More About CDH1

The E-Cadherin gene or CDH1 is a tumor suppressor protein that maintains tissue integrity as it mediates cell-cell adhesion. It helps to regulate cells so that they don’t grow out of control or grow too rapidly.  For those who care, the CDH1 gene is located on chromosome 16q22.1 and it contains 2.6 kb of coding sequences with 16 exons.

In 1998, Dr. Parry Guilford first linked inherited mutations in the CDH1 gene with familial gastric cancer in three Maori families in New Zealand.  Many subsequent studies have been done and published papers can be found online.  Depending on your biological and medical knowledge, some are easier to read than others.  Because this is such a rare mutation, many of the studies have very small sample sizes and with each new study, the results change, sometimes considerably.

My gene mutation is c.2287G>T.  It is a nonsense truncation in Exon 14.  My results, dated May 22, 2015, indicate a 80% cumulative risk of diffuse gastric cancer by age 80 for both men and women, as well as a 39%-52% risk of lobular breast cancer for women.  There also may be an increase risk for colon cancer, but no percentage was listed in my test results.  In updated clinical guidelines, found in several articles online published February-May 2015, the cumulative risk for diffuse gastric cancer by age 80 is listed as 70% for men and 56% for women and the risk of lobular breast cancer is listed as 42%.  According to those guidelines, there is currently no evidence that the risk of other cancers is significantly increased in individuals with a CDH1 mutation.

Whether the risk is 80% or 56%, or something in between, the risk is high when you are talking about your life.  The recommendation of all the studies is that individuals who tested positive for a CDH1 mutation should consider prophylactic gastretomy regardless of other screening.  However, if the individual chooses not to have the gastrectomy or delays the gastrectomy, annual upper endoscopy is recommended with a minimum of 30 random biopsies.  However, the literature goes on to say that because of the very focal nature of these endoscopically invisible lesions, it is quite possible that they will not be detected by random biopsies.  So have the endoscopy, but more than likely, it won't find anything.

In almost 100% of the cases where a prophylactic total gastrectomy has been performed because of a CDH1 mutation, signet-ring cell carcinoma has been found in the pathology after the surgery, meaning that the patients are considered to have Stage 1 cancer.  However, because it is early stage and contained within the stomach, the surgery is curative and no further treatments are needed.

Telling the World

This is what I posted on Facebook this morning:


Two weeks from today I embark on the scariest journey of my life. When I was diagnosed with breast cancer in April 2015, I had genetic testing done. I tested positive for a very rare gene mutation, CDH1. While it is affiliated with breast cancer, it has an extremely high correlation with Hereditary Diffuse Gastric Cancer, cancer that forms in the lining of your stomach and is undetectable until stage 4 or 5 and it is too late. The only recommended course of treatment is to have a Prophylactic Total Gastrectomy, ie have your stomach removed as a preventive measure. After much research and agonizing, I have decided to have this surgery completed at MD Anderson in Houston on February 21. I appreciate your prayers for a smooth surgery, uneventful and swift recovery and for a lifetime of learning to live a normal life without a stomach, it can and has been done.

Making A Decision

It was November 12, 2016 when I shared this with family:

I have made what I believe is the hardest decision I have ever made in my life.  On February 21, I am going to have a prophylactic total gastrectomy, ie. I'm going to have my stomach removed.  As much as I don't want to do it, all evidence indicates that it is better than the alternative.  I think what really made me decide to do it was not so much the not wanting to die from stomach cancer (which I don't want to do), but more the not wanting to live the rest of my life in fear.  If I don't have the surgery then every time I don't feel quite right, I would be wondering "is this the cancer, is this the cancer".  I don't want to live my life like that.  And I have always taken doctors' advice about surgeries or procedures to have or whatever, so why was I questioning it this time and thinking I somehow knew better than the doctors.  This will be life changing, no doubt about it, but I have read several blogs online and talked to one person on the phone who is 4 years post surgery and there are plenty of people that have had the surgery for this exact reason and are living a "normal" life.

The surgery is on a Tuesday, but all of the pre-op appointments (surgeon, anesthesiologist, cardiac, x-ray, lab) are the Thursday before, so we will actually be headed down on Wednesday, February 15.  We are going January 5 to have another endoscopy done as it will be almost a year since the one we had down there last April and the surgeon wants a more recent one than that.  If we had it done at the same time in February, it would have to be the Tuesday before so they would have time to get pathology back and I just couldn't see being down there for a whole week before the surgery.  Also, Keith's vacation resets January 16, so by doing it in early January, those two days can be on this year's vacation time instead of next year's.

For more details about the actual surgery, I recommend this blog by two sisters who both had the surgery done in April by the same surgeon I will be using at MD Anderson.

Searching for Answers

My oldest daughter, Jesi, also tested positive for the CDH1 gene mutation. She had genetic testing done as soon as I was diagnosed with breast cancer because she actually had risk on both sides of the family.  She had her blood drawn the day before mine.  Hers was sent to a lab that was supposed to take two weeks longer than mine, but she actually got her results back a week before I got mine. However, she didn't tell me until I had my results as she was hoping it would be from her late dad's side of the family and I wouldn't have to worry about it.

 After spending several months researching ourselves and talking with genetic counselors, medical oncologist and gastric surgeon in Kansas City and not talking with anyone that had ever seen a patient with a CDH1 genetic mutation, we decided to go someplace where we could talk with people that have actually dealt with this gene mutation.  Through a friend of a friend type referral (not from any of our doctors), we connected with Dr. Paul Mansfield at MD Anderson in Houston and Jesi and I both met with him January 7, 2016.  We also met with a genetic counselor at MD Anderson. Both Dr. Mansfield and the genetic counselor have several patients with this gene mutation.  In some ways, we didn't learn anything new, but it was still helpful to hear it from someone who has seen it before.  

I had tried to convince myself that our family didn't fit the "typical" family with the mutation and HDGC (Hereditary Diffused Gastric Cancer) because we didn't have as many incidences of gastric cancer as most families; the genetic counselor said that actually we are a typical HDGC family.  They are finding more CDH1 mutations since it is now in the breast panel gene testing, but it is still a rare genetic mutation.  Because of the rarity and the small sample sizes, it is hard to determine the actual risk of gastric cancer, but they still believe it to be somewhere between 50-80%.

We heard the same answer that we had heard before, but it was helpful to hear it from someone with experience.  The only preventative measure is to have a prophylactic total gastrectomy.  The only recommended screening if you choose not to have a gastrectomy or before you do, is annual endoscopies with random biopsies.  Because the cancer develops in the stomach lining, it rarely shows up on an endoscopy, but that is the only screening available.  Jesi and I both had endoscopies done the previous summer because of the mutation, but rather than the 30 recommended biopsies, I had 3 and I think Jesi had 5.  Thus, the problem with seeing a doctor with no experience with the gene mutation.

The gastric surgeon we saw in Kansas City assured us that even though he hadn't done gastrectomies for CDH1, he has done plenty of them and "removing a stomach is removing a stomach."  What we learned at MD Anderson, is no, there is a difference in how you need to do the surgery so that you make sure you get every stomach cell, etc.

What I decided in January was that as much as it scared me to have the surgery, it also scared me not to.  At that time, I was leaning toward having the surgery, but waiting a year to do so.  I wanted the time to get myself emotionally ready, physically ready, ready at work, not miss any events around two weddings in 2016 (my youngest daughter and my nephew), etc.  I did of course run a risk by waiting, but I felt like I would be much more at peace with the decision in a year, so was willing to take what I thought/hoped was a small risk in waiting.  I decided in January, that if I did the surgery, I would definitely do it at MD Anderson rather than KC.  I learned that it would be approx 5 days in the hospital and then they want you to stay in town for another week in case of complications.  I felt that as much as I would rather be near my family and friends during that period, if I was gong to do this, I wanted the best and that was in Houston.  There would still be plenty of recovery time at home as the anticipation was to be off work 2-3 months.  Thus, part of the reason of wanting time to prepare.

My word to family in January 2016: "I don't like it, but that's where I am."

How it All Started

It was April 9, 2015 when I heard those dreaded words "you have breast cancer".  The cancer was found through routine mammogram and was in the very early stage so prognosis was very good.  The plan was to have a lumpectomy and then intense radiation called brachytherapy.  Since I had a family history of breast cancer, I decided to have genetic testing done first because of statistics like 80% of people with the BRAC1 gene will develop breast cancer again.

On Friday, May 22, two weeks after I was supposed to receive the results, just before leaving the office to come home for our Memorial Day weekend plans, I got a call from the genetic counselor.  She had the test results.  I tested positive for a very rare gene mutation, CDH1.

I learned from the genetic counselors and from doing my own research online, this gene mutation has a 39-52% (I've seen as high as 60%) risk for lobular breast cancer.  Interestingly enough, what I had was ductal breast cancer, so what I had may or may not actually have been caused by this gene, but the risk is still there of future breast cancers.  The scarier part is the 80% risk of Hereditary Diffuse Gastric Cancer (ie stomach cancer) by the age of 80.  What makes HDGC even scarier is that it develops in the lining of the stomach  and is undetectable by any early screening methods.  The only recommended course of treatment is to have a prophylactic total gastrectomy (removal of the stomach as a preventative measure).

All of this was a lot of info to take in. Even though I eventually would have to make a decision about the stomach cancer risk, the immediate question on the table was what to do about the breast cancer. After thinking about it, talking with the genetic counselor, the breast surgeon, the reconstructive surgeon and the medical oncologist (all in a short Memorial Day week), we decided to go ahead and do a double mastectomy on June 18.  By having the mastectomy, there was no need for either radiation or chemo.