BRCA1-associated breast cancer is a subtype of breast cancer characterized by mutations in the BRCA1 gene, which plays a crucial role in DNA repair mechanisms. Protheragen offers comprehensive preclinical therapeutics development services tailored to BRCA1-associated breast cancer.
Overview of BRCA1-associated Breast Cancer
BRCA1-associated breast cancer is a distinct subtype of breast cancer that arises in individuals harboring pathogenic variants in the BRCA1 gene. These variants confer a significantly elevated risk of developing breast cancer, with cumulative risks reaching up to 87% by the age of 70. This cancer type is often characterized by a triple-negative phenotype, marked by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. Additionally, BRCA1-associated tumors frequently exhibit a basal-like molecular subtype, characterized by the expression of basal cell markers. These features are associated with aggressive histopathological characteristics and relatively poor patient outcomes.
Fig.1 Curated gene sets linked to BRCA1-associated breast cancer risk and expression correlation with candidate modifier
HMMR. (Mateo F.,
et al., 2022)
Pathogenesis of BRCA1-associated Breast Cancer
The pathogenesis of BRCA1-associated breast cancer is primarily driven by the loss of function of the BRCA1 gene, which plays a crucial role in DNA repair and maintenance of genomic stability. BRCA1 is involved in homologous recombination repair, a process essential for repairing double-strand DNA breaks. When BRCA1 is mutated, cells are more likely to accumulate genetic errors, leading to genomic instability. This instability can result in the activation of oncogenes and the inactivation of tumor suppressor genes, ultimately promoting cancer development. Additionally, BRCA1-associated breast cancers often exhibit high levels of genomic instability, epithelial-to-mesenchymal transition (EMT), and tissue infiltration of tumor-associated macrophages.
Diagnostics Development for BRCA1-associated Breast Cancer
Genetic Testing
Genetic testing is a cornerstone of diagnosing BRCA1-associated breast cancer. This involves sequencing the BRCA1 gene to identify pathogenic variants. Next-generation sequencing (NGS) technologies have revolutionized genetic testing, allowing for rapid and accurate identification of mutations. For example, whole-exome sequencing can detect both known and novel BRCA1 mutations, providing comprehensive insights into the genetic landscape of the tumor.
Molecular Profiling
Molecular profiling involves analyzing the expression of specific genes and proteins in tumor samples. This can include immunohistochemistry (IHC) to detect the expression of basal cell markers and other proteins associated with BRCA1-associated breast cancer. Additionally, RNA sequencing (RNA-seq) can be used to profile the transcriptome of tumors, identifying differentially expressed genes that may serve as diagnostic markers.
Therapeutics Development for BRCA1-associated Breast Cancer
- Targeted Therapies
Targeted therapies aim to inhibit specific molecular pathways that are dysregulated in BRCA1-associated breast cancer. For example, inhibitors of the AURKA kinase, which is often overexpressed in these tumors, are being explored as potential therapeutic agents. These targeted therapies can provide more precise therapeutic options with fewer side effects compared to traditional chemotherapy.
- Immunotherapy
Given the high level of genomic instability and immune cell infiltration observed in BRCA1-associated breast cancers, immunotherapies such as immune checkpoint inhibitors are being investigated as potential therapeutics. These therapies aim to enhance the immune system's ability to recognize and attack cancer cells, offering a promising approach for improving outcomes.
Table 1. Therapeutics of BRCA1-associated Breast Cancer.
| Therapeutics |
Drug Name |
Target |
Description |
Stage |
| PARP Inhibitors |
Olaparib |
PARP enzyme |
Induces cell death by interfering with DNA replication; approved for some indications; ongoing trials for combinations |
Approved |
| PARP Inhibitors |
Talazoparib |
PARP enzyme |
Improves progression-free survival and tumor response rates; first targeted therapeutic for advanced BRCA-mutated breast cancer |
Approved |
| Chemotherapy |
Docetaxel and Paclitaxel |
Microtubules |
Microtubule stabilizing agents that block cell proliferation; less sensitivity in BRCA1 mutation carriers with hormone-negative cancers |
Approved |
| Chemotherapy |
Cisplatin and Carboplatin |
DNA |
Bind to DNA, forming adducts that cause DNA damage; BRCA1 mutation carriers are highly sensitive |
Approved |
| Hormone Therapy |
Tamoxifen |
Estrogen receptor |
Reduces the risk of contralateral tumors in hormone receptor-positive breast cancer with BRCA1 mutations; mixed results in preventive benefit |
Approved |
| Hormone Therapy |
Aromatase Inhibitors |
Aromatase enzyme |
Essential for hormone receptor-positive breast cancer with BRCA1 mutations to delay progression and prevent contralateral tumors |
Approved |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen offers comprehensive services for the development of diagnostics and therapeutics for BRCA1-associated breast cancer. Our services encompass genetic testing, molecular profiling, and advanced imaging techniques to provide accurate and comprehensive diagnostic solutions. Additionally, we specialize in the development of targeted therapies, PARP inhibitors, and immunotherapies, leveraging cutting-edge research and expertise to advance therapeutics development for this challenging cancer subtype.
- Karyotype Analysis Service
- Omics Analysis Service
- Biomarker Development Service
- Artificial Intelligence Service
- Customized Diagnostics Development
- Anticancer Peptide
- Gene Therapy
- Immunotherapy
- Monoclonal Antibody
- Phytotherapy
- Small Molecule Drug
- Therapeutic Cancer Vaccine
- Conventional BRCA1 Mouse Models
- Conditional BRCA1 Models Carrying BRCA1 Truncation Alleles
- Conditional BRCA1 Models Carrying Large BRCA1 Deletions
- Conditional BRCA1 Models on a Pgp1-Deficient
Protheragen's preclinical research services are designed to support the development of novel diagnostics and therapeutics for BRCA1-associated breast cancer. Our services include the use of advanced mouse models and cell lines to investigate the efficacy and mechanism of action of new drugs. If you are interested in our services, please feel free to contact us.
References
- Mateo, Francesca, et al. "Modification of BRCA1-associated breast cancer risk by HMMR overexpression." Nature communications 13.1 (2022): 1895.
- Brekelmans, C. T. M., et al. "Survival and prognostic factors in BRCA1-associated breast cancer." Annals of oncology 17.3 (2006): 391-400.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
