Clin Cancer Res: New Genomic Features of Metastasis Breast Cancer!

Unlike stage I-III breast cancer (relapsed metastasis breast cancer (rMBC) that relapses after initial diagnosis, new metastasis breast cancer (dnMBC) represents a unique context in which the metastasis drivers are clarified in the absence of treatment options.
study explores the genome spectrum of dnMBC and its correlation with overall survival (OS).
researchers looked at primary or metastasis tumors (OncoPanel) in 926 patients (212 dnMBC and 714 rMBCs).
compared single nucleotide variation, copy number variation, and tumor mutation load (TMB) of primary dnMBC primary tumors with primary tumors in patients who eventually developed rMBC and associated them with all dnMBC OS.
the mutation characteristics of patients with rMBC and dnMBC were more intensive than the MYB amplification of rMBC (21.1% vs 0%, p=0.0005, q=0.111) when comparing primary tumors by subtype.
Compared with rMBC, KMTD2, SETD2, and PIC3CA mutations were more common in dnMBC primary HR-/HER2-tumors, and TP53 and BRCA1 mutations were less common, with the above differences not significant with multiple comparison adjustments.
the prognostication of patients with different mutation characteristics associated with OS shortening in dnMBC patients included TP53 (wild vs mutants: 79.7 vs 44.2 months; p=0.008, q=0.107), MYC (79.7). 7 vs 23.3 months; p=0.0003, q=0.011), and cell cycle (122.7 vs 54.9 months; p=0.034, q=0.245).
in three-negative dnMBC, high TMB is associated with better OS (p=0.041).
addition, genomic differences between untreated dnMBCs and primary tumors that subsequently developed into rMBCs may help to gain insight into the potential mechanisms of dnMBC metastasis potential and different therapeutic sensitivities.
variation associated with dnMBC adverse OS highlights the need for new ways to overcome underlying intrinsic resistance to current treatments.