Genetic Alterations Detected by Circulating Tumor DNA in HER2-Low Metastatic Breast Cancer.
Clin Cancer Res
; 29(16): 3092-3100, 2023 08 15.
Article
em En
| MEDLINE
| ID: mdl-37265453
ABSTRACT
PURPOSE:
About 50% of breast cancers are defined as HER2-low and may benefit from HER2-directed antibody-drug conjugates. While tissue sequencing has evaluated potential differences in genomic profiles for patients with HER2-low breast cancer, genetic alterations in circulating tumor DNA (ctDNA) have not been well described. EXPERIMENTALDESIGN:
We retrospectively analyzed 749 patients with metastatic breast cancer (MBC) and ctDNA evaluation by Guardant360 from three academic medical centers. Tumors were classified as HER2-low, HER2-0 (IHC 0) or HER2-positive. Single-nucleotide variants, copy-number variants, and oncogenic pathways were compared across the spectrum of HER2 expression. Overall survival (OS) was evaluated by HER2 status and according to oncogenic pathways.RESULTS:
Patients with HER2-low had higher rates of PIK3CA mutations [relative risk ratio (RRR), 1.57; P = 0.024] compared with HER2-0 MBC. There were no differences in ERBB2 alterations or oncogenic pathways between HER2-low and HER2-0 MBC. Patients with HER2-positive MBC had more ERBB2 alterations (RRR, 12.43; P = 0.002 for amplification; RRR, 3.22; P = 0.047 for mutations, in the hormone receptor-positive cohort), fewer ERS1 mutations (RRR, 0.458; P = 0.029), and fewer ER pathway alterations (RRR, 0.321; P < 0.001). There was no difference in OS for HER2-low and HER2-0 MBC [HR, 1.01; 95% confidence interval (CI), 0.79-1.29], while OS was improved in HER2-positive MBC (HR, 0.32; 95% CI, 0.21-0.49; P < 0.001).CONCLUSIONS:
We observed a higher rate of PIK3CA mutations, but no significant difference in ERBB2 alterations, oncogenic pathways, or prognosis, between patients with HER2-low and HER2-0 MBC. If validated, our findings support the conclusion that HER2-low MBC does not represent a unique biological subtype.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
DNA Tumoral Circulante
Tipo de estudo:
Etiology_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
Idioma:
En
Revista:
Clin Cancer Res
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2023
Tipo de documento:
Article