HDGC and the Increased Risk of Lobular Breast Cancer

by Johanna Chelcun, MHS, PA-C

Scientific Background

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.

Screening options

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. 


  • 1.) Blair V, Martin I, Shaw D, Winship I, Kerr D, et al. Hereditary Diffuse Gastric Cancer: Diagnosis and Management. Clinical gastroenterology and hepatology. 2006;4:262-275.
  • 2.) Guilford P, Blair V, More H, Humar B. A short guide to hereditary diffuse gastric cancer. Hereditary Cancer in Clinical Practice. 2007;5(4):183-194.
  • 3.) Schrader KA, Masciari S, Boyd N, Wiyrick S, Kaurah P, et al. Hereditary diffuse gastric cancer: association with lobular breast cancer. Familial Cancer. 2008;7:73-82.

6 Responses to HDGC and the Increased Risk of Lobular Breast Cancer

  1. hope2c83 says:

    I am finding it harder and harder to deal with ever new diagnosis and complication that has happed to my family since the death of my daughter 2 1/2 years ago. After 7 gastrectomies now there has been an aditional surgery, feeding tube and now lobular breast cancer. I was doing well when it was just have your stomach out and all will be good. I don’t know about all of you but the Dr’s have treated each step of this nightmare as “no problem you will all be fine” I do count my blessings that we are stomach cancer free and I personally am doing well (Just tired) I just hate to see the hardships of the people I care about. I get comfort to know from this sight that we are not alone. It does feel better to have some place to complain. Thanks!!

  2. Christine Lyons says:

    I was diagnosed with gastric cancer in 1993, 5 years after my brother passed away at age 36 of the disease. The doctors felt it was a “coincidence” After a partial gastrectomy, chemo and radiation I was shocked when 5 1/2 years later my endoscopic biopsy screening was positive for a new primary site. I was determined to find out more than my doctors and genetic counselors and they agreed to send out my blood for analysis. In 2007 6 months after my mom passed away with colon cancer,(indicating a similar type of tumor) I found out I did indeed have a CDH1 mutation. I did begin Tamoxifen, was switched to Evista, but then opted for a bilateral prophylactic mastectomy with reconstruction late in 2008. I never looked back and actually had diffuse atypical lobular hyperplasia in both breasts so my surgeon felt I dodged a bullet.
    Knowledge is power…So glad to see this site up and running!!!!!

  3. Lois Allard says:

    2 of my 3 adult children have the CDH1 gene. One has had the surgery.

    • Cindy says:

      Hi Lois,
      I apologize for not responding to your message much earlier! How are your children doing at this time? I also have two adult children who are positive for the CHD1 mutation, and one has had the surgery. After a challenging first few months, he is doing quite well at this point, 18 months later. Please send us an update when you can.
      All the best to all of you,
      Cindy Chelcun in Wisconsin

      • Andrea says:

        Hi Cindy, My family has just received genetic results that confirm the CHD1 mutation in my family. My mother passed away from complications with this cancer 8 years ago. Now her brother (my uncle) and my first cousin are battling it. My uncle had most of his stomach removed and has been fine for about 3-4 years, but my cousin (just 36 yrs old) has had a much worse time. It started in his stomach but has now metastasized to other parts of his intestines. He is severely malnourished and depends on feeding tubes and a colostomy bag.
        The rest of the family now has to decide if they want to get tested and if they will opt to have their stomachs removed if they are positive. I watched my mother go through years of constant surgeries and procedures that exhausted her literally until she could no longer fight.
        Being a daughter of a carrier, it is very scary to face the possibility. I realize it is in my best interest to get tested. We are all angry and scared.

        • Cindy says:

          Andrea, I can’t believe it has taken me this long to catch up with comments so I can respond. My apologies!
          My daughter had preventive surgery in December of last year, and joins her brother in being cured of gastric cancer caused by a CDH1 mutation. Both had tumors discovered in their post-surgery pathology, AND both are healthy and doing well now. They were each age 26 at the times of their surgeries.

          I hope you can tell me how you are, and how the others in your family are doing. I can certainly understand the feelings you describe in your comment.

          Take care, and I hope to hear from you here on NSFC, or you can start a discussion in the discussion forum and I’ll respond there!

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