Breast Cancer Events Associated with Germline Mutations of the CDH1 Gene (Hereditary Diffuse Gastric Cancer).

Abstract

Abstract Breast cancer events associated with germline mutations of the CDH1 gene (Hereditary Diffuse Gastric Cancer).Background: Mutations of the CDH1 (e-cadherin) gene are known to cause an autosomal dominant familial cancer syndrome, commonly referred to as hereditary diffuse gastric cancer. The lifetime risk of gastric cancer may be up to 80 percent. An associated risk of lobular breast cancer has been identified, but less well studied. Lifetime risk of breast cancer in affected women may be up to 50 percent.Method: We identified 17 women in our centre with known CDH1 mutations that have been offered genetic counseling for breast cancer risk. Counseling included discussion of prophylactic surgery, and breast screening via MRI/mammogram. We performed a chart review to identify breast cancer screening, prophylaxis, and treatment events in these patients.Results: 16 patients had adequate chart data to study. Of these, one patient had a breast cancer (T3N0M0) prior to mutation identification. 13 of 15 remaining patients entered into a high-risk breast-screening program with annual MRI and mammogram. Two breast cancers were identified in the first two years of patient screening; both were T1N0M0. Both women opted for bilateral mastectomy. No patient opted for prophylactic breast surgery prior to cancer detection, although several were in the process of prophylactic gastrectomy.Conclusion: To our knowledge, this is the first in-depth description of breast cancer events in patients with inherited CDH1 mutations. A majority of patients have opted for a breast-screening program, with successful early detection in two patients. Patients to date have not chosen primary prophylactic breast surgery, but two have chosen bilateral mastectomy upon detection of a malignancy. Further epidemiological studies are required to fully understand the breast cancer pattern and natural history that occurs in this genetic syndrome. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 904.