by Johanna Chelcun, MHS, PA-C
The role of the E-cadherin protein affected by CDH1 gene mutations is adhesion of adjacent cells in certain tissues of the body. In patients with a CDH1 gene mutation, the loss of E-cadherin is thought to lead to invasive tumors, most often in the lining of the stomach. However, a form of breast cancer called lobular breast cancer has also been associated with the CDH1 gene mutation and hereditary diffuse gastric cancer.
Lobular breast cancer caused by CDH1 mutations cause cancerous cells to be scattered throughout the breast tissue, making the cancer difficult to diagnose (much like hereditary diffuse gastric cancer). Additionally, the same type of cancer cells, called signet ring cells, are found in both lobular breast cancer and diffuse gastric cancers. This helps to solidify a relationship between the CDH1 gene mutation and an increased risk of both diffuse gastric cancer and lobular breast cancer. To date, lobular breast cancer is the only cancer besides gastric that is known to occur at increased rates in families affected by a CDH1 gene mutation.
Risk of developing lobular breast cancer
In females with a known CDH1 gene mutation, the risk for developing lobular breast cancer by age 80 has been estimated at anywhere between 39% and 54%, depending on the source. Scientific studies vary widely in risk determination due to the small number of affected patients.
Because lobular breast cancer is difficult to detect due to its diffuse pattern of growth, breast surveillance is of the utmost importance for females in HDGC families. It has been recommended that females affected by a CDH1 gene mutation practice monthly breast self-examination, have clinical breast examinations by a medical provider every six months, and begin yearly mammograms beginning by age 30 to 35. Additionally, the roles of breast MRI as well as ultrasound have been discussed due to the difficulty of cancer detection by mammogram. Medication therapy with hormones (tamoxifen or raloxifene) is also a consideration in the prevention and risk reduction of lobular breast cancer.
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