Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT04206891 |
| Other study ID # |
IEO 0834/ |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
December 1, 2018 |
| Est. completion date |
December 30, 2023 |
Study information
| Verified date |
January 2023 |
| Source |
European Institute of Oncology |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial 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.
Description:
Invasive lobular breast carcinoma (ILBC) represents 5-15% of all invasive BCs. LBC presents
relevant differences in the transcriptomic profiles, metastatic pattern, and clinical
behaviour compared to infiltrating ductal BC.
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, updated clinical guidelines for CDH1 testing criteria have been published. For LBC,
CDH1 genetic screening has been suggested for families with diagnosed of both DGC and LBC
(one diagnosis before the age of 50) and patients with bilateral or familial LBC before the
age of 50.
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 investigators have revised all literature data about early-onset LBC and CDH1 germline
mutations, excluding pedigrees associated with DGCs. In detail, 482 cases of LBCs were
screened for CDH1 constitutional mutations. Family history for breast carcinoma was
documented in 40.7 % of the considered probands and 20.3 % presented a bilateral BC
manifestation. Mean age at onset was 46 years. Fourteen novels deleterious alterations (2.9
%) have been reported; 5 were missense (35.7 %), 3 mutations affected the splicing sites
(21.4 %), 3 deletions (21.4 %), 2 insertions (14.3 %) and 1 stop codon (7.2 %). These
mutations affect different CDH1 gene domains, spanning almost all 16 exons and introns 1-7-13
boundaries. Two missense mutations were defined as potentially pathogenic variants in vitro
and in silico analysis [Corso et al. Fam Cancer 2016]. Overall, about 3% of the screened
population with LBC have a mutation.
To date, no clear-cut genetic indicators for increased risk have been identified in patients
with lobular breast cancer (LBC).
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.
The investigators hypothesize that CDH1 is a susceptibility gene for LBC and that a novel and
rare syndrome (called as hereditary LBC), independent from the classic HDGC setting, should
be described, especially in subjects with early onset of LBC, before 45 years at diagnosis,
and in bilateral LBC manifestation.
