CDH1 Germline Mutations in Lobular Breast Cancer

NCT04206891 | Completed

• 1 other identifier: IEO 0834/
• Study Type: observational
• Target: 421
• Locations: 1 country
• Sites: 1

Brief Summary

Invasive lobular breast carcinoma (ILBC) represents 5-15% of all invasive BCs. The CDH1 gene (OMIM no. 192090), located on the chromosome 16q22.1, encodes for the E-cadherin protein, a key regulator of cell adhesion. Loss of E-cadherin expression is frequently detected in LBC CDH1 germline loss-of-function mutations are associated with the autosomal dominant cancer-predisposition syndrome, hereditary diffuse gastric cancer (HDGC; OMIM no. 137215). The cumulative risk of LBC for women with a CDH1 mutation is estimated to be 42% (95% CI 23% to 68%) by 80 years, when it is a component of HDGC syndrome. Recently, some authors described CDH1 germline mutations in women with in situ or ILBC with early onset (\<45 or \<50) and bilateral in situ or ILBC with no family history of HDGC. These results are opening a new scenario, suggesting that CDH1 could be a susceptibility gene for LBC in women without a family history of DGC. The first aim of this study is to investigate prevalence of CDH1 in this specific population of women with early onset (\<45 or \<50) in situ or ILBC, bilateral LBC or LBC with no family history of HDGC.

Conditions

Lobular Breast Carcinoma; CDH1 Gene Inactivation

Outcome Measures

Primary Outcomes (1)

• Relative frequency of patients with a mutation in CDH1 germline

  Number of patients with mutation in CDH1 germline per each group identified

  6 months

Secondary Outcomes (2)

• Frequency of patients with a mutation in CDH1 germline by disease status

  6 months

• Frequency of patients with a mutation in CDH1 germline by clinical strata

  6 months

Study Arms (5)

Group 1

Bilateral lobular invasive breast cancer

Group 2

Invasive lobular breast cancer with age at onset \<= 45 years

Group 3

Invasive lobular breast cancer with family history for breast cancer

Group 4

In situ lobular breast cancer with age at onset \<= 45 years

Group 5

In situ lobular breast cancer with family history for breast cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

From 1997 to 2016 we collected data from a total of 1544 patients with invasive LBC and 230 with in situ histotype. For CDH1 genetic screening, an additional population will be considered prospectively between the range 2017-2018 Among them we will have to identified patients with a BRCA1/2 pathogenetic mutation.

You may qualify if:

• Bilateral lobular breast cancer or Lobular breast cancer with age at onset \<= 45 years or Lobular breast cancer with family history for breast cancer
• Patients with blood available in IEO biobank

You may not qualify if:

• Patients with a previous cancer (except for colon cancer, stomach cancer and lobular breast cancer).
• Patients with germline BRCA1/2 patogenetic mutation will be excluded

Sponsors & Collaborators

• European Institute of Oncology: lead

Study Sites (1)

European Institute of Oncology

Milan, Italy

Location

MeSH Terms

Conditions

Carcinoma, Lobular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Ductal, Lobular, and Medullary; Breast Neoplasms; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Giovanni Corso, MD

  European Institute of Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2019
• First Posted: December 20, 2019
• Study Start: December 1, 2018
• Primary Completion: December 31, 2021
• Study Completion: November 26, 2025
• Last Updated: December 4, 2025

Record last verified: 2025-11

Locations

IT (1)