TP53 and/or BRCA1 Mutations Based on CtDNA Analysis as Prognostic Biomarkers for Primary Triple-Negative Breast Cancer

• Published in: Cancers Vol. 16; no. 6; p. 1184
• Main Authors: Arimura, Akiko, Sakai, Kazuko, Kaneshiro, Kazuhisa, Morisaki, Takafumi, Hayashi, Saori, Mizoguchi, Kimihisa, Yamada, Mai, Kai, Masaya, Ono, Mayumi, Nishio, Kazuto, Nakamura, Masafumi, Kubo, Makoto
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 18-03-2024; MDPI
• Subjects: Apoptosis; Biomarkers; Biopsy; BRCA1 protein; BRCA2 protein; Breast cancer; Cancer therapies; Cell death; Chemotherapy; Clinical medicine; Disease; Drug development; Gene amplification; Genomes; Laboratories; Medical prognosis; Metastasis; Mutation; Next-generation sequencing; p53 Protein; Patients; Plasma; Prognosis; Surgery; Therapeutic targets; Tumors; United States > US; Japan; triple-negative breast cancer; BRCA1; TP53; ctDNA
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers16061184

Precise biomarkers for predicting the therapeutic efficacy of molecularly targeted drugs are limited at the protein level; thus, it has been important to broadly scrutinize individual cancer driver gene mutations for effective cancer treatments. Multiplex cancer genome profiling can comprehensively identify gene mutations that are therapeutic targets using next-generation sequencing (NGS). In addition, circulating tumor DNA (ctDNA) is a DNA fragment released into the blood by tumor cell-derived cell death or apoptosis. Liquid biopsy with ctDNA is a novel clinical test for identifying genetic mutations in an entire population noninvasively, in real-time, and heterogeneously. Although there are several reports on ctDNA, fewer have evaluated ctDNA with NGS before an initial treatment for breast cancer patients. Therefore, we examined whether analyzing tumor-associated gene mutations in primary breast cancer based on ctDNA could serve as a biomarker for prognosis and optimal treatment selection. Ninety-five primary breast cancer patients treated at our department from January 2017 to October 2020 were included. Pretreatment plasma samples were subjected to NGS analysis of ctDNA, and correlations with patients' clinicopathological characteristics were evaluated. Fifty-nine (62.1%) patients were positive for ctDNA. ctDNA tended to be positive in hormone receptor-negative, and
(34%),
(20%), and
(17%) gene mutations were more frequent. Regarding recurrence-free survival, the prognosis was poor in the
and/or
mutation-positive groups, especially in triple-negative breast cancer (TNBC) patients. In conclusion, the results of this study indicate that ctDNA with liquid biopsy could identify the poor prognosis group before treatment among TNBC patients and for those for whom optimal treatment selection is desirable; additionally, optimal treatment could be selected according to the ctDNA analysis results.