Investigation of Tumour Spectrum of Germline Mutations in Breast and Ovarian Cancer Genes.

NCT03246841 | Active Not Recruiting DMC

• 3 other identifiers: UC-0104/1605 - TUMOSPEC2016-A00338-43ONCO04
• Study Type: interventional
• Target: 7,274
• Locations: 1 country
• Sites: 2

Brief Summary

TUMOSPEC is a national family study designed to measure the relative and absolute risk of cancer for carriers of deleterious mutations to these "new" breast cancer (BC) susceptibility genes. Index cases will be enrolled consecutively from patients attending an appointment at one of the Unicancer centres, with no other inclusion criteria, and offered a BRCA1/2 analysis as part of their care plan. A panel of 24 TUMOSPEC genes, chosen in advance by a steering committee, will be tested as the same time as the BRCA1/2 genes, at one of the usual BRCA1/2 analysis laboratories belonging to the same network and participating in the study. If a mutation is found, the index cases will be asked to invite their first and second degree family members and their cousins to take part in the study, regardless of whether they have cancer. Saliva samples will be then taken and used for a targeted analysis of the familial abnormality. Each participant will also complete an epidemiological questionnaire in order to gather information about his/her medical history and any exposure to various risk factors. All medical and genotype data will be centralised at the Genetic Epidemiology Research Platform (PIGE, INSERM). The cumulative mutation frequency for all genes is estimated at 10%. Penetrance will be analysed using methods designed to minimise selection bias. The expression spectrum of the mutations will also be described. For genes where the number of mutated families is too low, the data may be contributed to international consortia. The main project will be preceded by a two-year feasibility study, using the same inclusion criteria and logistic circuits. It is this pilot study to which the current funding application relates.

Conditions

Hereditary Breast and Ovarian Cancer; Mutation

Keywords

Oncogeneticists; Mutations; Breast Cancer; Ovarian cancer

Outcome Measures

Primary Outcomes (1)

• Penetrance estimation of the mutations identified in the gene panel

  The primary outcome is to obtain unbiased penetrance estimates of the mutations identified in the gene panel (about 20 genes), which will be analysed by the molecular diagnostic laboratories at the same time as the BRCA1 and BRCA2 genes

  2 years

Secondary Outcomes (2)

• The results for the whole panel sequencing will be formatted to be used by all laboratories allowing the subsequent centralisation of the data.

  2 years

• Relative risk will be determined by the ratio of calculated cancer incidence in mutated and non-mutated families for this gene.

  2 years

Study Arms (1)

Analysis of the gene panel

OTHER

The laboratory will carry out the TUMOSPEC gene panel analysis at the same time as the BRCA1 and BRCA2 analysis and will return a negative (no mutation) or positive (presence of a mutation allowing enrolment of family members) result.

Other: Genetic testing

Interventions

Genetic testing OTHER

A panel of 24 genes, chosen in advance by a steering committee, will be tested as the same time as the BRCA1/2 genes, at one of the usual BRCA1/2 analysis laboratories belonging to the same network and participating in the study.

Analysis of the gene panel

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Index case eligibility:
• Any person with an indication for a BRCA1/BRCA2 gene analysis and who has been offered TUMOSPEC panel screening.
• Age ≥18 years.
• Family member eligibility:
• Family members will be eligible if the mutation identified in the Index Case is considered deleterious.
• Any family member to the first and second decree or a cousin of the Index Case. Family members from both sides of the family will be invited to take part.
• Age ≥18 years.

You may not qualify if:

• People deprived of their civil liberties or who are under judicial protection or guardianship.
• Patients unable to answer the questionnaire for social or psychological reasons.
• Children of the index cases, of any age.

Sponsors & Collaborators

• UNICANCER: lead
• Institut Curie: collaborator
• Gustave Roussy, Cancer Campus, Grand Paris: collaborator
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator

Study Sites (2)

Gustave Roussy

Paris, France

Location

Institut Curie - PIGE

Paris, France

Location

Related Publications (1)

• Lesueur F, Eon-Marchais S, Bonnet-Boissinot S, Beauvallet J, Dondon MG, Golmard L, Rouleau E, Garrec C, Martinez M, Toulas C, Nguyen TD, Brayotel F, Crivelli L, Maugard CM, Bubien V, Sevenet N, Gesta P, Chieze-Valero S, Nambot S, Goussot V, Mari V, Popovici C, Prieur F, Morin-Meschin ME, Tinat J, Lortholary A, Dreyfus H, Bidart M, Collonge-Rame MA, Mozelle-Nivoix M, Gladieff L, Giraud S, Boutry-Kryza N, Chiesa J, Denizeau P, Bignon YJ, Uhrhammer N, Cohen-Haguenauer O, Vilquin P, Mailliez A, Coupier I, Rey JM, Lacaze E, Bera O, Colas C, Coulet F, Delnatte C, Houdayer C, Lasset C, Lemonnier J, Longy M, Nogues C, Stoppa-Lyonnet D, Vaur D, Andrieu N, Caron O. TUMOSPEC: A Nation-Wide Study of Hereditary Breast and Ovarian Cancer Families with a Predicted Pathogenic Variant Identified through Multigene Panel Testing. Cancers (Basel). 2021 Jul 21;13(15):3659. doi: 10.3390/cancers13153659.

  PMID: 34359559 BACKGROUND

MeSH Terms

Conditions

Hereditary Breast and Ovarian Cancer Syndrome; Breast Neoplasms; Ovarian Neoplasms

Interventions

Genetic Testing

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Neoplastic Syndromes, Hereditary; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Study Officials

• Olivier CARON, MD

  Gustave Roussy, Villejuif, France

  PRINCIPAL INVESTIGATOR

• Andrieu Nadine, PhD

  Institut Curie, Paris, France

  PRINCIPAL INVESTIGATOR

• Severine Eon Marchais, PhD

  PIGE Institut Curie, Paris, France

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2017
• First Posted: August 11, 2017
• Study Start: September 21, 2017
• Primary Completion: September 30, 2025
• Study Completion: December 31, 2025
• Last Updated: December 12, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Unicancer will consider access to study data upon written detailed request sent to Unicancer, from 6 months until 5 years after publication of summary data.
• Access Criteria: The data shared will be limit to that required for independent mandated verification of the published results, the applicant will need authorization from Unicancer for personal access, and data will only be transferred after signing of a data access agreement.

Locations

FR (2)