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NCT Number: NCT05410951

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

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

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Lobular Breast Carcinoma Adenocarcinoma BRCA1 Mutation BRCA2 Mutation Breast Carcinoma In Situ Breast Diseases Breast Neoplasms Carcinoma Carcinoma in Situ Carcinoma, Lobular Lobular in Situ Breast Carcinoma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Ductal, Lobular, and Medullary Neoplasms, Glandular and Epithelial Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year–99 year

Sex eligibility

Female

Study type

Observational

Primary location

European Institute of Oncology

Milan, Italy

About this study

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:

  • 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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • All LBC observed retrospectively at the European Institute of Oncology, with a proved diagnosis of LBC (biopsy or operated)
  • Patients with blood available in biobank Exclusion criteria
  • Patients with a previous cancer (except skin basal cell carcinoma)
  • Patients with ductal or mixed BC

Treatment and study plan

Illumina panel

Diagnostic Test

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

Primary outcomes

  1. Relative frequency of patients with a germline mutation

    Time frame: 1 month

    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

Secondary outcomes

  1. Correlation of clinic-pathological data between genes at high-penetrance versus other genes

    Time frame: 1 month

    correlation of clinic-pathological data between genes at high-penetrance (BRCA1/2, CDH1, PTEN, and PALB2) vs. other genes

  2. Prevalence of germline mutation status by clinical strata

    Time frame: 1 month

    Prevalence of germline mutation status by early onset LBC (age <45 years), bilateral LBC, LBC with family history for breast cancer

  3. Association with disease free survival and overall survival

    Time frame: 5 years

    prognostic role of mutation status: the association with disease free survival and overall survival

  4. Association of mutation status with molecular subtypes

    Time frame: 3 months

    association of mutation status with molecular subtype of primary tumor (Luminal A, Luminal B, Basal-like, HER2-enriched)

Sponsors and collaborators

Lead sponsor

European Institute of Oncology

Other

Registry information

Acronym: LobularCard

Important dates

Study start
2022
Primary completion
2025
Study completion
2026
First posted
Jun 8, 2022
Registry last updated
Dec 4, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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