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Etiology of Breast Cancer

There is still lack of knowledge of the direct etiology of breast cancer development.

Risk factors

  • Hereditary
  • Sex
  • Hormonal circumstances (early menarche, late first-time birth, nullparity, and late menopause)
  • Atypical hyperplasia
  • Ionizing radiation
  • Estrogen use before 35 years
  • Protacted post-menopausal estrogen therapy
  • Previous breast cancer
  • Obesity, particularly combined with tallness (high BMI, especially > 30)
  • Alcohol, even in moderate amounts

Not all risk factors are equally important.

Factors reducing the risk

  • First pregnancy < 20-25 years
  • Multiple pregnancies < 25 years
  • Breastfeeding (15)
  • Asian descent
  • Regular exercise

Hereditary breast cancer

It is estimated that 5-10% of breast cancer cases is due to inheritance in the close family (first degree relatives such as mother, daughter, sister or grandmother).

BRCA1 and BRCA2 belong to a class of genes known as tumor suppressors. In normal cells BRCA1 and BRCA2 contributes to ensure the stability of the cell's genetic material (DNA) and prevent uncontrolled cell growth. Mutations in these genes raises risk of both breast and ovarian cancer.

In families with hereditary breast and ovarian cancer a mutation in one of the BRCA genes is common. Most families with accumulation of breast cancer have not simultaneous ovarian cancer, and there is usually not BRCA gene mutations. The reason for the accumulation of breast cancer in these families is not known. It is assumed to be caused by mutations in (so far) unknown genes. Almost all people with gene mutations belong to families who have had these mutations for a very long time. A gene analysis (Decaplex assay) detects these gene mutations. This genetic test will detect at least 50% of those with BRCA gene mutations in Norway, perhaps as much as 75%.

In addition to the few frequent BRCA gene mutations, there are a number of rare BRCA gene mutations. A normal gene analysis for frequent gene mutations does not exclude hereditary cancer or BRCA gene mutations. About one-third of patients with familial breast cancer have detectable BRCA gene mutations if one examines both genes completely, while almost all families with accumulation of both breast and ovarian cancer have detectable BRCA gene mutations. There is a transition now from rapid testing to complete analysis of genes (using modern sequencing techniques).

It is estimated that about 2% of patients with breast cancer have BRCA gene mutations. 

Criterias for referral to clinical geneticist

  • Proven gene mutation in the breast cancer patient
  • Accumulation of cancer in the family
    • Two sisters or mother-daughter with breast cancer before 50 years
    • Multiple instances of breast cancer in the family
    • Both breast and ovarian cancer in the family

One should be aware of breast and ovarian cancer where kinship is through men.

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