Hereditary lobular breast cancer with an emphasis on E-cadherin genetic defect

J Med Genet. 2018 Jul;55(7):431-441. doi: 10.1136/jmedgenet-2018-105337. Epub 2018 Jun 21.


Recent studies have reported germline CDH1 mutations in cases of lobular breast cancer (LBC) not associated with the classical hereditary diffuse gastric cancer syndrome. A multidisciplinary workgroup discussed genetic susceptibility, pathophysiology and clinical management of hereditary LBC (HLBC). The team has established the clinical criteria for CDH1 screening and results' interpretation, and created consensus guidelines regarding genetic counselling, breast surveillance and imaging techniques, clinicopathological findings, psychological and decisional support, as well as prophylactic surgery and plastic reconstruction. Based on a review of current evidence for the identification of HLBC cases/families, CDH1 genetic testing is recommended in patients fulfilling the following criteria: (A) bilateral LBC with or without family history of LBC, with age at onset <50 years, and (B) unilateral LBC with family history of LBC, with age at onset <45 years. In CDH1 asymptomatic mutant carriers, breast surveillance with clinical examination, yearly mammography, contrast-enhanced breast MRI and breast ultrasonography (US) with 6-month interval between the US and the MRI should be implemented as a first approach. In selected cases with personal history, family history of LBC and CDH1 mutations, prophylactic mastectomy could be discussed with an integrative group of clinical experts. Psychodecisional support also plays a pivotal role in the management of individuals with or without CDH1 germline alterations. Ultimately, the definition of a specific protocol for CDH1 genetic screening and ongoing coordinated management of patients with HLBC is crucial for the effective surveillance and early detection of LBC.

Keywords: E-cadherin; hereditary cancer; lobular breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / surgery
  • Cadherins / genetics*
  • Carcinoma, Lobular / diagnosis
  • Carcinoma, Lobular / genetics*
  • Carcinoma, Lobular / pathology
  • Female
  • Genetic Counseling
  • Genetic Predisposition to Disease
  • Germ-Line Mutation / genetics*
  • Heterozygote
  • Humans
  • Mastectomy


  • Cadherins

Supplementary concepts

  • Breast Cancer, Familial