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

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

Study Overview

• Status: Active, not recruiting
• Conditions: BRCA1 Mutation; BRCA2 Mutation; Lobular Breast Carcinoma; Lobular in Situ Breast Carcinoma
• Intervention / Treatment: Diagnostic test: Illumina panel

Detailed 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.

• Study Type: Observational
• Enrollment (Estimated): 800

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy
    • European Institute of Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with in situ (LIN3) or invasive LBC or bilateral LBC or LBC with or without family history for BC, with blood sample available in European Institute of Oncology biobank

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Association with disease free survival and overall survival	prognostic role of mutation status: the association with disease free survival and overall survival	5 years
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

Collaborators and Investigators

• Sponsor: European Institute of Oncology
• Investigators: Principal Investigator: Giovanni Corso, PhD, MD, European Institute of Oncology

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2022
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): May 16, 2026

Study Registration Dates

• First Submitted: June 6, 2022
• First Submitted That Met QC Criteria: June 6, 2022
• First Posted (Actual): June 8, 2022

Study Record Updates

• Last Update Posted (Estimated): December 4, 2025
• Last Update Submitted That Met QC Criteria: November 27, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Skin Diseases; Breast Diseases; Carcinoma; Neoplasms, Ductal, Lobular, and Medullary; Breast Neoplasms; Carcinoma in Situ; Skin and Connective Tissue Diseases; Breast Carcinoma In Situ; Carcinoma, Lobular
• Other Study ID Numbers: IEO 1730

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No