BRCA2-associated breast cancer is a subtype of hereditary breast cancer linked to mutations in the BRCA2 gene. Protheragen offers comprehensive preclinical therapeutics development services tailored to BRCA2-associated breast cancer. Our services encompass genetic testing, biomarker development, drug discovery, and preclinical efficacy testing.
Overview of BRCA2-associated Breast Cancer
BRCA2-associated breast cancer is a subset of hereditary breast cancers linked to germline mutations in the BRCA2 gene. These mutations impair the cell's ability to repair DNA damage via homologous recombination, leading to genomic instability and an increased risk of developing breast cancer. BRCA2-associated tumors are often high-grade, with distinct histological features such as less tubular structure and higher mitotic counts compared to sporadic breast cancers. Additionally, these tumors frequently express higher levels of estrogen and progesterone receptors, influencing therapeutic strategies.
Fig.1 Kaplan-Meier plot of survival from the time of first locoregional recurrence or metastasis according to BRCA mutation status. (Song Y.,
et al., 2020)
Pathogenesis of BRCA2-associated Breast Cancer
The pathogenesis of BRCA2-associated breast cancer is rooted in the critical role of BRCA2 in DNA repair. BRCA2 is essential for homologous recombination-mediated repair of double-strand DNA breaks. Mutations in BRCA2 disrupt this repair mechanism, leading to genomic instability and an increased likelihood of malignant transformation. This genetic instability is compounded by the frequent expression of hormone receptors, which can drive tumor growth. Furthermore, BRCA2-associated tumors often present at more advanced stages, with a higher incidence of bilateral disease, contributing to poorer prognosis.
Diagnostics Development for BRCA2-associated Breast Cancer
- Genetic Testing: Genetic testing is the cornerstone of diagnosing BRCA2-associated breast cancer. It involves sequencing the BRCA2 gene to identify pathogenic mutations. This testing is typically recommended for individuals with a strong family history of breast or ovarian cancer, early-onset breast cancer, or bilateral breast cancer. Next-generation sequencing (NGS) technologies have revolutionized genetic testing by enabling high-throughput, cost-effective sequencing of multiple genes simultaneously.
- Biomarker Development: Biomarkers are crucial for the early detection, prognosis, and monitoring of BRCA2-associated breast cancer. Research is ongoing to identify novel biomarkers that can predict response to therapy, monitor disease progression, and detect recurrence.
Therapeutics of BRCA2-associated Breast Cancer
| Therapeutics |
Drug Name |
Target |
Description |
Stage |
| Chemotherapy |
Anthracyclines |
Induction of indirect double-strand DNA breaks (DSBs) by inhibiting topoisomerases and causing DNA interstrand cross-links and free radical generation |
Therapeutic with (neo)adjuvant chemotherapy, including anthracyclines, causes cell damage by inducing DNA breaks. Given that BRCA1 and BRCA2 proteins play a role in DNA damage repair, the efficacy of (neo)adjuvant chemotherapy may be increased in BRCA1/2-associated breast cancer patients. Several clinical studies have shown increased sensitivity for anthracycline-containing chemotherapy in BRCA1/2 mutation carriers. |
Approved |
| Chemotherapy |
Taxanes |
(Implied) Induction of DNA damage |
Taxanes are also used in (neo)adjuvant chemotherapy for breast cancer. The study found no significant difference in the relative total dose intensity (RTDI) for taxanes between BRCA1/2-associated and sporadic breast cancer groups. Acute chemotherapy-related toxicity was not different between BRCA1/2-associated and sporadic breast cancer patients, suggesting that the DNA damage repair mechanism in non-cancer cells with one normal copy of BRCA1 or BRCA2 is sufficient to handle acute toxicity. |
Approved |
| Chemotherapy |
Carboplatin |
Strong inducer of double-strand DNA breaks (DSBs) |
Platinum derivatives like carboplatin showed higher efficacy in BRCA1/2-associated breast cancer patients compared to sporadic breast cancer patients. This is attributed to the lack of functional BRCA1 or BRCA2 protein in these tumor cells, making them more susceptible to therapeutics that cause DSBs. |
Approved |
| Chemotherapy |
Cisplatin |
Strong inducer of double-strand DNA breaks (DSBs) |
Platinum derivatives like cisplatin showed higher efficacy in BRCA1/2-associated breast cancer patients compared to sporadic breast cancer patients. This is due to BRCA1 and BRCA2 proteins being essential in the repair of DSBs by homologous recombination, thus, therapeutics causing DSBs are more effective in tumor cells lacking functional BRCA1/2 proteins. |
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 diagnostics and therapeutics development services for BRCA2-associated breast cancer. Our services encompass genetic testing, pathological examination, and molecular profiling to provide a holistic approach to diagnosis. In therapeutics development, we specialize in optimizing chemotherapy regimens, developing targeted therapies, evaluating hormonal therapeutics, and exploring immunotherapeutic strategies.
Diagnostics Development
- Karyotype Analysis Service
- Omics Analysis Service
- Biomarker Development Service
- Artificial Intelligence Service
Therapeutic Development
- Anticancer Peptide
- Gene Therapy
- Immunotherapy
- Monoclonal Antibody
- Phytotherapy
- Small Molecule Drug
- Therapeutic Cancer Vaccine
Disease Models
- MCF7 Cell Culture Models
- T47D Cell Culture Models
- Genetically Engineered Mouse Organoids
- WAP-Cre and MMTV-Cre Mouse Models
- Patient-Derived Xenograft (PDX) Models
Protheragen's diagnostics and therapeutics development services are characterized by our commitment to innovation, precision, and excellence. We employ cutting-edge technologies and methodologies to deliver accurate and reliable results. If you are interested in our services, please feel free to contact us.
References
- Song, Yun, et al. "Patterns of recurrence and metastasis in BRCA1/BRCA2‐associated breast cancers." Cancer 126.2 (2020): 271-280.
- Petrucelli, Nancie, Mary B. Daly, and Tuya Pal. "BRCA1-and BRCA2-associated hereditary breast and ovarian cancer." (2022).
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
