Related Experiment Video
Updated: Jul 9, 2025
Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
Published on: December 9, 2015
Genomic Characteristics and Its Therapeutic Implications in Breast Cancer Patients with Detectable Molecular Residual
Shu Zhang1, Yan Jiang1, Lu Zhou1
1Department of Breast and Thyroid Surgery, Daping Hospital, Army Military Medical University, Chongqing, China.
Purpose:
Molecular residual disease (MRD) is the main cause of postoperative recurrence of breast cancer. However, the baseline tumor genomic characteristics and therapeutic implications of breast cancer patients with detectable MRD after surgery are still unknown.
Materials And Methods:
In this study, we enrolled 80 patients with breast cancer who underwent next-generation sequencing-based genetic testing of 1,021 cancer-related genes performed on baseline tumor and postoperative plasma, among which 18 patients had detectable MRD after surgery.
Results:
Baseline clinical characteristics found that patients with higher clinical stages were more likely to have detectable MRD. Analysis of single nucleotide variations and small insertions/deletions in baseline tumors showed that somatic mutations in MAP3K1, ATM, FLT1, GNAS, POLD1, SPEN, and WWP2 were significantly enriched in patients with detectable MRD. Oncogenic signaling pathway analysis revealed that alteration of the Cell cycle pathway was more likely to occur in patients with detectable MRD (p=0.012). Mutational signature analysis showed that defective DNA mismatch repair and activation-induced cytidine deaminase (AID) mediated somatic hypermutation (SHM) were associated with detectable MRD. According to the OncoKB database, 77.8% (14/18) of patients with detectable MRD had U.S. Food and Drug Administration-approved mutational biomarkers and targeted therapy.
Conclusion:
Our study reports genomic characteristics of breast cancer patients with detectable MRD. The cell cycle pathway, defective DNA mismatch repair, and AID-mediated SHM were found to be the possible causes of detectable MRD. We also found the vast majority of patients with detectable MRD have the opportunity to access targeted therapy.
Insights
Detecting molecular residual disease (MRD) after breast cancer surgery is linked to specific genomic alterations, including cell cycle pathway changes and DNA repair defects. Many patients with MRD can still access targeted therapies.
Area of Science:
- Oncology
- Genomics
- Cancer Recurrence
Background:
- Molecular residual disease (MRD) is a primary driver of postoperative breast cancer recurrence.
- Genomic factors influencing MRD and their therapeutic relevance remain largely unexplored.
Purpose of the Study:
- To investigate the baseline tumor genomic characteristics of breast cancer patients with detectable MRD post-surgery.
- To explore the therapeutic implications for these patients.
Main Methods:
- Next-generation sequencing of 1,021 cancer-related genes was performed on baseline tumor and postoperative plasma samples from 80 breast cancer patients.
- Eighteen patients with detectable MRD were identified for further genomic analysis.
Main Results:
- Higher clinical stage was associated with detectable MRD.
- Somatic mutations in genes including MAP3K1, ATM, and FLT1 were enriched in patients with MRD.
- Alterations in the cell cycle pathway, defective DNA mismatch repair, and activation-induced cytidine deaminase (AID)-mediated somatic hypermutation (SHM) were linked to MRD.
- 77.8% of MRD-positive patients had FDA-approved biomarkers for targeted therapy.
Conclusions:
- Specific genomic features, such as cell cycle pathway alterations and DNA repair defects, are associated with detectable MRD in breast cancer.
- The majority of patients with detectable MRD are candidates for targeted therapy, highlighting the importance of genomic profiling.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:56Treatment Resistant Cancers
02:38Mitogens and the Cell Cycle