TUMOSPEC: A Nation-Wide Study of Hereditary Breast and Ovarian Cancer Families with a Predicted Pathogenic Variant Identified through Multigene Panel Testing

Nom de la revue
Fabienne Lesueur, Séverine Eon-Marchais, Sarah Bonnet-Boissinot, Juana Beauvallet, Marie-Gabrielle Dondon, Lisa Golmard, Etienne Rouleau, Céline Garrec, Mathilde Martinez, Christine Toulas, Tan Dat Nguyen, Fanny Brayotel, Louise Crivelli, Christine M. Maugard, Virginie Bubien, Nicolas Sevenet, Paul Gesta, Stéphanie Chieze-Valero, Sophie Nambot, Vincent Goussot, Véronique Mari, Cornel Popovici, Fabienne Prieur, Marie-Emmanuelle Morin-Meschin, Julie Tinat, Alain Lortholary, Hélène Dreyfus, Marie Bidart, Marie-Agnès Collonge-Rame, Monique Mozelle-Nivoix, Laurence Gladieff, Sophie Giraud, Nadia Boutry-Kryza, Jean Chiesa, Philippe Denizeau, Yves-Jean Bignon, Nancy Uhrhammer, Odile Cohen-Haguenauer, Paul Vilquin, Audrey Mailliez, Isabelle Coupier, Jean-Marc Rey, Elodie Lacaze, Odile Béra, Chrystelle Colas, Florence Coulet, Capucine Delnatte, Claude Houdayer, Christine Lasset, Jérôme Lemonnier, Michel Longy, Catherine Noguès, Dominique Stoppa-Lyonnet, Dominique Vaur, Nadine Andrieu, Olivier Caron

Assessment of age-dependent cancer risk for carriers of a predicted pathogenic variant (PPV) is often hampered by biases in data collection, with a frequent under-representation of cancer-free PPV carriers. TUMOSPEC was designed to estimate the cumulative risk of cancer for carriers of a PPV in a gene that is usually tested in a hereditary breast and ovarian cancer context. Index cases are enrolled consecutively among patients who undergo genetic testing as part of their care plan in France. First- and second-degree relatives and cousins of PPV carriers are invited to participate whether they are affected by cancer or not, and genotyped for the familial PPV. Clinical, family and epidemiological data are collected, and all data including sequencing data are centralized at the coordinating centre. The three-year feasibility study included 4431 prospective index cases, with 19.1% of them carrying a PPV. When invited by the coordinating centre, 65.3% of the relatives of index cases (5.7 relatives per family, on average) accepted the invitation to participate. The study logistics were well adapted to clinical and laboratory constraints, and collaboration between partners (clinicians, biologists, coordinating centre and participants) was smooth. Hence, TUMOSPEC is being pursued, with the aim of optimizing clinical management guidelines specific to each gene.