Association between FGFR1 copy numbers, MAP3K1 mutations, and survival in axillary node-positive, hormone receptor-positive, and HER2-negative early breast cancer in the PACS04 and METABRIC studies.
Breast Cancer Res Treat
; 179(2): 387-401, 2020 Jan.
Article
en En
| MEDLINE
| ID: mdl-31620934
ABSTRACT
PURPOSE:
Hormone receptor-positive (HR+) and human epidermal growth factor receptor 2 negative (HER2-) early breast cancer (BC) is the most prevalent BC subtype with substantial biological heterogeneity. Although clinicopathological (CP) characteristics have a clear prognostic value, additional biomarkers could refine survival prediction and guide treatment decision.METHODS:
Copy number aberrations and somatic driver mutations were obtained with OncoScan CGH array and sequencing of 36 genes on HR+/HER2- node-positive early BC patients treated with chemotherapy from the PACS04 trial. We built a two-gene genomic score (GS) associated with distant disease-free survival (DDFS), whose prognostic value was assessed on the external METABRIC data (n = 1413) using overall survival (OS) and breast cancer-specific survival (BCSS).RESULTS:
In the PACS04 trial (n = 327), the median follow-up for DDFS (65 events) was 9.6 years. FGFR1 amplifications ([Formula see text] = 2.44, 95% CI [1.25; 4.76], p = 0.009) and MAP3K1 mutations ([Formula see text] = 0.10, [0.01; 0.78], p = 0.03) were associated with DDFS beyond CP characteristics. A prognostic GS combining FGFR1 amplifications and MAP3K1 mutations added more information to CP model ([Formula see text] = 12.97, [Formula see text] < 0.001 and [Formula see text] = 11.52, [Formula see text] < 0.001). In the METABRIC study (n = 1413), FGFR1 amplifications ([Formula see text] = 2.00 [1.40; 2.87], p < 0.001) and MAP3K1 mutations ([Formula see text] = 0.58 [0.41; 0.83], p = 0.003) were significantly associated with BCSS beyond CP characteristics. The prognostic GS added significant prognostic information to CP model ([Formula see text] = 15.39, [Formula see text] < 0.001 and [Formula see text] = 5.62, [Formula see text] = 0.02).CONCLUSION:
In axillary node-positive, HR+, and HER2- early BC, amplifications of FGFR1 gene were strongly associated with increased risk for distant disease, while mutations of MAP3K1 gene were significantly associated with decreased risk.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
/
Biomarcadores de Tumor
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Quinasa 1 de Quinasa de Quinasa MAP
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Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos
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Variaciones en el Número de Copia de ADN
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Mutación
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
Breast Cancer Res Treat
Año:
2020
Tipo del documento:
Article
País de afiliación:
Francia