Highlights
- •All women with ovarian cancer should be offered germline testing for BRCA mutations and other cancer susceptibility genes
- •Patients with deleterious BRCA mutations should be offered frontline maintenance therapy with a PARP inhibitor
- •Assays for homologous recombination deficiency may guide treatment options in patients without a deleterious BRCA mutation
- •Tumor molecular profiling may identify targeted therapies for off-label use in patients with limited treatment options
Abstract
Advances in next generation sequencing have allowed for rapid and economical germline
and tumor genomic profiling. Targeted therapies based on molecular tumor profiling
are now integrated into treatment guidelines for many solid tumors. In epithelial
ovarian cancer, 50% of tumors possess damaging mutations in homologous recombination
repair genes (aka homologous recombination deficiency or HRD) which includes the BRCA genes. Deleterious BRCA mutations and HRD have recently emerged as predictive biomarkers for the use of PARP
inhibitors in ovarian cancer. Every patient with ovarian cancer must be referred for
genetic counseling and germline testing for BRCA mutations. Multigene panel genetic testing may be more informative and cost-effective
than limited testing of cancer susceptibility genes. Patients without a germline deleterious
BRCA mutation must be assessed for a somatic BRCA mutation. Assays for HRD may help guide treatment options in women who do not have
a BRCA mutation. Currently, all patients with a germline or somatic BRCA mutation should be offered upfront maintenance therapy with a PARP inhibitor. During
May 2020, options for maintenance therapy with a PARP inhibitor were expanded to patients
with HRD and HR-proficient tumors.
Keywords
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Article info
Publication history
Published online: October 11, 2020
Accepted:
September 27,
2020
Received:
April 8,
2020
Identification
Copyright
© 2020 Published by Elsevier Inc.
