The Clinicopathologic Characteristic And BRCA1/2 Mutation In Familial Breast Cancer

Objective1?To compare the differences of clinical and pathology features between familial breast cancer and sporadic breast cancer.2?To explore the patents and characteristic of BRCA1/2 mutations among Chinese familial breast cancer.3?To explore the relationship between BRCA1/2 mutation and incident of breast cancer within a family through pedigree study.Method1?Using 1:2 paring control study,We analyzed Clinical and pathological data of 35 breast cancer patients with family history?One or more first or second or third-degree relatives with breast cancer?and 70 sporadic breast cancer patients,who were diagnosed and treated in department of breast surgery in Guangdong Women and children's Hospital between May 2012 to November 2016.2?24 familial breast cancer patients have accepted BRCA detection.Amplifying and detecting the entire coding exons sequences of BRCA1/2 by NGS.3?To investigate the relationship between BRCA1/2 pathogenic mutation and incident of breast cancer in family members,a pedigree study was carried out.Results1?Clinicopathologic characteristic betweens familial breast cancer and sporadic breast cancer:1)There were no significant differences between familial and sporadic groups according to tumor size?pathological type?histological grade?axillary lymph node metastasis rate ?ER?PR?Her-2?ki-67.2)Compared with sporadic breast cancer patients,much more familial breast cancer patients were diagnosed with benign breast disease before,the percentage of familial and sporadic cancer patients with benign breast disease was 20% and 1.4%,respectively,difference between the two groups was statistically significant?P=0.01?.The premenopausal state were found in 85.7% of familial cases vs 68.9% of sporadic cases?P=0.02?.Bilateral breast cancer were observed in 35% of familial cases,while not even one of sporadic cases.Moreover,familial breast cancer patients present especially triple-negative breast cancer?P=0.04?.2?Detection of BRCA gene in familial breast cancer1)24 familial breast cancer patients accepted BRCA gene detection,5 mutation were identified in 7 familial breast cancer patients,the frequency of BRCA mutation were 22.9%,mutation rate of BRCA1 and BRCA2 was 12.5% and 8.3%,respectively.2)Among 5 mutation?BRCA1 C4258T?BRCA1 2110₂111delAA?BRCA1 5335delC?BRCA2 G8632C?BRCA2 C3109T?,4 of them were reported previously,the other one?BRCA2 G8632C?was first reported in this article.BRCA2 G8632 C was confirmed as a pathogenic mutation through Sanger sequencing.3?Result of pedigree study in BRCA2 G8632 C carrierThe investigation of the first-degree relatives of BRCA2 G8632 C carrier found that the father of proband in the case carried the mutation while the mother was not,neither of them suffered from breast cancer.There are 6 siblings of the proband,one of them is male,healthy and not carrying the mutation;five others are female,four of them?80%?carry the mutation.Of whom carry the mutation,three were diagnosed of breast cancer while the other one was not and 30 years old by now.The proband has a daughter carrying the mutation,healthy and 9 years old by now.Conclusion1 ? Comparing to sporadic breast cancer patients,a higher percentage of premenopausal women?bilateral breast cancer?triple-negative breast cancer were found in familial breast cancer patients.2?The frequency of BRCA mutation in familial breast cancer patients is 22.9%,all of the mutations are not hot spot of mutations reported previously.Therefore,detecting the entire coding exons sequences of BRCA1/2 by NGS is more suitable for Chinese BRCA screening.3?Through pedigree study,mutation site BRCA2 G8632 C,which was first reported by this article,is confirmed as a pathogenic mutation.