511PD - Germline mutations in CDH1 and the hereditary diffuse gastric and lobular breast cancer syndrome

Date 01 October 2012
Event ESMO Congress 2012
Session Public health and familial cancer
Topics Breast Cancer
Familial Cancer
Presenter Patrick Benusiglio
Authors P.R. Benusiglio1, D. Malka2, A. De Pauw3, B. Buecher3, E. Rouleau4, C. Colas5, S. Grandjouan6, M. Blayau7, S. Delaloge8, O. Caron9
  • 1Clinical Genetics, Dept Of Medical Oncology, Institut Gustave Roussy, 94805 - Villejuif/FR
  • 2Oncology, Institut Gustave Roussy, 94805 - Villejuif/FR
  • 3Cancer Genetics, Institut Curie, 75248 - Paris/FR
  • 4Cancer Genetics, Centre Rene Huguenin, 92210 - Saint-Cloud/FR
  • 5Cancer Genetics, La Pitie Salpetriere, 75013 - Paris/FR
  • 6Gastroenterology, Hopital Cochin, 75014 - Paris/FR
  • 7Molecular Genetics, CHU de Rennes - Hôpital Pontchaillou, 35033 - Rennes/FR
  • 8Breast Cancer Unit, Department Of Medical Oncology, Institut Gustave Roussy, 94805 - Villejuif/FR
  • 9Clinical Cancer Genetics, Department Of Medical Oncology, Institut Gustave Roussy, 94805 - Villejuif/FR

Abstract

Background

Germline mutations in the E-cadherin gene (CDH1) are found in up to 48% of families with hereditary diffuse gastric cancer (HDGC), a syndrome characterized by multiple cases of DGC in a family. In 2010, experts updated CDH1 testing criteria and included individuals and families with diagnoses of both DGC and lobular breast cancer (LBC), as an excess of LBC had been observed in HDGC families. We describe the characteristics associated with CDH1 mutations in a group of French patients and show that individuals or families with multiple LBC but no DGC should be offered genetic testing.

Methods

We studied all index cases in which a CDH1 mutation had been identified between 2006 and 2011 in the Paris region.

Results

We found 17 index cases with a CDH1 mutation, ten males and seven females, age was 17–63. Eight had familial DGC, four had sporadic DGC at a young age, one was a healthy male with two relatives with DGC, and one was a female with LBC and two siblings with DGC. Additionally, three females (18%) with no personal or family history of DGC had suffered from bilateral LBC under age 50. Only one was tested at diagnosis. She was offered prophylactic gastrectomy, and foci of DGC were seen on the surgical specimen. She is now doing well. The two others, who had initial negative BRCA1/2 screening, were only tested for CDH1 mutations years later after they had developed symptomatic DGC.

Discussion

Three of our cases were females with bilateral LBC but no personal or family history of DGC. Two of them were only tested for CDH1 mutations once they had developed symptomatic DGC. Prophylactic gastrectomy is now systematically offered to mutation carriers, and these two cases would have been spared highly-lethal, symptomatic DGC, had they benefited from preventive surgery. The 2010 CDH1 testing criteria should be expanded and include cases or families with multiple LBC but no DGC. More precisely, any patient or family with multiple LBC under age 50 should be tested for CDH1 mutations, as carriers are offered life-saving surgery and adapted breast surveillance. Finally, we propose for consideration the name “hereditary diffuse gastric and lobular breast cancer” to define the cancer susceptibility syndrome associated with mutations in CDH1.

Disclosure

All authors have declared no conflicts of interest.