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Analysis of circulating tumor DNA to monitor metastatic breast cancer.
Literature Information
| DOI | 10.1056/NEJMoa1213261 |
|---|---|
| PMID | 23484797 |
| Journal | The New England journal of medicine |
| Impact Factor | 78.5 |
| JCR Quartile | Q1 |
| Publication Year | 2013 |
| Times Cited | 1121 |
| Keywords | circulating tumor DNA, metastatic breast cancer, biomarkers |
| Literature Type | Comparative Study, Journal Article, Research Support, Non-U.S. Gov't |
| ISSN | 0028-4793 |
| Pages | 1199-209 |
| Issue | 368(13) |
| Authors | Sarah-Jane Dawson, Dana W Y Tsui, Muhammed Murtaza, Heather Biggs, Oscar M Rueda, Suet-Feung Chin, Mark J Dunning, Davina Gale, Tim Forshew, Betania Mahler-Araujo, Sabrina Rajan, Sean Humphray, Jennifer Becq, David Halsall, Matthew Wallis, David Bentley, Carlos Caldas, Nitzan Rosenfeld |
TL;DR
This study investigates the effectiveness of circulating tumor DNA (ctDNA) as a biomarker for monitoring treatment response in metastatic breast cancer, comparing it with traditional markers like CA 15-3 and circulating tumor cells. The findings demonstrate that ctDNA detection was significantly higher (97%) and more correlated with changes in tumor burden, providing earlier indicators of treatment response, highlighting its potential as a superior biomarker in clinical settings.
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circulating tumor DNA · metastatic breast cancer · biomarkers
Abstract
BACKGROUND The management of metastatic breast cancer requires monitoring of the tumor burden to determine the response to treatment, and improved biomarkers are needed. Biomarkers such as cancer antigen 15-3 (CA 15-3) and circulating tumor cells have been widely studied. However, circulating cell-free DNA carrying tumor-specific alterations (circulating tumor DNA) has not been extensively investigated or compared with other circulating biomarkers in breast cancer.
METHODS We compared the radiographic imaging of tumors with the assay of circulating tumor DNA, CA 15-3, and circulating tumor cells in 30 women with metastatic breast cancer who were receiving systemic therapy. We used targeted or whole-genome sequencing to identify somatic genomic alterations and designed personalized assays to quantify circulating tumor DNA in serially collected plasma specimens. CA 15-3 levels and numbers of circulating tumor cells were measured at identical time points.
RESULTS Circulating tumor DNA was successfully detected in 29 of the 30 women (97%) in whom somatic genomic alterations were identified; CA 15-3 and circulating tumor cells were detected in 21 of 27 women (78%) and 26 of 30 women (87%), respectively. Circulating tumor DNA levels showed a greater dynamic range, and greater correlation with changes in tumor burden, than did CA 15-3 or circulating tumor cells. Among the measures tested, circulating tumor DNA provided the earliest measure of treatment response in 10 of 19 women (53%).
CONCLUSIONS This proof-of-concept analysis showed that circulating tumor DNA is an informative, inherently specific, and highly sensitive biomarker of metastatic breast cancer. (Funded by Cancer Research UK and others.).
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Primary Questions Addressed
- What are the potential advantages of using circulating tumor DNA over traditional biomarkers like CA 15-3 and circulating tumor cells in monitoring treatment response?
- How might the findings regarding circulating tumor DNA impact future research directions in the field of metastatic breast cancer?
- In what ways could personalized assays for circulating tumor DNA be optimized to improve sensitivity and specificity in clinical settings?
- What are the implications of the dynamic range of circulating tumor DNA levels for early detection of treatment resistance in metastatic breast cancer?
- How does the identification of somatic genomic alterations in circulating tumor DNA contribute to the development of targeted therapies for breast cancer patients?
Key Findings
Research Background and Objectives
The literature presents a variety of recent studies across different fields of science, including medicine, immunology, microbiology, and bioengineering. The main objective of these studies is to advance our understanding of various biological processes, improve diagnostic methods, and develop new materials with enhanced properties.
Main Methods/Materials/Experimental Design
The studies employ diverse methodologies tailored to their specific research questions. Below is a summary of the key methods used in selected studies:
| Study Focus | Methods/Materials Used |
|---|---|
| Blood Test for Cancer DNA | - Identification of genetic markers in blood samples from patients. - Comparison of sensitivity with traditional tests for circulating tumor cells. |
| Flu Vaccines and Immune Response | - Injection of flu vaccines into adults and children. - Tracking immune cell activation over time. |
| Mobile Worm Microscope | - Development of a smartphone-based microscope. - Analysis of stool samples for intestinal worm detection. |
| DNA Protection in Silica | - Encapsulation of DNA in silica particles and testing against UV radiation and chemicals. |
Technical Workflow Visualization
Key Results and Findings
- Blood Test for Cancer DNA: The study found that the detection of tumor DNA in blood was more sensitive than existing methods, suggesting its potential for non-invasive cancer monitoring.
- Flu Vaccines: The research identified a specific class of immune cells that enhance antibody production, revealing age-related differences in vaccine effectiveness.
- Mobile Worm Microscope: The smartphone microscope successfully identified over 60% of worm-free samples and nearly 70% of samples with eggs, demonstrating its potential for field diagnostics.
- DNA Protection: Encapsulated DNA remained largely undamaged after exposure to extreme conditions, indicating a promising method for DNA preservation.
Main Conclusions/Significance/Innovation
- The studies highlight significant advancements in non-invasive diagnostic techniques and innovative material applications.
- The findings on cancer DNA monitoring could lead to quicker and less invasive diagnostic protocols.
- Understanding immune responses to vaccines can inform better vaccination strategies, particularly for vulnerable populations like children.
- The development of portable diagnostic tools like the smartphone microscope represents a leap in accessibility for medical diagnostics in low-resource settings.
Research Limitations and Future Directions
- Blood Test for Cancer DNA: Further validation in larger, diverse cohorts is needed to confirm findings and assess clinical applicability.
- Flu Vaccines: More research is necessary to explore the implications of immune cell activation on vaccine efficacy across different demographics.
- Mobile Worm Microscope: The need for higher-resolution imaging to improve diagnostic accuracy is emphasized.
- DNA Protection: Future studies should explore the long-term stability of encapsulated DNA under various environmental conditions.
In conclusion, these studies collectively underscore the importance of innovative approaches in biomedical research and the potential for translating these findings into practical applications that could significantly enhance healthcare outcomes.
Literatures Citing This Work
- Breast cancer: Circulating tumour DNA the better of the blood biomarkers. - Rebecca Kirk - Nature reviews. Clinical oncology (2013)
- Genomic profiling defines subtypes of prostate cancer with the potential for therapeutic stratification. - Jamie R Schoenborn;Pete Nelson;Min Fang - Clinical cancer research : an official journal of the American Association for Cancer Research (2013)
- iPOP goes the world: integrated personalized Omics profiling and the road toward improved health care. - Jennifer Li-Pook-Than;Michael Snyder - Chemistry & biology (2013)
- Circulating tumour cells and cell-free DNA as tools for managing breast cancer. - Leticia De Mattos-Arruda;Javier Cortes;Libero Santarpia;Ana Vivancos;Josep Tabernero;Jorge S Reis-Filho;Joan Seoane - Nature reviews. Clinical oncology (2013)
- Tracking tumor resistance using 'liquid biopsies'. - Klaus Pantel;Luis A Diaz;Kornelia Polyak - Nature medicine (2013)
- Monitor tumor burden with circulating tumor DNA. - William D Figg;Jim Reid - Cancer biology & therapy (2013)
- Biopsies: next-generation biospecimens for tailoring therapy. - Mark Basik;Adriana Aguilar-Mahecha;Caroline Rousseau;Zuanel Diaz;Sabine Tejpar;Alan Spatz;Celia M T Greenwood;Gerald Batist - Nature reviews. Clinical oncology (2013)
- Genetic heterogeneity in breast cancer: the road to personalized medicine? - Richard D Baird;Carlos Caldas - BMC medicine (2013)
- Circulating Methylated XAF1 DNA Indicates Poor Prognosis for Gastric Cancer. - Zhi-Qiang Ling;Ping Lv;Xiao-Xiao Lu;Jiang-Liu Yu;Jing Han;Li-Sha Ying;Xin Zhu;Wang-Yu Zhu;Xian-Hua Fang;Shi Wang;Yi-Chen Wu - PloS one (2013)
- Liquid biopsy: monitoring cancer-genetics in the blood. - Emily Crowley;Federica Di Nicolantonio;Fotios Loupakis;Alberto Bardelli - Nature reviews. Clinical oncology (2013)
... (1111 more literatures)
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