Universal tumor DNA BRCA1/2 testing of ovarian cancer: prescreening PARPi treatment and genetic predisposition
Menée à partir d'échantillons tumoraux fixés au formaldéhyde et inclus en paraffine après prélèvement sur 315 patientes atteintes d'un cancer de l'ovaire récemment diagnostiqué, puis menée à partir d'entretiens téléphoniques avec 13 patientes et de questionnaires auprès de 18 gynécologues, cette étude multicentrique évalue la possibilité d'utiliser en routine un test universel recherchant des variants pathogènes au niveau des gènes BRCA1/2 pour identifier les patientes pouvant bénéficier d'un traitement par inhibiteurs de PARP
Background : Women with epithelial ovarian cancer (OC) have a higher chance to benefit from PARP inhibitor (PARPi) therapy if their tumor has a somatic or hereditary BRCA1/2 pathogenic variant. Current guidelines advise BRCA1/2 genetic predisposition testing for all OC patients, though this does not detect somatic variants. We assessed the feasibility of a workflow for universal tumor DNA BRCA1/2 testing of all newly diagnosed OC patients as prescreen for PARPi treatment and cancer predisposition testing.
Methods : Formalin fixed paraffin embedded (FFPE) tissue was obtained from OC patients in seven hospitals, immediately after diagnosis or primary surgery. DNA was extracted and universal tumor BRCA1/2 testing was then performed in a single site. Diagnostic yield, uptake, referral rates for genetic predisposition testing, and experiences of patients and gynecologists were evaluated.
Results : Tumor BRCA1/2 testing was performed for 315 (77.6%) of the 406 eligible OC samples, of which 305 (96.8%) were successful. In 51 of these patients pathogenic variants were detected (16.7%). Most patients (88.2%) went on to have a genetic predisposition test. BRCA1/2 pathogenic variants were shown to be hereditary in 56.8% and somatic in 43.2% patients. Participating gynecologists and patients were overwhelmingly positive about the workflow.
Conclusions : Universal tumor BRCA1/2 testing in all newly diagnosed OC patients is feasible, effective and appreciated by patients and gynecologists. Because many variants cannot be detected in DNA from blood, testing tumor DNA as the first step can double the identification rate of patients who stand to benefit most from PARP inhibitors.
Journal of the National Cancer Institute , article en libre accès, 2018