New Developments in Managing Hereditary Gastric Cancer
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For a person with hereditary stomach (or gastric) cancer, a prophylactic gastrectomy is usually recommended when it comes to managing your gastric cancer risk. However, removing the whole stomach is a big and drastic change that affects many people physically and mentally. In this article, we take a look at some new developments in the management of hereditary gastric cancer so that a prophylactic gastrectomy is only recommended when absolutely necessary.
What does knowing you have hereditary cancer feel like?
Imagine you're going about your day, minding your own business, when someone sneaks up behind you.
You feel something pressing, hard, into the back of your head. You start to tremble.
Then, someone whispers in your ear....
"Sssshhhhh.... don't turn around. Just listen. I am holding a gun against the back of your head. I'm going to keep it there. I'm going to follow you around like this every day, for the rest of your life."
"I'm going to press a bit harder, every so often, just to remind you I'm here, but you need to try your best to ignore me, to move on with your life. Act like I'm not here, but don't you ever forget... one day I may just pull the trigger... or maybe I won't. Isn't this going to be a fun game?"
—Sherry McAllister, two-time cancer survivor
What Sherry described is an experience that is especially true for those with hereditary cancers. In an NPR article, the news director of Boise State Public Radio, Sasa Woodruff, shared how she found out that her CDH1 mutation could lead to gastric and breast cancers.
As Sasa had a strong family history of cancer, she was tested for BRCA1/2 mutation, the infamous gene that led to Angelina Jolie getting a double mastectomy. Her result came back negative. But years later, she received an email from Dr. Richard Frieder, who introduced himself as the medical director at Intelegene Cancer Genetics.
The email read:
An email Sasa Woodruff received from the medical director at Intelegene Cancer Genetics.
Source: NPR
Hereditary gastric cancer and how it’s managed
A mutation in the CDH1 gene can elevate a person’s lifetime risk of developing diffuse gastric cancer by up to 70% and lobular breast cancer (39-55%) for women.
> Learn more about hereditary diffuse gastric cancer, which is caused by the CDH1 gene mutation
According to the 2020 version of the International Gastric Linkage Consortium (IGCLC) guidelines for individuals with pathogenic CDH1 gene mutation, hereditary gastric cancer can be prevented by prophylactic gastrectomy. This refers to the total removal of the stomach via surgery.
"The recommended treatment is stomach removal,” said Sasa’s genetic counselor while handing her a brochure entitled ‘No Stomach For Cancer’.
Like Sasa, individuals with germline (inherited or hereditary) CDH1 mutations face difficult decisions when it comes to cancer screening and risk-reducing surgeries.
While the risk of CDH1 mutation-causing stomach (gastric) cancer poses uncertainty, removal of the entire stomach is surely traumatic to many. Nonetheless, there are advances in gastric cancer screening that improve cancer monitoring and prevention.
Improvements in the management of hereditary gastric cancer
Advancements in endoscopic techniques for surveillance
Advancements in endoscopic techniques, such as the use of high definition white light and chromoendoscopy, can enhance imaging and potentially improve the detection of malignant lesions. One example is a novel imaging technology called confocal endoscopic microscopy (CEM), which produces ultra-high magnification and allows for real-time, in vivo histological analysis of the gastrointestinal mucosa during an upper endoscopy.
Surgeon using the cell viZio imaging system, which allows microscopic images of tissue to be taken during an endoscopy. Both the normal endoscope image (left) and the microscopic image of the tissue (right) can be seen. Source: Philippe Psaila/Science Photo Library
CEM is being studied as an important complement to existing imaging techniques, in order to avoid unnecessary biopsies during routine endoscopic surveillance and thereby improve monitoring in people with hereditary gastric cancer.
Liquid biopsy techniques to monitor early-stage gastric cancer
Researchers in Japan, where the incidence of gastric cancer is high, have even suggested the potential use of liquid biopsy techniques to identify and monitor early-stage gastric cancer before prophylactic surgeries are considered. However, prophylactic gastrectomy would still be recommended based on the person’s risk level, especially for high-risk individuals with the CDH1 gene mutation.
Amongst the various liquid biopsy detection tests is GASTROClearTM, the world’s first non-invasive gastric cancer screening test produced by MiRXES Singapore. The test has a proven 82% sensitivity and 88% specificity in detecting asymptomatic gastric cancer. It has obtained European CE Marking for In Vitro Diagnostic (IVD) devices and granted Breakthrough Device Designation by the United States Food and Drug Administration (FDA).
> Learn more about GASTROClear here
Chemoprevention
Apart from cancer monitoring techniques, researchers are looking into the use of medication, vitamins and supplements to stop the development of gastric cancer in people with hereditary gastric cancer. This is known as chemoprevention. One promising candidate drug is Entinostat, a histone deacetylase inhibitor to which cells or organoids with the infamous CDH1 mutation showed greater sensitivity.
Scientists are planning to investigate the use of Entinostat in combination with other potential chemoprevention drugs, with the aim of identifying synergistic drug combinations that can prevent gastric cancer in people carrying the CDH1 gene mutation.
