Clinical significance of plasma cell-free DNA mutations in PIK3CA, AKT1, and ESR1 gene according to treatment lines in ER-positive breast cancer

Autor: Keiichi Murakami, Yutaka Yamamoto, Hirotaka Iwase, Takashi Takeshita, Mutsuko Yamamoto-Ibusuki, Aiko Sueta, Mai Tomiguchi
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Oncology
Cancer Research
medicine.medical_specialty
Class I Phosphatidylinositol 3-Kinases
Estrogen receptor
AKT1
Breast Neoplasms
ESR1 mutations
Kaplan-Meier Estimate
Plasma cell
Biology
lcsh:RC254-282
03 medical and health sciences
Cell-free DNA
0302 clinical medicine
Breast cancer
Internal medicine
Biomarkers
Tumor
medicine
Humans
Neoplasm
Digital polymerase chain reaction
Clinical significance
Letter to the Editor
neoplasms
Estrogen Receptor alpha
DNA
Neoplasm
Prognosis
medicine.disease
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
030104 developmental biology
medicine.anatomical_structure
Cell-free fetal DNA
030220 oncology & carcinogenesis
Mutation
AKT1 mutation
Molecular Medicine
Estrogen receptor-positive breast cancer
Female
PIK3CA mutations
Cell-Free Nucleic Acids
Proto-Oncogene Proteins c-akt
Zdroj: Molecular Cancer, Vol 17, Iss 1, Pp 1-6 (2018)
Molecular Cancer
ISSN: 1476-4598
DOI: 10.1186/s12943-018-0808-y
Popis: The somatic activation of PI3K/AKT pathway mutations, PIK3CA and AKT1, and ESR1 mutations in plasma cell-free DNA (cfDNA) has been studied as a non-invasive procedure to quickly assess and monitor disease progression or therapeutic effect in breast cancer (BC) patients, but the clinical significance of these mutations in late treatment lines (TLs) remains unclear. The subjects of this study were a total of 251 plasma samples from 128 estrogen receptor-positive (ER+) BC patients. Of these plasma samples, 133 were from 73 primary BC (PBC) patients, and 118 plasma samples were from 68 metastatic BC (MBC) patients. We developed droplet digital PCR (ddPCR) assays to verify the clinical significance of PIK3CA, AKT1, and ESR1 mutations in these patients. cfDNA PIK3CA mutations were observed in 15.1% of the PBC patients, while a cfDNA AKT1 mutation was observed in 1.4% of patients, and cfDNA ESR1 mutations were observed in 2.7% of patients. Patients with detectable cfDNA PIK3CA mutations were not associated with clinical outcomes. According to the TL, the prevalence of the PIK3CA and ESR1 mutations in cfDNA were lower in early TLs compared with late TLs. In the early TL group, patients with cfDNA PIK3CA mutations had a shorter time to treatment failure (TTF) than patients without mutations (P = 0.035). However, there was no statistically significant difference between patients with or without cfDNA ESR1 mutations. However, in the late TL group, patients with cfDNA ESR1 mutations had a shorter TTF than patients without mutations (P = 0.048). However, there was no statistically significant difference between patients with or without cfDNA PIK3CA mutations. Since the prevalence of cfDNA AKT1 mutation is low in both PBC and MBC patients, the impact of AKT1 mutations on the prognosis remains unclear. We have demonstrated the difference in the clinical significance of the hotspot PIK3CA, AKT1, and ESR1 mutations in cfDNA for each TL in ER+ BC patients. Electronic supplementary material The online version of this article (10.1186/s12943-018-0808-y) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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