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Moving Molecular Testing to the Frontlines of Ovarian Cancer

Caroline Seymour
Published: Monday, Jun 10, 2019

Mihaela C. Cristea, MD

Mihaela C. Cristea, MD

High-grade serous and endometrioid carcinomas are predominantly driven by deficiencies in homologous recombination, whereas less common histologic subtypes are largely driven by genetic alterations. However, every patient, irrespective of histologic subtype, should have access to molecular testing to determine whether a germline or somatic mutation is present, said Mihaela C. Cristea, MD.

Bringing HRD companion diagnostics to market would aid clinicians in identifying the approximately 50% of patients with HRD high-grade serous cancers who are likely to benefit from PARP inhibitors, currently indicated as:
  • Monotherapy for the treatment of recurrent germline/somatic BRCA-positive ovarian cancer (olaparib [Lynparza] and rucaparib [Rubraca])
  • Maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer following a partial response (PR) or complete response (CR) to platinum therapy (niraparib [Zejula], olaparib, rucaparib)
  • Maintenance therapy in patients with germline/somatic BRCA-positive ovarian cancer who are in PR/CR to first-line platinum-based chemotherapy
However, clinical implications go beyond high-grade serous cancers, explained Cristea. For example, rare histologies, such as low-grade serous endometrioid and clear-cell carcinomas, are more likely to harbor mutations in the mitogen-activated protein kinase pathway, commonly reflected by mutations in KRAS, BRAF, and HER2.
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