TP53 and/or BRCA1 Mutations Based on CtDNA Analysis as Prognostic Biomarkers for Primary Triple-Negative Breast
Akiko Arimura1,2, Kazuko Sakai3, Kazuhisa Kaneshiro2
1Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Abstract:
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 TP53 (34%), BRCA1 (20%), and BRCA2 (17%) gene mutations were more frequent. Regarding recurrence-free survival, the prognosis was poor in the TP53 and/or BRCA1 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.
Insights
Liquid biopsy using circulating tumor DNA (ctDNA) can identify high-risk breast cancer patients before treatment. Analyzing ctDNA mutations like TP53 and BRCA1 aids in prognosis and selecting optimal therapies, especially for triple-negative breast cancer.
Area of Science:
- Oncology
- Genetics
- Molecular Diagnostics
Background:
- Protein-level biomarkers for targeted cancer drug efficacy are limited.
- Multiplex cancer genome profiling with next-generation sequencing (NGS) identifies therapeutic gene targets.
- Circulating tumor DNA (ctDNA) offers noninvasive, real-time detection of tumor mutations via liquid biopsy.
Purpose of the Study:
- To evaluate ctDNA analysis with NGS as a prognostic biomarker in primary breast cancer.
- To determine if ctDNA can guide optimal treatment selection before initial therapy.
- To assess the correlation between ctDNA mutations and clinicopathological characteristics.
Main Methods:
- NGS analysis of pretreatment plasma ctDNA from 95 primary breast cancer patients.
- Evaluation of ctDNA positivity rates and common gene mutations (TP53, BRCA1, BRCA2).
- Correlation analysis of ctDNA findings with recurrence-free survival and clinicopathological data.
Main Results:
- 62.1% of patients were ctDNA-positive.
- ctDNA positivity was more frequent in hormone receptor-negative breast cancer.
- TP53 (34%), BRCA1 (20%), and BRCA2 (17%) mutations were common.
- TP53 and/or BRCA1 mutations correlated with poor prognosis, particularly in triple-negative breast cancer (TNBC).
Conclusions:
- ctDNA liquid biopsy can identify patients with poor prognosis before treatment, especially in TNBC.
- ctDNA analysis can inform optimal treatment selection for breast cancer patients.
- This approach provides a valuable tool for personalized cancer therapy.
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