Study on Fertility Parameters in Women With Germline Variants in BRCA1 and BRCA2

NCT ID: NCT06710015

Last Updated: 2024-11-29

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Total Enrollment: 128 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-12-01
• Study Completion Date: 2026-06-01

Brief Summary

Pathogenic variants (PVs) in the BRCA1 and BRCA2 genes are associated with an increased risk of developing breast and ovarian cancers. According to current guidelines from the National Comprehensive Cancer Network, the risk of developing breast cancer exceeds 60% for both genes, while the risk for ovarian cancer ranges from 39% to 58% for the BRCA1 and from 13% to 29% for the BRCA2. The detection of a pathogenic variant in the BRCA1 or BRCA2 genes necessitates both the establishment of appropriate primary and secondary surveillance measures for carriers and the discussion of the familial implications of such findings.

The molecular basis initially suggesting a possible association between germline variants in BRCA1 and BRCA2 genes and diminished ovarian reserve lies in the cellular impact of impaired or defective repair of DNA double-strand breaks (DSBs) on oocytes. Notably, BRCA1 and BRCA2 genes play a key role in the ATM-related mechanism for DSB repair through the homologous recombination (HR) pathway.

Although preclinical evidence supports a potential correlation between defective DSB repair and normal follicle maturation processes, clinical studies on large cohorts of patients with pathogenic BRCA1 and BRCA2 variants yield inconsistent results. This discrepancy is likely attributable to the inherent challenges in recruiting a sufficiently homogeneous and statistically significant sample size.

The aim of the study is to evaluate reproductive capacity in women carrying pathogenic variants in the BRCA1/2 genes by assessing the number of pregnancies during the period from January 1, 2018, to December 31, 2023. Secondary objectives include evaluating menopausal characteristics and pregnancy outcomes.

Conditions

BRCA1 and/or BRCA2 Variant Carriers; Fertility; Reproductive Age; Menopause; Pregnancy Outcomes

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: OTHER

Study Groups

BRCA1 and BRCA2 carriers

Inclusion criteria:

• age > 18 years
• presence of a pathogenic variant in the BRCA genes
• signed informed consent for study participation

No interventions assigned to this group

Control cohort

• >18 y.o
• Relatives up to the third degree of kinship from cohort 1 who tested negative on predictive testing for the familial pathogenic variant in the BRCA genes, matched for age where possible.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• age > 18 years
• presence of a pathogenic variant in the BRCA genes

• Relatives up to the third degree of the first cohort who tested negative on predictive testing for the familial pathogenic variant in the BRCA genes, matched for age where possible.

Exclusion Criteria

• presence of a pathogenic variant in another gene (not BRCA)
• significant psychiatric or clinical impairment affecting the ability to consent to the study

Control cohort

• absence of a pathogenic variant in another gene (non-BRCA) found in a family member
• significant psychiatric or clinical impairment affecting the ability to consent to the study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

OTHER

Sponsor Role: lead

Responsible Party

Lucci Cordisco Emanuela

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Emanuela Lucci Cordisco

Role: PRINCIPAL_INVESTIGATOR

Fondazione Policlinico Universitario A. Gemelli, IRCCS

Locations

UOC Genetica Medica Fondazione Policlinico Universitario A.Gemelli IRCCS

Roma, RM, Italy

Countries

Italy

Central Contacts

Emanuela Lucci Cordisco, MD

Role: CONTACT

Phone: +39 0630156780

Email: emanuela.luccicordisco@policlinicogemelli.it

Other Identifiers

6591

Identifier Type: -

Identifier Source: org_study_id