Inter-tumor genomic heterogeneity of breast cancers: comprehensive genomic profile of primary early breast cancers and relapses.
Breast Cancer Res
; 22(1): 107, 2020 10 15.
Article
em En
| MEDLINE
| ID: mdl-33059724
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 < 0.05); CCND1, FGF3, and FGFR1 copy number gains were recurrently identified in luminal cases (p value < 0.05). Moreover, TP53 mutations and MYC amplification were significantly and independently associated with a shorter time to relapse (p value < 0.05). Molecular subtype changes between primary tumors and relapses were seen in 10 of 128 (7.8%) cases. Most driver genomic alterations (55.8%) were shared between primary tumors and matched recurrences. However, in 39 of 61 cases (63.9%), additional private alterations were detected in the relapse samples only, including 12 patients with potentially actionable aberrations.CONCLUSIONS:
Specific genomic aberrations of primary breast cancers were associated with time to relapse. Primary tumors and matched recurrences showed a core of shared driver genomic aberrations but private actionable alterations have been identified in the relapses.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Biomarcadores Tumorais
/
Genômica
/
Terapia de Alvo Molecular
/
Mutação
/
Recidiva Local de Neoplasia
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Aged
/
Female
/
Humans
/
Middle aged
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article