Genomic profiling is now recommended for initial evaluation of gynecologic cancers to identify molecular subtypes and hereditary syndromes.
Approximately 20 to 25% of ovarian cancers are associated with germline pathogenic variants in BRCA1/2 or other moderate penetration genes in the homologous recombination pathway such as ATM, BRIP1, RAD51C, RAD 51DM and PALB2.
In endometrial cancer, molecular classification (POLE-mutated, MSI-H/dMMR, p53-aberrant, NSMP) is used to complement histopathology and guide further testing for Lynch syndrome and other hereditary conditions.
Prognosis: Molecular subtypes are strongly associated with clinical outcomes. POLE-mutated endometrial cancers have excellent prognosis, while p53-aberrant tumors are more aggressive and require multimodal therapy.
5 to 10% of ovarian tumors harbor a somatic mutation of BRCA1/2 and overall 50% will exhibit homologous recombination deficiency.
In ovarian cancer, germline and somatic BRCA1/2 testing is recommended for all patients, as it identifies hereditary cancer risk and informs family counseling.
The addition of maintenance therapy in the form of poly adenosine phosphate ribose polymerase (PARP) inhibition is revenue has revolutionized upfront management of advanced ovarian cancers associated with germline pathogenic variants and somatic mutations in BRCA 1/2.
In ovarian cancer, homologous recombination deficiency (HRD) status predicts response to platinum-based chemotherapy and PARP inhibitors.
Genomic alterations such as MSI-H/dMMR also have prognostic and therapeutic implications in endometrial and cervical cancers.
Genomic findings increasingly guide targeted therapy: Actionable mutations (e.g., BRCA1/2, PIK3CA, ERBB2, NTRK fusions) enable use of PARP inhibitors, PI3K/AKT/mTOR inhibitors, immune checkpoint inhibitors, and other targeted agents.
Comprehensive genomic profiling identifies patients eligible for clinical trials and matched therapies, which is associated with improved survival in several studies.