Whole‑exome sequencing insights into synchronous bilateral breast cancer with discordant molecular subtypes

The incidence of synchronous bilateral breast cancer (SBBC) is very low, and SBBC with discordant molecular subtypes is even more uncommon. As such, little is known about the pathogenesis of SBBC with discordant molecular subtypes, and reports about this entity are scarce. In the present study, the case of a 72-year-old female patient who presented with SBBC with discordant molecular subtypes is reported, with a stage IA hormone receptor negative {human epidermal growth factor receptor-2 [HER2(+)]} tumor in the left breast and a stage IIIA hormone sensitive tumor [HER2(-)] in the right breast. Whole-exome sequencing was performed to identify the differential genetic variations in the BBC tissues. A total of 8 key mutated cancer susceptibility genes (ALK, BRCA1, FAT1, HNF1A, KDR, PTCH1, SDHA and SETBP1) were screened, and mutations were found in 10 vital cancer driver genes, including BRCA1, EBF1, MET, NF2, NUMA1 RALGAPA1, ROBO2, SMYD4, UBR5 and ZNF844. The high-frequency mutated genes mainly contained missense mutations, among which single nucleotide variants were the most common mutations, with C > T and C > A as the main forms. The pathways associated with the high frequency mutated genes were further elucidated by functional category and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Heterogeneity in the hormone receptor and HER2 status of SBBC poses unique therapeutic challenges. Future studies should aim to identify the optimal management strategy for this disease.