Epithelial ovarian cancer (EOC) is one of the most lethal gynecologic malignancies. Mutations in the BRCA1 and BRCA2 genes significantly increase the risk of developing this cancer. Understanding the implications of BRCA mutations on ovarian cancer can help optimize screening, prevention, and treatment strategies.
Understanding BRCA Mutations and Ovarian Cancer Risk
BRCA1 and BRCA2 are tumor suppressor genes responsible for DNA repair. Mutations in these genes impair DNA damage repair, leading to an increased risk of several cancers, including ovarian cancer.
- BRCA1 Mutation: 35–45% lifetime risk of ovarian cancer
- BRCA2 Mutation: 10–20% lifetime risk of ovarian cancer
- General Population Risk: ~1.3% lifetime risk
Women with BRCA mutations are also more likely to develop high-grade serous ovarian carcinoma (HGSOC), the most common subtype of EOC.
Symptoms of BRCA-Associated Epithelial Ovarian Cancer
EOC symptoms often appear in advanced stages, making early detection difficult. Common symptoms include:
- Persistent bloating or abdominal swelling
- Pelvic pain or pressure
- Early satiety or difficulty eating
- Frequent urination
- Unexplained weight loss
- Fatigue
Diagnosis of BRCA-Mutated Epithelial Ovarian Cancer
Diagnosis involves a combination of imaging, blood tests, and genetic analysis:
- Pelvic Ultrasound & CT/MRI: To detect tumors
- CA-125 Blood Test: Measures a protein often elevated in ovarian cancer
- Tissue Biopsy: Confirms cancer histology
- Genetic Testing: Determines BRCA mutation status, crucial for personalized treatment
Treatment Options for BRCA-Mutated Epithelial Ovarian Cancer
1. Surgical Management
Debulking surgery is the first-line treatment, aiming for complete tumor removal. BRCA-mutated cases often respond better to surgery and chemotherapy.
2. Platinum-Based Chemotherapy
BRCA-mutated ovarian cancers exhibit higher sensitivity to platinum agents such as carboplatin and cisplatin.
3. PARP Inhibitors (Targeted Therapy)
Poly (ADP-ribose) polymerase (PARP) inhibitors block DNA repair pathways, making them highly effective in BRCA-mutated ovarian cancer.
- Olaparib (Lynparza)
- Rucaparib (Rubraca)
- Niraparib (Zejula)
4. Hormonal & Immunotherapy Approaches
- Hormonal Therapy: Tamoxifen and aromatase inhibitors may be considered for certain cases.
- Checkpoint Inhibitors: Immunotherapy trials are ongoing to enhance response in BRCA-mutated cases.
5. Risk-Reducing Strategies
- Risk-Reducing Salpingo-Oophorectomy (RRSO): Preventive removal of ovaries and fallopian tubes reduces ovarian cancer risk by over 90% in BRCA carriers.
- Oral Contraceptives: Long-term use lowers ovarian cancer risk by 50%.
Prognosis and Survival Rates
BRCA-associated ovarian cancers often have better initial responses to chemotherapy compared to non-BRCA cases. However, long-term recurrence remains a concern. Studies suggest BRCA mutation carriers have a median survival of 6–10 years post-diagnosis, with variations based on treatment response.
