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Hereditary Breast and Ovarian Cancer Syndrome (HBOC)

Hereditary breast and ovarian cancer syndrome (HBOC) is a rare genetic disorder that causes the development of multiple malignant (cancerous) tumours throughout the body. It is most commonly caused by a mutation in either BRCA1 or BRCA2 genes (breast cancer 1 or 2 respectively), however, other genes have also been linked to the disease.

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.

HBOC tends to affect the sexes equally, and is generally diagnosed before the age of 50. However, anyone can develop this disease.

HBOC is most commonly associated with the development of breast and ovarian cancers, however it has also been linked to other types of tumours. Some examples include:

Treatment

When cancers are detected, they are staged and graded based on size, metastasis, and how the cancer cells look under the microscope. Staging and grading helps your doctors determine the best treatment for you. However, each patient with HBOC will present with a unique disease behaviour, with varying tumour 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 benign (non-cancerous).
  • Tumour location.
  • Whether or not malignant tumours have metastasised.
  • Your age.
  • General health.
  • Your treatment preferences.

Your doctor may also recommend genetic testing, 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 HBOC may include:

  • Surgery to remove as much of the tumour(s) as possible – these will vary based on tumour type and location.
  • Chemotherapy.
  • Radiation therapy.
  • Targeted therapy.
  • Immunotherapy.
  • Hormone therapy.
  • Clinical trials.
  • Palliative care.

Cancer Screening

Once a diagnosis of HBOC has been confirmed, implementing a targeted 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 HBOC may include:

  • Monthly self-breast examinations in females.
  • Clinical breast examination every 6-12 months in females beginning at age 25.
  • Annual mammograms in females beginning at age 30.
  • Annual breast MRI beginning at age 25 in females (or earlier if breast cancer was detected in a relative before the age of 30).
  • Monthly self-breast examinations in males starting at age 35.
  • Annual clinical breast examination in males starting at age 35.
  • Annual serum prostate specific antigen (PSA) blood testing in males with BRCA2 mutation beginning at age 40.
  • Annual digital rectal examination in males with BRCA2 mutation beginning at age 40.

Screening options for HBOC 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

In most cases, HBOC is caused by a genetic mutation in either BRCA1 or BRCA2 genes, which are both tumour suppressor genes found in chromosomes 17 and 13 respectively. However, other genes can potentially also cause the disease, such as:

  • PALB2 (partner and localiser of BRCA2, tumour suppressor gene).
  • TP53 (tumour protein P53, tumour suppressor gene).
  • STK11 (serine/threonine kinase 11, tumour suppressor gene).
  • PTEN (phosphatase and tensin homolog, tumour suppressor gene).
  • CDH1 (cadherin 1, tumour suppressor gene).
  • MSH2 (mutS homolog 2, mismatch repair gene).
  • MLH1 (mutL protein homolog 1, mismatch repair gene).
  • MSH6 (mutS homolog 6, mismatch repair gene).
  • PMS2 (PMS1 Homolog 2, mismatch repair gene).
  • EPCAM (epithelial cell adhesion molecule, produces EpCAM protein and has close proximity to MSH2 gene, which may cause MSH2 to shut off in some cases).

HBOC 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 HBOC often vary by the type(s) of tumours present. General symptoms of HBOC may include:

  • 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.
  • Abdominal bloating/swelling.
  • Abdominal/pelvic pain and/or pressure.
  • Changes in appetite, such as feeling full quickly or not feeling hungry.
  • Changes in urination, such as:
    • Polyuria.
    • Feeling like your bladder isn’t empty after urination.
    • Slow urine flow.
    • Weaker bladder.
    • Loss of bladder control.
  • Changes in bowel habits, such as constipation and diarrhoea.
  • Unexplained weight loss or weight gain.
  • Unexplained fatigue.
  • Indigestion and/or heartburn.
  • Changes in menstrual periods, such as irregular periods, unusual vaginal bleeding, or vaginal bleeding post menopause.
  • Pain during sex.
  • Incontinence.
  • Blood in urine and/or semen.
  • Erectile dysfunction.
  • Pain when ejaculating.
  • Bone pain.
  • Jaundice.
  • Nausea and/or vomiting.

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 HBOC, 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 examination.
  • Genetic testing.
  • Pelvic examination.
  • Digital rectal examination (DRE).
  • Blood tests.
  • Imaging tests, potentially including:
    • Ultrasound.
    • MRI (magnetic resonance imaging).
    • CT (computed tomography) scan.
    • PET (positron emission tomography) scan.
    • Mammogram.
  • Exploratory procedures, such as an endoscopy.
  • Diagnostic laparoscopy.
  • Biopsy.

References

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