Landscape of somatic mutations in different subtypes of advanced breast cancer with circulating tumor DNA analysis
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Updated: Feb 26, 2026
Comparative Lesions Analysis Through a Targeted Sequencing Approach
Published on: November 5, 2019
Zongbi Yi1, Fei Ma2, Chunxiao Li3
1Department of Medical Oncology, National Cancer Center/Cancer hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Abstract:
It is particularly important to provide precise therapies and understand tumor heterogeneity based on the molecular typing of mutational landscape. However, the landscape of somatic mutations in different subtypes of advanced breast cancer (ABC) is largely unknown. We applied target-region capture deep sequencing to determine the frequency and spectrum of common cancer-related gene mutations in circulating tumor DNA (ctDNA) among different ABC subtypes and analyze their association with clinical features. In this retrospective study of 100 female advanced breast cancer patients, 96 (96.0%) had somatic genomic alterations in ctDNA, including copy number variants and point mutations. The results revealed that different subtypes of ABC have distinct features in terms of genetic alterations. Multivariate regression analyses revealed that the number of somatic mutations increased with the line of endocrine therapy and the fractions of trunk mutations was positive associated with the line of target therapy.
Insights
Advanced breast cancer (ABC) subtypes exhibit distinct genetic alterations in circulating tumor DNA (ctDNA). The number of somatic mutations correlates with endocrine and target therapy lines in these patients.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Understanding tumor heterogeneity through molecular typing is crucial for precise therapies in advanced breast cancer (ABC).
- The mutational landscape across different ABC subtypes remains largely uncharacterized.
- Somatic mutations in circulating tumor DNA (ctDNA) offer a window into tumor biology.
Purpose of the Study:
- To determine the frequency and spectrum of common cancer-related gene mutations in ctDNA across diverse ABC subtypes.
- To analyze the association between these genetic alterations and clinical features.
- To elucidate the molecular basis of tumor heterogeneity in advanced breast cancer.
Main Methods:
- Retrospective study involving 100 female advanced breast cancer patients.
- Target-region capture deep sequencing of circulating tumor DNA (ctDNA).
- Analysis of somatic genomic alterations, including copy number variants and point mutations.
Main Results:
- 96% of patients (96/100) exhibited somatic genomic alterations in ctDNA.
- Distinct genetic alteration profiles were observed among different ABC subtypes.
- Increased lines of endocrine therapy correlated with a higher number of somatic mutations.
- Fractions of trunk mutations showed a positive association with the line of target therapy.
Conclusions:
- Advanced breast cancer subtypes possess unique mutational landscapes in their ctDNA.
- The accumulation of somatic mutations is influenced by the extent of endocrine and target therapy received.
- ctDNA sequencing provides valuable insights into the molecular evolution of advanced breast cancer under treatment pressure.
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