Diffuse gastric and lobular breast cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs syndrome (DGLBCS), formerly known as hereditary diffuse gastric cancer, is a rare genetic disorder that causes the development of multiple malignantcancerous, may grow and spread to other areas of the body (cancerous) tumours throughout the body. In particular, it is associated with an increased riskthe possibility that something bad will happen of developing diffuse gastric cancer and lobular breast cancer. It is caused by an alteration in the CDH1 or CTNNA1 genes.
Familial cancer syndromes, also known as hereditary cancer syndromes, are rare conditions that cause an increased risk of cancer as the result of inherited genetic mutations in certain cancer-related genes. They can affect both adults and children, however they generally develop in people at a younger age than normal. While familial cancer syndromes are not classified as cancer, they are equally as severe and can be life-threatening as they are associated with the development of various tumours throughout the body. Having a familial cancer syndrome does not guarantee the development of cancer, however the risk of developing cancer is higher than those who do not have a familial cancer syndrome.
DGLBCS tends to affect the sexes equally, and is generally diagnosed before the age of 40. However, anyone can develop this disease.
DGLBCS Related Tumours
DGLBCS is associated with the development of diffuse gastric cancer and lobular breast cancer only.
Diffuse gastric cancer is a rare type of adenocarcinomacancer arising from mucus-producing glands in organs (cancer arising from mucus-producing glands in organs) that forms in the lining of the stomach. It is also known as isolated cell-type carcinomacancer arising from tissues that line organs, or signet ring carcinoma, due to an unusually large cytoplasmic vacuoles that push the nucleus to the edge of the cell, forming a signet-ring shape. This type of cancer thickens the lining of the stomach; however, it does not form a distinct massa growth of cells that come together to make a lump, may or may not be cancer.
Lobular breast cancer occurs when abnormal cellsthe basic structural and functional unit of all living things are found in the lobules of the breasts. It can be confined solely to the lobules (referred to as lobular carcinoma in situpre-cancerous condition where abnormal cells haven't spread beyond the place they developed (LCIS)), or spread beyond the lining of the lobules (referred to as invasive lobular carcinoma (ILC)). This type of breast cancer is diagnosed almost exclusively in females, as male breasts do not generally contain lobes and lobules.
For more information on stomach (gastric) cancer or breast cancer, please refer to our knowledgebase.
Treatment
When cancers are detected, they are staged and graded based on size, metastasiswhen the cancer has spread to other parts of the body, also known as mets, and how the cancer cells look under the microscope. Stagingthe process of determining how big the cancer is, where it started and if it has spread to other areas and grading helps your doctors determine the best treatment for you. However, each patient with DGLBCS will present with a unique disease behaviour, with varying tumoura tissue mass that forms from groups of unhealthy cells locations and symptoms. As such, there is no one treatment method that will work for everyone, and there is no standard staging system for this disease. Instead of staging and grading, your doctor will recommend a treatment plan based on the following factors:
- Type of tumours present.
- Whether the tumours are malignant (cancerous) or benignnot cancerous, can grow but will not spread to other body parts (non-cancerous).
- Tumour location.
- Whether or not malignant tumours have metastasised.
- Your age.
- General health.
- Your treatment preferences.
Your doctor may also recommend genetic testinga procedure that analyses DNA to identify changes in genes, chromosomes and proteins, which can be used to analyse tumour DNA to help determine which treatment has the greatest chance of success, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. They will then discuss the most appropriate treatment option for you.
Treatment options for tumours associated with DGLBCS may include:
- Surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence, potentially including:
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- Gastrectomycomplete or partial removal of the stomach.
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- Lymphadenectomysurgical removal of lymph node(s).
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- Surgery to insert a feeding tube (often required after surgery on the stomach), such as a gastronomy tube (G-tube)a feeding tube surgically inserted through an incision in the abdominal wall directly into the stomach to get fluids/food/liquids to and from the stomach or a nasogastric tube (NG tube)a thin, soft tube that goes in through the nose, down the throat, and into the stomach to get fluids/food/liquids to and from the stomach, also known as a NG tube.
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- Lumpectomya surgical procedure where the tumour and a small amount of surrounding breast tissue are removed, also known as breast conserving surgery, also known as breast-conserving surgerya surgical procedure where the tumour and a small amount of surrounding breast tissue are removed, also known as a lumpectomy.
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- Unilateralaffecting one side or bilateralaffecting both sides mastectomycomplete or partial removal of one or both breasts.
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- Breast reconstructiona surgery to recreate a natural-looking breast after a mastectomy.
- Chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells.
- Radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells.
- Hormone therapymedication that alters the levels of certain hormones in the body, such as oestrogen and progesterone.
- Targeted therapymedication that targets specific molecular features of cancer cells.
- Clinical trialsresearch studies performed to test new treatments, tests or procedures and evaluate their effectiveness on various diseases.
- Palliative carea variety of practices and exercises used to provide pain relief and improve quality of life without curing the disease.
Cancer Screening
Once a diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results of DGLBCS has been confirmed, implementing a targeted screeningtesting for cancer or conditions that can lead to cancer before symptoms appear, also known as cancer screening plan becomes essential due to the increased risk of developing certain cancers. The content of this plan will vary from person to person based on the genetic mutation involved, your family’s history of cancer and the types of cancers that may be present. It will also outline the routine tests you should have and how regularly you should have them. Some recommendations for DGLBCS may include:
- Gastroscopyexamination of the stomach and part of the small bowel with a small, flexible instrument known as a gastroscope every 6-12 months beginning at age 40 or 5-10 years before the earliest gastric cancer diagnosis in the family with a minimum age of 18 years old.
- Monthly self-breast examinations beginning at age 20.
- Annual clinical breast examinations and bilateral breast MRI beginning at age 30.
- Annual mammograms (between breast MRIs) beginning at age 30-40.
Screening options for DGLBCS may evolve as new technologies are developed and our understanding of the condition grows. It is essential to discuss your individual circumstances with your healthcare team to determine the most appropriate screening plan for you.
Risk factors
DGLBCS is caused by a genetic mutation in one of the following genes:
- Cadherin-1 (CDH1) gene.
- Alpha catenin (CTNNA1) gene.
Both CDH1 and CTNNA1 play a crucial role in cell-to-cell adhesion and maintaining tissuea group of cells that work together to perform a function structure in epithelial tissue. DGLBCS is an autosomal dominant disorder, which means that you have a 50% chance of developing the condition if one of your parents carries the mutation.
Symptoms
The symptoms of DGLBCS often vary by the type(s) of tumours present. General symptoms of DGLBCS may include:
- Unexplained weight loss and/or loss of appetite.
- Difficulties swallowing.
- Indigestion, which may carry its own set of symptoms:
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- Abdominal pain/burning.
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- Heartburn.
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- Frequent burping.
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- Reflux.
- Nauseato feel sick or likely to vomit and/or vomiting.
- Abdominal pain.
- Feeling full after eating small quantities of food.
- Abdominal swelling and/or bloating.
- Fatiguea state of extreme tiredness or exhaustion, can be physical or mental.
- Anaemiaa condition where there aren't enough red blood cells in the blood, causing fatigue, weakness and pale skin and affecting how the body responds to infection.
- Vomit with bloodthe red bodily fluid that transports oxygen and other nutrients around the body in it.
- Discoloured stools.
- A lump or lumpiness in the breast(s).
- A change in the size and/or shape of the breast.
- Swollen breasts.
- Changes to the nipple.
- Dimpling or indentation on the skin of the breast.
- A rash and/or itchiness of the breast.
- A scaly appearance and/or changes in the colour of the breast.
- Swelling or discomfort in the armpit or near the collarbone.
- Persistent, unusual pain not associated with the menstrual cycle.
Symptoms related to specific tumours can be found on our knowledgebase.
Not everyone with the symptoms above will have cancer, but see your general practitioner (GP) if you are concerned.
Diagnosis
If your doctor suspects you have tumours associated with DGLBCS they may order some of the following tests to confirm the diagnosis and refer you to a specialist for treatment. The tests required for diagnosis will often vary based on the symptoms present, and where the tumour(s) are suspected to be located.
- Physical examinationan examination of your current symptoms, affected area(s) and overall medical history.
- Genetic testing.
- Blood teststesting done to measure the levels of certain substances in the blood.
- Imagingtests that create detailed images of areas inside the body tests, potentially including:
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- Mammograma type of medical imaging that uses x-rays to create detailed images of breast tissue.
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- Ultrasounda type of medical imaging that uses soundwaves to create detailed images of the body .
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- MRI (magnetic resonance imaging)a type of medical imaging that uses radiowaves, a strong magnet and computer technology to create detailed images of the body.
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- CT (computed tomography) scana type of medical imaging that uses x-rays and computer technology to create detailed images of the body.
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- PET (positron emission tomography) scana type of medical imaging that uses radioactive tracers to create detailed images of the body.
- Endoscopya procedure that involves inserting a long, flexible tube with a light and small camera (endoscope) into the body to view internal organs, most commonly a gastroscopy.
- Biopsyremoval of a section of tissue to analyse for cancer cells.