BRCA 1/2 Status as a Predictive Factor to Response to Platinum Based Chemotherapy in Cancer Ovary

Overview

The main objective of this prospective study is to assess the clinical outcomes of platinum based chemotherapy cases either cisplatin or carboplatin according to BRCA status in neoadjuvant and recurrent ovarian cancer.

Ovarian cancer was the third most common gynecological cancer globally in 2020. Ovarian carcinoma is the most common type of ovarian cancer, comprising over 90% of all ovarian cancer cases. It is the most lethal gynecologic malignancy in high-income countries. Approximately, 10-15% of epithelial ovarian cancer (EOC) patients carry germline mutation in BRCA1 or BRCA2. But,the majority of cases are sporadic. Increased body mass index (BMI) and hormone replacement therapy (HRT) have been proposed as major contributors along with smoking and occupational hazards e.g., asbestos exposure. Studies have reported that the prevalence of BRCA mutations varies among different epithelial ovarian ca ( EOC) subtypes, with prevalence of 20%-25% reported for the high-grade serous subtype , BRCA mutations were reported in \<10% of the endometrioid subtype and with very low frequency in clear cell subtype (6.3%). The absence of BRCA1/2 function is associated with a cumulative lifetime risk for developing epithelial ovarian cancer of 40% to 50% in patients who are BRCA1-mutation carriers and 20% to 25% in patients who are BRCA2-mutation carriers. Improved prognosis in terms of progression-free survival (PFS) and overall survival (OS), with higher partial response (PR) and complete response (CR) rates to platinum-containing regimens and longer treatment-free intervals, has been observed in retrospective studies of patients who are BRCA1/2-mutant carriers with ovarian cancer compared with patients who are non. However, despite a generally favorable response to first-line chemotherapy, the disease frequently recurs. Due to limited therapeutic options, sequential chemotherapy regimens are often used based on platinum sensitivity (determined by the platinum-free interval), residual toxicities, general condition/performance status, and co-morbidities, with suboptimal outcomes and cumulative toxicity. Treatment effectiveness decreases over time, with resistance to platinum drugs precluding diminished survival and quality of life. Germ-line BRCA mutations are associated with longer survival rates after ovarian cancer diagnosis and generally favorable response to platin-based therapy. No data available for recurrent cases to assess the response of platinum based chemotherapy in BRCA mutant or wild cases.

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Central Contacts