基于基因瘢痕评分(GSS)探索乳腺癌中的同源重组修复缺陷(HRD)

Exploring homologous recombination deficiency(HRD) in breast cancer based on genomic scar score(GSS)

目的:使用基因瘢痕评分(GSS)描述中国乳腺癌人群的HRD状态,并对乳腺癌的HRD状态和临床特征进行统计学分析。方法:使用AmoyDx HRD Panel检测我院诊断的79例乳腺癌患者。根据拷贝数长度(LCN)、拷贝数部位(SCN)和拷贝数类型(TCN)确定基因组疤痕得分(GSS)。HRD阳性是指BRCA突变阳性和/或GSS得分≥50。HRD得分与临床特征之间的关系通过卡方检验和Fisher’s精确检验及Wilcoxon秩和检验进行统计分析。结果:在79例患者中,BRCA突变阳性率10.1%,HRD阳性率35.4%。在TNBC患者中,HRD阳性率为80%,BRCA突变阳性率26.7%。53.4%的TNBC患者BRCA突变阴性但HRD阳性。与HRD阴性的乳腺癌相比,HRD阳性乳腺癌明显更可能是Ki-67高(P<0.05)、ER阴性(P<0.05)和PR阴性(P<0.05)的肿瘤。HRD阳性率在TNBC(80%)中也明显高于Luminal A(7.7%,P<0.001)和Luminal B(27.7%,P<0.05)。结论:GSS是乳腺癌同源重组缺陷的重要检测工具,能帮助挖掘BRCA突变阴性但HRD阳性的乳腺癌人群。HRD状态与乳腺癌的ER、PR和Ki-67状态相关。

Objective:To reveal the land scape of HRD status in Chinese breast cancer population by using genomic scar score(GSS) and statistically analyze the HRD status and clinical characteristics of breast cancer.Methods:Using AmoyDx HRD Panel to detect 79 breast cancer patients diagnosed in our hospital.Genomic Scar Score(GSS) is determined according to the length of copy number(LCN),the site of copy number(SCN) and the type of copy number(TCN).HRD-positive was defined by BRCA positive and/or GSS score≥50.The relationship between HRD score and clinical characteristics were statistically analyzed by the Chi-square test, Fisher’s exact test and Wilcoxon rank sum test.Results:Of the 79 patients, approximately 10.1% were BRCA mutation positive.Approximately 35.4% of the patients were HRD positive.Among TNBC patients, the HRD positive rate was 80% and the BRCA mutation positivity rate was 26.7%.53.4% of TNBC patients were negative for BRCA mutation but positive for HRD.HRD-positive tumors were significantly associated with clinical Ki-67 high(P<0.05),ER negative(P<0.05),and PR negative(P<0.05).The incidence of HRD-positive was also significantly higher in TNBC(80%) than in the Luminal A(7.7%,P<0.05) and Luminal B(27.7%,P<0.05).Conclusion:GSS is an important tool for detecting homologous recombination deficiency in breast cancer and can help identify breast cancer populations with a negative BRCA mutation but positive for HRD.HRD is associated with ER,PR and Ki-67 status in breast cancer.