Understanding How CDH1 Germline Mutations Affect Hereditary Lobular Breast Cancer
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 421
- 试验地点
- 1
- 主要终点
- Relative frequency of patients with a mutation in CDH1 germline
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
结局指标
主要结局
Relative frequency of patients with a mutation in CDH1 germline
时间窗: 6 months
Number of patients with mutation in CDH1 germline per each group identified
次要结局
- Frequency of patients with a mutation in CDH1 germline by clinical strata(6 months)
- Frequency of patients with a mutation in CDH1 germline by disease status(6 months)