title: Ovarian cancer patients at high risk of BRCA mutation: the constitutional genetic characterization does not change prognosis.
abstract: Ovarian neoplasms secondary to germline BRCA mutations had been described to have a more favourable survival. There is only few data concerning the prognosis of non mutated patients presenting clinical features evocative of BRCA alterations. We retrospectively collected data from patients treated in our institution for an invasive ovarian carcinoma between 1995 and 2011. Patients considered at high risk of BRCA mutation were tested for BRCA1/2 germline mutations. We described clinical, pathological and therapeutic features and compared prognosis of BRCA mutation carriers and non-mutated patients. Out of 617 ovarian cancer patients, we identified 104 patients who were considered at high risk of mutation. The 33 mutated patients were more likely to present a personal (33 vs. 10 %, p = 0.003) or a family (42 vs. 24 %, p = 0.06) history of breast/ovarian cancers. BRCA1/2 mutation carriers and wild type patients displayed similar prognosis: median progression-free survival (PFS) of 20.9 versus 37.7 months (p = 0.21); median overall survival (OS) of 151.2 versus 122.5 months (p = 0.52). Personal history of breast cancer increased both PFS [HR = 0.45 (95CI 0.25-0.81)] and OS [HR = 0.35 (95CI 0.16-0.75)]. In multivariate analysis, this parameter was an independent prognostic feature, whereas the identification of a BRCA1/2 mutation was not. In our cohort, all patients at high risk of BRCA mutation share a similar prognosis, whatever is their germline mutation status. Prognosis seems to be more influenced by clinical history than by germline mutations identification. If it is confirmed in larger and independent series, this result suggests that the hypothesis of other BRCA pathway alterations (BRCAness phenotype) deserves to be deeply explored.
authors.affiliation: Department of Medical Oncology, Institut Paoli-Calmettes, 232 Boulevard Sainte-Marguerite, 13273, Marseille Cedex 09, France. sabatierr@ipc.unicancer.fr.|Centre de Recherche en Cancérologie de Marseille, INSERM U1068, CNRS U7258, Marseille, France. sabatierr@ipc.unicancer.fr.|Aix-Marseille University, Marseille, France. sabatierr@ipc.unicancer.fr.
authors.forename: Renaud
authors.initials: R
authors.lastname: Sabatier
authors.affiliation: Department of Medical Oncology, Institut Paoli-Calmettes, 232 Boulevard Sainte-Marguerite, 13273, Marseille Cedex 09, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Lavit
authors.affiliation: Cancer Control Department, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Jessica
authors.initials: J
authors.lastname: Moretta
authors.affiliation: Centre de Recherche en Cancérologie de Marseille, INSERM U1068, CNRS U7258, Marseille, France.|Department of Surgical Oncology, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Lambaudie
authors.affiliation: Department of Cancer Biology, Laboratory of Molecular Oncogenetics, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Noguchi
authors.affiliation: Cancer Control Department, Institut Paoli-Calmettes, Marseille, France.
authors.forename: François
authors.initials: F
authors.lastname: Eisinger
authors.affiliation: Department of Surgical Oncology, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Cherau
authors.affiliation: Department of Medical Oncology, Institut Paoli-Calmettes, 232 Boulevard Sainte-Marguerite, 13273, Marseille Cedex 09, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Provansal
authors.affiliation: Cancer Control Department, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Doriane
authors.initials: D
authors.lastname: Livon
authors.affiliation: Cancer Control Department, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Rabayrol
authors.affiliation: Department of Cancer Biology, Laboratory of Molecular Oncogenetics, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Cornel
authors.initials: C
authors.lastname: Popovici
authors.affiliation: Centre de Recherche en Cancérologie de Marseille, INSERM U1068, CNRS U7258, Marseille, France.|Aix-Marseille University, Marseille, France.|Department of Cancer Biology, Laboratory of Biopathology, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Charaffe-Jauffret
authors.affiliation: Aix-Marseille University, Marseille, France.|Department of Cancer Biology, Laboratory of Molecular Oncogenetics, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Hagay
authors.initials: H
authors.lastname: Sobol
authors.affiliation: Department of Medical Oncology, Institut Paoli-Calmettes, 232 Boulevard Sainte-Marguerite, 13273, Marseille Cedex 09, France.|Centre de Recherche en Cancérologie de Marseille, INSERM U1068, CNRS U7258, Marseille, France.|Aix-Marseille University, Marseille, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Viens
mesh_terms: D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D011379:Prognosis
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human
keywords: BRCA; Mutation; Ovarian cancer; Prognosis
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