What are other Names for this Condition? (Also known as/Synonyms)

• Hereditary Lobular Breast Cancer

What is CDH1-Associated Breast Cancer? (Definition/Background Information)

• CDH1-Associated Breast Cancer is a cancer susceptibility syndrome. It is generally characterized by lobular carcinoma (cancer that starts in the cells) of the breast. The syndrome is caused by germline mutations in the CDH1 gene that is inherited in an autosomal dominant inheritance pattern
• Having a family history of CDH1-Associated Breast Cancer has been shown to increase the risk of developing the condition. The condition may occur alongside hereditary diffuse gastric cancer (HDGC) which is also caused by mutations in the CDH1 gene
• The main signs and symptoms include breast thickening/rippling, inverted nipples, and a change in appearance of the breast(s). CDH1-Associated Breast Cancer can be diagnosed with standard gene sequence testing
• A treatment of CDH1-Associated Breast Cancer is undertaken in case of cancer development. This may involve surgery and other modalities, such as radiation therapy and chemotherapy. The overall outcomes depends on the type and severity of the associated breast cancer

Who gets CDH1-Associated Breast Cancer? (Age and Sex Distribution)

• Female CDH1 mutation carriers have a 40% lifetime risk of developing CDH1-Associated Breast Cancer. The condition appears to be more common in females than males
• The frequency of a germline mutation in the CDH1 gene is very low in women with early-onset lobular breast carcinoma
• There does not appear to be any ethnic of geographic disparity in the occurrence of this genetic condition

What are the Risk Factors for CDH1-Associated Breast Cancer? (Predisposing Factors)

The following are risk factors associated with CDH1-Associated Breast Cancer:

• Having a personal history of breast cancer at a younger age without an identifiable mutation in the BRCA1/BRCA2 genes
• A family history of cancer, specifically breast or gastric cancers
• Exposure to certain carcinogens including tobacco smoke or radiation exposure
• Having being diagnosed with hereditary diffuse gastric cancer (HDGC)

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one's chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of CDH1-Associated Breast Cancer? (Etiology)

CDH1-Associated Breast Cancer is inherited in an autosomal dominant manner. The risk of passing the altered gene from the affected parent to one’s offspring is 50% for each pregnancy.

• CDH1 is a gene located on chromosome 16. The gene normally functions to provide instructions for the construction of a protein called E-cadherin
• This protein is generally found in the membrane surrounding the epithelial cells. Mutations in the CDH1 gene disrupt this protein creation pathway and may lead to the development of lobular breast cancer
• CDH1-Associated Breast Cancer generally begins in the milk-producing glands (lobules) in women

Autosomal dominant mode of inheritance: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of CDH1-Associated Breast Cancer?

The following are possible signs and symptoms associated with CDH1-Associated Breast Cancer:

• Thickening of part of breast
• New area of fullness in the breast
• Change in texture or appearance of the breast such as dimpling or thickening 
• Inverted nipple
• Bloody discharge from nipple
• Pain in breast

How is CDH1-Associated Breast Cancer Diagnosed?

The following tests and exams may be used in the diagnosis of CDH1-Associated Breast Cancer:

• Complete physical exam, including breast exam, and evaluation of family medical history
• Genetic testing
• Mammogram
• Blood tests, as suitable
• Breast ultrasound
• CT and MRI scan 
• Breast biopsy
• Bone scan

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the Possible Complications of CDH1-Associated Breast Cancer?

Individuals with CDH1-Associated Breast Cancer who develop cancer may experience the following possible complications:

• Depression
• Secondary cancers (gastric cancer specifically)
• Malignancy of the cancer - invasion and spread of cancer to other body regions
• Increased sensitivity to radiation and external carcinogens
• Side-effects from chemotherapy
• Lymphedema, or the swelling of an arm, can occur after surgery or radiation therapy.

How is CDH1-Associated Breast Cancer Treated?

The following measures may be taken to treat the breast cancer caused as a result of CDH1 mutation: 

• Surgical removal of the tumor, including mastectomy
• Radiation therapy
• Chemotherapy
• Hormone therapy
• Genetic counseling 

Regular observation and periodic checkups to monitor the condition is highly recommended.

How can CDH1-Associated Breast Cancer be Prevented?

It is not possible to completely prevent CDH1-Associated Breast Cancer because it is a hereditary condition.

• However, one can take certain preemptive measures to be on the lookout for the development of CDH1-Associated Breast Cancer including, self-breast examinations, annual MRIs, and screening mammograms
• In certain cases, mastectomy may be an option to prevent the development of tumors into the future
• In general, it is also important to maintain a healthy lifestyle and take measures to prevent unnecessary exposure to environmental carcinogens
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks before planning for a child

What is the Prognosis of CDH1-Associated Breast Cancer? (Outcomes/Resolutions)

The prognosis of individuals with CDH1-Associated Breast Cancer may vary from one to another. Currently, new and improved treatments are helping to increase the longevity of individuals with breast cancer. Nevertheless, cancer recurrence or spread/metastasize to other areas of the body even with proper treatment may take place.

In general, the following factors are used to determine each individual’s prognosis:

• Staging of the cancer
• Location and size of the tumor
• Type of breast cancer
• Hormone-receptor status of breast cancer
• Presence of tumor indicators such as HER2 proteins (growth-promoting proteins)
• Cell growth rate
• Likelihood of cancer returning
• Age of the individual
• Menopausal status

Additional and Relevant Useful Information for CDH1-Associated Breast Cancer:

It is estimated that 1 in 8 women will be diagnosed with Breast Cancer during their lifetime. This means that approximately 220,000 women (in the US) will be diagnosed with the disease and fatalities may be around 40,000.