Comparative Genomic Profiling of Second Breast Cancers following First Ipsilateral Hormone Receptor–Positive Breast Cancers

Purpose: We compared the mutational profile of second breast and variant allele frequency of the reported variants except for cancers (SBC) following first ipislateral hormone receptor–positive GATA3. Among the 30 most frequent gene alterations, ARIDIA, breast cancers of patient-matched tumors to distinguish new priNSD2, and SETD2 had statistically significant discordance rates in maries from true recurrences. paired samples. Seventeen paired samples (17.7%) exhibited com-Experimental Design: Targeted next-generation sequencing mon variants and were considered true recurrences; these patients using the Oncomine Tumor Mutation Load Assay. Variants were had a trend for less favorable survival outcomes. Among the 8 filtered according to their allele frequency ≥ 5%, read count ≥ 5X, patients with available tissue for CGH analysis and considered new and genomic effect and annotation. Whole genome comparative primaries by comparison of the mutation profiles, 4 patients had genomic hybridization array (CGH) was also performed to evaluate clonally related tumors. clonality. Conclusions: Patient-matched FBC and SBC analysis revealed Results: Among the 131 eligible patients, 96 paired first breast that only a minority of patients exhibited common gene variants cancer (FBC) and SBC were successfully sequenced and analyzed. between the first and second tumor. Further analysis using larger Unshared variants specific to the FBC and SBC were identified in cohorts, preferably using single-cell analyses to account for clon-71.9% and 61.5%, respectively. Paired samples exhibited similar ality, might better select patients with true recurrences and thereby frequency of gene variants, median number of variants per sample, better inform the decision-making process.