(30.12±1.01)months,and the PFS of HER-2 negative patients was longer than that of HER-2 low expression TNBC patients(Log Rank test,χ2=27.842,P<0.001).BRCA1/2 negative TNBC patients had a PFS of(42.73±0.42)months,and BRCA1/2 positive TNBC patients had a PFS of(34.56±0.60)months,which showed that the PFS was longer in BRCA1/2 negative patients than in BRCA1/2 positive patients(Log Rank test,χ2=66.408,P<0.001).Follow-up revealed that 51 TNBC patients died and 99 survived within 5 years,with a 5-year overall survival rate of 66.00%.COX analysis showed that positive lymph node metastasis,low HER-2 expression,and BRCA1/2 positivity were adverse factors affecting the prognosis of TNBC patients(P<0.05).COX analysis showed that positive lymph node metastasis,low HER-2 expression,and BRCA1/2 positivity were adverse factors affecting the mortality of TNBC patients within 5 years(P<0.05).Conclusion TNBC patients with low HER-2 expression and BRCA1/2 positivity have a worse prognosis,and are significantly associated with clinical pathological parameters such as tumor TNM staging,histological grading,lymph node metastasis and 5-year survival.