It is still unclear whether bilateral breast cancer (BBC) should be regarded as relapsed, metastatic or second primary tumors. Using targeted next generation sequencing (NGS), we explored paired BBC genotypes to identify potential genomic similarities and clonal origin of these tumors.
We examined 76 patients (75 women and one man) with BBC, 52 concurrent and 24 metachronous. Paraffin tumors (n = 155) with informative targeted NGS data were histologically reviewed and subtyped with immunohistochemistry (IHC). In a patient subset, peripheral blood genotypes were obtained with the same panel and/or upon testing for cancer predisposing genes (germline testing). We analyzed coding mutations (amino acid changing, minor allele frequency
Breast histology and tumor IHC subtype were concordant in 85% and 61% of bilateral cases, respectively. We identified 258 mutations in 80 tumors (54 patients). TP53 and PIK3CA were the most frequently mutated genes (19% and 14%, respectively), followed by CDH1, GATA3 and MLL3. TP53 mutation rate was significantly higher in metachronous tumors (p
Clonal origin is revealed in few patients for the examined genes. The present findings support that BBC tumors are mostly independent tumors arising in the same patient, which justifies current clinical practice.
Clinical trial identification
Legal entity responsible for the study
Hellenic Cooperative Oncology Group
Hellenic Cooperative Oncology Group internal research grant
All authors have declared no conflicts of interest.