Gynecology Book


Breast Cancer Gene Marker

Aka: Breast Cancer Gene Marker, BRCA, Breast Cancer Gene Marker Testing Indications
  1. See Also
    1. BRCA1
    2. BRCA2
  2. Labs: Gene Markers
    1. Most common types (>20 mutations have been identified)
    2. BRCA (BRCA1, BRCA2): 60% of Breast Cancer gene mutations
      1. BRCA mutation Prevalence: 1 in 400 overall (1 in 40 in Ashkenazi jewish heritage)
      2. Autosomal Dominant inheritance
    3. AT (Ataxia Telangiectasia) on Chromosome 11
      1. Single mutant copy
      2. Confers 5 fold risk of Breast Cancer
    4. PTEN gene (Cowden syndrome)
    5. CDH1 gene (hereditary diffuse Gastric Cancer)
    6. TP53 gene (Li-Fraumeni syndrome)
    7. STK11 gene (Peutz-Jeghers Syndrome)
  3. Indications: BRCA testing (>5 to 10% pretest probability)
    1. Person with Family History of Breast Cancer or Ovarian Cancer and known BRCA mutation
    2. Ashkenazi jewish women
      1. 1st degree relative with Breast or Ovarian Cancer or
      2. Two 2nd deg. relatives with Breast or Ovarian Cancer
    3. Non-Ashkenazi women
      1. First degree relatives
        1. Two with Breast Cancer (at least 1 under age 50)
        2. One with bilateral Breast Cancer
      2. First or second degree relatives
        1. Three with Breast Cancer
        2. Comorbid Breast and Ovarian Cancer at any age
        3. Two or more with Ovarian Cancer
      3. Extended family
        1. Breast Cancer in any male relative (third degree or closer)
    4. Personal history of Breast Cancer
      1. Breast Cancer diagnosed at age <45 years
      2. Breast Cancer diagnosed at age <50 years AND at least one additional criteria
        1. At least one blood relative (third degree or closer) with Breast or Ovarian Cancer (or variants)
        2. Two primary Breast Cancers
        3. Limited Family History
      3. Breast Cancer diagnosed at age <60 years AND at least one additional criteria
        1. Triple negative Breast Cancer
      4. Breast Cancer diagnosed at any age AND at least one additional criteria
        1. Ethnicity with high mutation frequency (e.g. Ashkenazi Jewish)
        2. Personal history or Family History (third degree or closer) of male Breast Cancer
        3. At least two blood relatives (third degree or closer) on same side of family AND one of the following
          1. Breast or Ovarian Cancer (or one at age <50 years)
          2. Pancreatic Cancer or aggressive Prostate Cancer (Gleason>=7)
    5. Personal history of other cancers
      1. Personal history of epithelial ovarian, fallopian or primary peritoneal cancer
      2. Pancreatic Cancer or aggressive Prostate Cancer (Gleason>=7)
  4. Management: Known BRCA1 or BRCA2 carrier
    1. BRCA1 Lifetime Risks
      1. See BRCA1
      2. Breast Cancer in Women: 50-80%
        1. Second primary Breast Cancer 27% within 5 years
      3. Breast Cancer in Men: 1 to 2%
      4. Ovarian Cancer risk: 18 to 40% (up to 54% in some studies)
      5. Prostate Cancer: <30%
      6. Pancreatic Cancer: 1 to 3%
    2. BRCA2 Lifetime Risks
      1. See BRCA2
      2. Breast Cancer in Women: 40 to 70% (up to 90% in some studies)
        1. Second primary Breast Cancer 12% within 5 years (40 to 50% at 20 years)
      3. Breast Cancer in Men: 5 to 10%
      4. Ovarian Cancer risk: 11-20%
      5. Prostate Cancer: <40%
      6. Pancreatic Cancer: 2 to 7%
      7. Melanoma
    3. Breast Cancer Risk Management in Women
      1. Surveillance starting at age 25 years
        1. Self Breast Exam Monthly (start at age 18 years)
        2. Clinical Breast Exam every 6 months
        3. Breast MRI with contrast yearly (start at age 25 years)
          1. May perform Mammogram as an alternative to MRI for age 25 to 30 years
          2. As of age 30 years, perform MRI and Mammogram
        4. Mammogram yearly (start at age 30 years)
          1. Perform BOTH MRI and Mammogram as of age 30 years
      2. Prophylactic Mastectomy
        1. Breast Cancer can still occur
      3. References
        1. Garber in Harris (1996) Diseases Breast p. 335-41
    4. Ovarian Cancer Risk Management
      1. No clear evidence-based guidelines
        1. Screening typically identifies Ovarian Cancer in late stages (stage 3 and 4)
        2. Prophylactic Oophorectomy is the most effective strategy
      2. NCCN guidelines (esp. BRCA1) for intact ovaries
        1. Test every 6 months from age 35
        2. Tests
          1. Transvaginal Ultrasound
          2. CA-125
    5. Men with BRCA positive status
      1. Self Breast Exam monthly starting at age 35 years
      2. Mammogram (if enough Breast tissue or Gynecomastia to allow for Mammogram)
        1. Start yearly at age 50 years (or 10 years before youngest relative with Breast Cancer)
      3. Prostate Cancer Screening starting at age 40 years (BRCA2)
      4. Melanoma skin cancer screening
        1. Annual full body skin exam
        2. Skin Cancer Prevention (Sunscreen and other measures to reduce UV exposure)
  5. References
    1. Lypas (2018) Forum of Clinical Oncology 7(2): 16-24
    2. Casaubon (2022) BRCA 1 and 2, StatPearls, Treasure Island +PMID: 29262038 [PubMed]
    3. Daly (2021) J Natl Compr Canc Netw 19(1): 77-102 [PubMed]

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