Inter-tumor genomic heterogeneity of breast cancers: comprehensive genomic profile of primary early breast cancers and relapses.

ABSTRACT: BACKGROUND:The breast cancer genome dynamically evolves during malignant progression and recurrence. We investigated the genomic profiles of primary early-stage breast cancers and matched relapses to elucidate the molecular underpinnings of the metastatic process, focusing on potentially actionable alterations in the recurrences. METHODS:A mono-institutional cohort of 128 patients with breast cancers (n?=?68 luminal B HER2, n?=?6 luminal B HER2+, n?=?1 HER2+ non-luminal, n?=?56 triple negative) and at least one recurrence in a timeframe of 17?years was evaluated. Next-generation sequencing comprehensive genomic profiling was performed on 289 formalin-fixed paraffin-embedded (FFPE) samples, including primary tumors and matched relapses. Correlations of genomic aberrations with clinicopathologic factors and time to breast cancer relapse were analyzed. RESULTS:Genomic data were available for 188 of 289 FFPE samples that achieved the sequencing quality parameters (failure rate 34.9%), including 106 primary tumors and 82 relapses. All primary and relapse samples harbored at least one genomic alteration, with a median number of six alterations per sample (range 1-16). The most frequent somatic genomic alterations were mutations of TP53 (primary tumors?=?49%, relapses?=?49%) and PIK3CA (primary tumors?=?33%, relapses?=?30%). Distinctive genomic alterations of primary tumors were significantly associated with molecular subtypes. TP53, PIK3R1, and NF1 somatic alterations were more frequently detected in triple negative tumors (p value

SUBMITTER: Fumagalli C 

PROVIDER: S-EPMC7566144 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature