Ovarian cancer, ranked as the sixth most common cancer among women, holds the unfortunate distinction of being the leading cause of death stemming from female pelvic cancers. In India, its incidence ranges from 5 to 7 per 100,000 women, and there’s been a concerning upward trend in recent years. Ovarian cancer is notorious for its high mortality rate, primarily due to late-stage diagnoses. In its early stages, ovarian cancer often exhibits no specific symptoms, and by the time symptoms like vague abdominal pain, bloating, nausea, and vomiting appear, it’s typically in an advanced stage.
The lifetime risk of acquiring ovarian carcinoma in the general population is 1.3%. However, women with first- or second-degree relatives who have a history of breast, ovarian, endometrial, colon, or Lynch syndrome-related cancers are at a significantly higher risk, with probabilities ranging from 10% to 60%. Hereditary ovarian cancers tend to manifest at a younger age. Common genetic mutations associated with hereditary ovarian cancer include BRCA1, BRCA2, MLH1, MSH2, MSH6, PMS2 (Lynch syndrome), PALB2, and RAD51. Families with a history of multiple cancers should consider genetic counseling, and high-risk individuals should undergo BRCA1/BRCA2 gene testing or multi-gene testing through next-generation sequencing.
High-risk individuals should begin ovarian cancer screening 5-10 years earlier than the youngest age of diagnosis in their family. Screening typically involves transvaginal sonography and CA-125 measurement for those not opting for risk-reducing surgery, with screenings starting no later than age 35-40. Additionally, colonoscopies should be performed every 1-2 years from age 20-25 for those with a family history of Lynch syndrome, and annual mammography or MRI screenings should commence at age 30 or earlier for those with a family history of early-onset breast cancer.
For BRCA-positive and high-risk individuals who have completed their families, risk-reducing bilateral salpingo-oophorectomy (RRSO) is recommended. Prophylactic hysterectomy and salpingo-oophorectomy are advised for individuals with Lynch syndrome. The possibility of prophylactic risk-reducing bilateral mastectomy should be discussed with BRCA-positive individuals. For those who wish to delay or avoid RRSO, oral contraceptives (OCP) can be considered, as studies indicate they can reduce ovarian cancer risk by 45% to 60% in BRCA-positive individuals.
The field of cancer genetics has far-reaching implications for hereditary or familial cancer management, including prevention, screening, and treatment. PARP inhibitors, like Olaparib, are being used in the adjuvant setting and for maintenance in BRCA-positive ovarian cancers, leading to prolonged disease-free survival.
Two cases underscore the importance of early detection and genetic testing in ovarian cancer. A 45-year-old woman, whose mother and cousin had cancer, was BRCA-positive and found to have ovarian cancer at stage III. She is now disease-free after undergoing surgery, chemotherapy, and PARP inhibitor treatment. Another woman with a family history of ovarian cancer had regular screenings, leading to the early-stage detection of her own ovarian cancer, sparing her from adjuvant chemotherapy.
In conclusion:
All women with epithelial ovarian cancer should undergo genetic testing for better management and family risk assessment.
Adequate screening, particularly in high-risk individuals, can detect ovarian cancer at an early stage, reducing morbidity and mortality.
Enhanced surveillance and consideration of risk-reducing surgeries can effectively prevent ovarian cancer in high-risk women.