LobularCard Trial: Searching for Novel Germline Mutations in Lobular Breast Cancer Patients

BRCA1 Mutation Clinical Trial

— LobularCard  

Official title:

LobularCard Trial: Searching for Novel Germline Mutations in Lobular Breast Cancer Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05410951
• Other study ID #: IEO 1730
• Status: Recruiting
• Start date: May 16, 2022
• Est. completion date: May 16, 2027

Study information

• Verified date: September 2022
• Source: European Institute of Oncology
• Contact: Giovanni Corso, PhD
• Phone: +390294375161
• Email: giovanni.corso[@]ieo.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is a cross-sectional and retrospective study of a cohort of patients with invasive lobular breast cancer (LBC) or in situ lobular neoplasia (LIN3).

The main endpoint is the relative frequency of patients with a germline mutation using a recent panel including 113 genes from the "Illumina" protocol.

In case of identification of a novel pathogenetic germline mutations, a personalized follow-up will be offered to each patient (in case of genes at moderate-, low-penetrance), or prophylactic mastectomy (in case of genes at high-penetrance).

Breast screening in moderate-, low-penetrance mutated patients should be performed periodically using digital mammography, ultrasound and MRI, and will be routinely observed.

Patients will be scheduled for follow-up at six-month intervals for 5 years at our outpatient clinic, and yearly thereafter

Description:

Pathogenic or likely pathogenic variants (commonly referred to as mutations) in high-penetrance breast cancer (BC) susceptibility genes increase the risk of BC more than fourfold. Germline mutations in BRCA1 or BRCA2 (BRCA1/2) are found in 3% to 4% of all women with BC, including 10% to 20% of those with triple-negative breast cancer (TNBC) and 10% to 15% of Jewish women with BC.

Recent international guidelines consider only a small group of gene as high-penetrance risk:

BRCA1/2, CDH1, PTEN, and PALB2 [2], the remaining are classified as moderate-, low-penetrance risks.

There are no specific associations between these germline mutations and BC histotypes. In accord with recent genetic results reported in literature, lobular histotype seems associated with a specific germline pathway.

We hypothesize that other genes are associated with a susceptibility for lobular breast carcinoma (LBC) predisposition and that novel genetic factors should be described, especially in subjects with early onset of LBC.

In this context we selected a recent panel including 113 genes from the "Illumina" protocol.

The screening analysis will be performed by Next Generation Sequencing (NGS) technology using the TruSight Hereditary Cancer panel (Illumina) to analyze the entire coding regions of 113 genes selected genes and 125 SNPs, starting from 50 ng of gDNA extracted with MagCore HF16 Plus (Diatech Labline).

The proposed project is scheduled in three major tasks:

1) Data collection, including family history assessment and pedigree analysis for eligible subjects deserving genetic screening; 2) Genomic characterization of LBC in subjects with germline mutation; 3) Evaluation of disease-free survival and overall survival in subjects with germline mutation and establishment of a specific clinical follow-up for these patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 800
• Est. completion date: May 16, 2027
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 99 Years

Eligibility

Inclusion criteria:

1. All LBC observed retrospectively at the European Institute of Oncology, with a proved diagnosis of LBC (biopsy or operated)

2. Patients with blood available in biobank Exclusion criteria

• Patients with a previous cancer (except skin basal cell carcinoma)

• Patients with ductal or mixed BC

Related Conditions & MeSH terms

• BRCA1 Mutation
• BRCA2 Mutation
• Breast Neoplasms
• Carcinoma
• Carcinoma, Lobular
• Lobular Breast Carcinoma

Intervention

Diagnostic Test:
• Illumina panel
Determination of germline mutations using a recent panel including 113 genes from the "Illumina" protocol

Locations

Country	Name	City	State
Italy	European Institute of Oncology	Milan

Sponsors (1)

Lead Sponsor	Collaborator
European Institute of Oncology

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relative frequency of patients with a germline mutation	Frequency of germline mutation status in patients with in situ (LIN3) or invasive LBC or bilateral LBC or LBC with or without family history for breast cancer	1 month
Secondary	Correlation of clinic-pathological data between genes at high-penetrance versus other genes	correlation of clinic-pathological data between genes at high-penetrance (BRCA1/2, CDH1, PTEN, and PALB2) vs. other genes	1 month
Secondary	Prevalence of germline mutation status by clinical strata	Prevalence of germline mutation status by early onset LBC (age <45 years), bilateral LBC, LBC with family history for breast cancer	1 month
Secondary	Association with disease free survival and overall survival	prognostic role of mutation status: the association with disease free survival and overall survival	5 years
Secondary	Association of mutation status with molecular subtypes	association of mutation status with molecular subtype of primary tumor (Luminal A, Luminal B, Basal-like, HER2-enriched)	3 months