Familial Breast Cancer is a subset of breast cancer cases that occur within specific families with a higher frequency due to some inherited mutations. Protheragen has dedicated services focused on the diagnostic and therapeutic development of familial breast cancer.
Overview of Familial Breast Cancer
Familial Breast Cancer refers to women with the condition who have one or more first- or second-degree relatives suffering from the disease. This breast cancer type has a notable inheritance factor, especially in cases where multiple family members are diagnosed early in life. The family history of breast cancer is associated with the presence of these genes which are considered to have a conservative approach to the genetic predisposition of the disease: the most known risky genes include BRCA1 and BRCA2, some moderate and many low-risk genes, as well as multiple loci identified through genome-wide association studies, known as GWAS. Even after these advancements, it is estimated that more than half of the hereditary factors linked to familial breast cancer are unknown.
Fig.1 Fraction of the excess familial risk of breast cancer explained by the currently known susceptibility genes/loci. (Wendt C.,
et al., 2019)
Pathogenesis of Familial Breast Cancer
The pathogenic mechanisms of familial breast cancer are multifaceted and involve both genetic and environmental factors. High-risk genes such as BRCA1, BRCA2, TP53, STK11, CDH1, and PTEN are known to confer a significant risk of breast cancer. These genes are involved in DNA repair, cell cycle regulation, and apoptosis. BRCA1 and BRCA2, for example, play crucial roles in homologous recombination and double-strand DNA break repair. Mutations in these genes lead to genomic instability and increased cancer risk. Moderate-risk genes like PALB2, CHEK2, and ATM also contribute to breast cancer risk. Additionally, numerous low-risk loci identified through GWAS contribute to the polygenic nature of breast cancer susceptibility.
Diagnostics Development for Familial Breast Cancer
Genetic Testing
The diagnostic development for familial breast cancer primarily involves genetic testing and risk assessment. Genetic testing includes sequencing of high-risk genes (BRCA1, BRCA2, TP53, etc.), moderate-risk genes (PALB2, CHEK2, ATM), and screening for low-risk loci identified through GWAS. Risk assessment models such as the Claus model, Gail model, BRCAPRO, and the Tyrer-Cuzick model are used to estimate the risk of developing breast cancer based on family history and genetic information. These models help in identifying individuals at high risk who may benefit from enhanced surveillance or preventive measures.
Biomarker Identification
Biomarker identification is another critical area in the diagnostics development for familial breast cancer. Biomarkers such as estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) status are essential for tailoring therapeutic strategies. Advanced techniques like next-generation sequencing (NGS) and liquid biopsies are being explored to identify novel biomarkers that can improve diagnostic accuracy and predict therapeutic response. These novel biomarkers may include genetic mutations, epigenetic modifications, and circulating biomolecules that reflect the unique biology of familial breast cancer.
Therapeutics Development for Familial Breast Cancer
- Targeted Therapies
The development of drugs and therapies for familial breast cancer includes targeted therapies, chemoprevention, and risk-reducing surgeries. Targeted therapies such as PARP inhibitors (e.g., olaparib) are being investigated for their efficacy in treating BRCA1/BRCA2 mutation carriers. These inhibitors exploit the synthetic lethality principle, where cancer cells with BRCA mutations are particularly sensitive to PARP inhibition, leading to cell death.
- Chemoprevention
Chemoprevention involves the use of drugs like tamoxifen, raloxifene, and exemestane to reduce the risk of developing breast cancer in high-risk individuals. These drugs have been shown to be effective in reducing the incidence of breast cancer in women with a strong family history or known genetic mutations.
Table 1. Therapeutics of Familial Breast Cancer.
| Therapeutics |
Drug Name |
Target |
Description |
Stage |
| Bilateral Mastectomy |
NA |
BRCA1/BRCA2 Mutation Carriers |
Reduces the risk of breast cancer by approximately 90%. |
Approved |
| Bilateral Salpingo-Oophorectomy (BSO) |
NA |
BRCA1/BRCA2 Mutation Carriers |
If done before age 45, it can reduce the risk of ovarian cancer by 80-90% and the risk of breast cancer by 50%. |
Approved |
| Chemoprevention |
Tamoxifen |
Estrogen Receptor (ER) |
Reduces the risk of developing breast cancer in high-risk individuals. |
Approved |
| Chemoprevention |
Exemestane |
Aromatase |
Reduces the risk of breast cancer in postmenopausal women. |
Approved |
| Targeted Therapy |
PARP Inhibitors |
BRCA1/BRCA2 Mutation Carriers |
Exploits synthetic lethality in BRCA1/BRCA2-deficient cells, leading to apoptosis. |
Preclinical |
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 a comprehensive suite of services for the diagnostics and therapeutics development of FBC. Our services encompass genetic testing, risk prediction modeling, biomarker discovery, targeted therapy development, immunotherapy research, and combination therapy optimization.
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
- Patient-Derived Organoid Models
- TP53 Genetic Engineering Models
- STK11 Genetic Engineering Models
- CDH1 Genetic Engineering Models
Protheragen recognizes that every preclinical development project for familial breast cancer presents unique challenges and requirements. To address this, Protheragen offers highly customizable services, allowing clients to tailor research programs precisely to their specific needs and objectives. If you are interested in our services, please feel free to contact us.
References
- Wendt, Camilla, and Sara Margolin. "Identifying breast cancer susceptibility genes–a review of the genetic background in familial breast cancer." Acta Oncologica 58.2 (2019): 135-146.
- Lalloo, F., and D. G. Evans. "Familial breast cancer." Clinical genetics 82.2 (2012): 105-114.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
