Case Report Lobular Breast Cancer in a CDH1 Splice Site Mutation Carrier: Case Report and Review of the Literature Terri P. McVeigh, 1 Joon K. Choi, 1 Nicola M. Miller, 1 Andrew J. Green, 2 Michael J. Kerin 1 Clinical Breast Cancer, Vol. 14, No. 2, e47-51 ª 2014 Elsevier Inc. All rights reserved. Keywords: Breast cancer risk, E-cadherin, Familial breast cancer, Genetic predisposition, Single gene mutation Case Report A 49-year-old woman presented with a 4-week history of ill-defined nodularity of her right breast. She underwent triple assessment in a dedicated symptomatic breast unit. Clinical exam- ination confirmed the presence of an indeterminate lesion, for which she underwent mammography, ultrasound, and image- directed biopsy. Histologic examination found an invasive lobular carcinoma. Subsequently, a wide local excision and sentinel lymph node biopsy were performed. Final histology found a 51-mm, grade 3, invasive lobular cancer with characteristic downregulation of epithelial cadherin (E-cadherin). The tumor was strongly positive for the estrogen receptor (ER) (score 7/8) and the progesterone receptor (PR) (score 6/8) but was negative for the ERBB2 (HER2/ neu) receptor. Final histologic TNM stage was pT3 N0 (0/6) M0. Her medical history was extremely interesting from a genetic viewpoint. In 2003, she underwent a prophylactic total gastrectomy, having been confirmed as bearing a splice site 49-2A>G mutation in the CDH1 gene (cadherin 1, type 1, E-cadherin [epithelial]). She also was a heterozygous carrier of the H63D mutation of HFE (hemochromatosis) and an obligate carrier of a mutation in the CFTR gene (cystic fibrosis transmembrane conductance regulator). Her daughter was affected by cystic fibrosis manifesting as signifi- cant hepatic and pancreatic disease, with associated portal hyper- tension, portal hypertensive gastropathy, and liver cirrhosis. She was found on genetic testing to be a compound heterozygote, with DF508 and R117H mutations of CFTR. The proband’s family history (Fig. 1) was notable for its high prevalence of gastric cancer. Two maternal aunts, an uncle, and a first cousin all succumbed to the disease. The patient’s mother developed breast cancer at the age of 74 years, which was also of lobular histology; it was 29 mm in maximal diameter, of the luminal A molecular subtype, and node negative. She later developed nodular basal cell carcinoma of the forehead at age 78. CDH1 Gene and E-Cadherin The CDH1 gene is a tumor suppressor located on chromosome 16q22.1. 1 Its function is to encode E-cadherin. E-cadherin is a member of the cadherin family of calcium-dependent adhesion molecules. The E-cadherin protein is found in epithelial cells and is expressed in the early stages of human development. This protein plays a key role in cellular adhesion and interacts with the actin cytoskeleton to regulate cell polarity, differentiation, growth, and migration. 2 E-cadherin binds to various catenins (eg, b-catenin, plakoglobin) to stabilize the cell adhesion complex within the Clinical Practice Points  CDH-1 gene mutations are known to predispose pa- tients to gastric and other cancers.  Mutations in CDH-1 gene also confer a high risk of lobular breast cancer, but this risk is of variable penetrance.  The role of prophylactic breast surgery in CDH-1 mutation carriers is therefore controversial.  Consideration should be given to risk-reducing sur- gery in female patients with CDH-1 mutations, in particular if there is an associated family history of breast as well as gastric cancers.  Minimal follow-up should include annual MRI-based imaging. 1 Discipline of Surgery, National University of Ireland Galway, Galway, Ireland 2 National Centre for Medical Genetics, Our Lady’s Hospital for Sick Children, Crumlin, Dublin, Ireland Submitted: Sep 9, 2013; Accepted: Oct 3, 2013; Epub: Oct 25, 2013 Address for correspondence: Terri P. McVeigh, Discipline of Surgery, Clinical Sciences Institute, National University of Ireland Galway, Galway, Ireland E-mail contact: terri.mcveigh@gmail.com 1526-8209/$ - see frontmatter ª 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clbc.2013.10.007 Clinical Breast Cancer April 2014 - e47