From the Guidelines
Individuals with a BRCA1 gene mutation should undergo enhanced cancer screening, including annual breast MRI and mammograms starting at age 25, and consider risk-reducing salpingo-oophorectomy (RRSO) by age 35-40 to substantially reduce the risk of ovarian and breast cancers. The presence of a BRCA1 mutation greatly increases the risk of childhood cancers and manifests with the clinical picture of Fanconi anemia type D1 1. According to the European Society for Medical Oncology (ESMO) and National Comprehensive Cancer Network (NCCN) guidelines, women with BRCA1 mutations should be counseled regarding breast awareness and breast self-exam starting at age 18, and undergo clinical breast exam and imaging with a combination of mammography and magnetic resonance imaging (MRI) annually from age 25 1.
Key considerations for management include:
- Risk-reducing salpingo-oophorectomy (RRSO) by age 35-40, which substantially reduces the risk of ovarian cancer and significantly reduces breast cancer risk if carried out before menopause 1
- Prophylactic mastectomy may also be considered due to the high lifetime cancer risk and increased risk of secondary breast cancers 1
- Tamoxifen may reduce the risk of ER-positive breast cancer in women with a BRCA1 mutation who have not undergone prophylactic oophorectomy before menopause, although the evidence is limited 1
- Oral contraceptives may decrease the risk of ovarian cancer in BRCA1 mutation carriers, but have no significant impact on breast cancer risk 1
It is crucial to recognize individuals with a hereditary cancer syndrome, as this greatly affects their clinical management, and a personalized approach should be taken considering the individual's personal and family history, age, and other risk factors 1.
From the Research
Implications of BRCA1 Gene Mutation
The implications of a BRCA1 gene mutation are not directly addressed in the provided studies, as they primarily focus on the BARD1 gene and its relationship with breast and ovarian cancer. However, it is known that BRCA1 and BARD1 genes interact in DNA damage response and apoptosis initiation 2.
BARD1 Gene Mutations and Cancer Risk
Studies have shown that BARD1 mutations can increase the risk of breast and ovarian cancer. For example, a study found that three BARD1 mutations (P24S and R378S) can synergetically impair the DNA damage response and lead to tumors in vitro and in vivo 3. Another study identified 16 different BARD1 sequence variants, five of which were novel, and suggested that BARD1 mutations may be regarded as cancer risk alleles 2.
Specific BARD1 Mutations and Their Effects
Certain BARD1 mutations have been found to impair DNA damage repair, making cells more sensitive to chemotherapeutic drugs such as cisplatin and olaparib 4. Additionally, a study found that deletion mutation at rs28997575 site of BARD1 can increase the risk of breast cancer, while the mutation genotype of rs2229571 locus can reduce the risk of breast cancer 5.
Key Findings
- BARD1 mutations can increase the risk of breast and ovarian cancer 6, 2
- Certain BARD1 mutations can impair DNA damage repair and make cells more sensitive to chemotherapeutic drugs 4
- Specific BARD1 mutations, such as deletion mutation at rs28997575 site, can increase the risk of breast cancer, while others, such as mutation genotype of rs2229571 locus, can reduce the risk 5
- Family history is associated with BARD1 gene polymorphism and may be a risk factor for breast cancer 5