Accurate Diagnosis Of Bilateral Breast Cancer Based On Clinicopathological Features And Whole Exome Sequencing

Background:Bilateral breast cancer(BBC)includes bilateral primary breast cancer and contralateral metastatic breast cancer,with poor prognosis and lower overall survival.Bilateral primary breast cancer could be considered an early-stage breast cancer,while contralateral metastatic breast cancer represents an advanced tumor.It is two different stages of tumor progression.Correctly distinguishing between bilateral primary breast cancer and contralateral metastatic breast cancer is of great significance to the accurate diagnosis,prognosis assessment and subsequent medication and treatment makingObjective:This study is to establish an accurate diagnosis method for the primary or metastatic breast cancer by combining clinical and pathological factors with Whole Exome Sequencing(WES)features.Further exploring the metastatic progression of contralateral metastatic breast cancer based on the differences in mutation sequences.Methods:Retrospectively analysis is made on the clinical characteristics of 30 BBC patients in our center from January 2010 to September 2019.According to the clinicopathological diagnostic criteria,the inditerminate bilateral breast cancer(IBBC),which is confused in diagnosis could be found out.Correlation analysis was performed on the clinicopathological characteristics of patients using Chi-square test or Fisher test,and the significance test level was ?=0.05.Samples of breast and axillary lymph nodes were investigated for single nucleotide variation,insertions and deletions,and somatic copy number variations,using WES.Then we distinguished them between a new primary and a true recurrence.Results:Thirty BBC patients had a median follow-up of 43 months.The age at initial diagnosis was 48.93±8.95 years.33.3%of patients were included in the IBBC group.Known driver genes were detected in the entire cohort,including TP53 and PIK3CA.In the ZHH group,72 non-synonymous mutations were detected in the left cancer and paired axillary lymph node,while the right side,with a higher Tumor Mutation Burden of 3.16 mutations/Mb,was found 500 non-synonymous mutations.There are no mutation overlap between the left and right side groups.The amplification in Chr 8q was found on the left side of ZHH,while the amplified signals were found on the right Chr17 and Chr7.The samples on the left and right side of the ZZH group shared 29 identical mutations and their allele variation frequencies were related(r=0.77).In addition,copy number variation of its left and right side was similar.Conclusion:Differential analysis of gene mutation profiles between bilateral breast cancer foci and matched metastatic lymph nodes can identify contralateral metastatic breast cancer and its inherent metastatic progression.The left breast tumor and the right one in ZHH developed independently,while the tumors on the left and right sides of ZZH originated from common ancestral cells,and the contralateral metastatic breast cancer develop in a linear progression model.WES,an evidence of molecular data,provides a viable method for the identification of new primary or metastatic breast cancer.In the future,we need to collect more research samples to verify the hypothesis of linear progress.