Familial Breast Cancer Management

Familial breast cancer is most commonly due to mutation in BRCA1 then BRCA2 genes. Patients with Li-Fraumeni syndrome are also susceptible.


Detection of BRCA1/2

There is no uniform finding on history or examination that confirms BRCA mutation. The prevelance in the normal population is about 0.3% or less. Testing is indicated when:

  • Patients have a strong family history of breast cancer. This can include:
    • Two first degree relatives with breast cancer
    • Three first or second degree relatives with breast cancer
    • Male relative with breast cancer
    • A relative with bilateral breast cancer
  • Patients with a strong family history of ovarian cancer (two cases in first or second degree relatives)
  • A relative with both breast and ovarian cancer
  • Relatives with either breast or ovarian cancer

There are also pathological findings which are suspicious for BRCA mutations. The most common tumour type is triple negative ductal carcinoma (80% of all BRCA tumours are this type, and 10-20% of triple negative tumours occur in patients with BRCA mutations), and the presence of this tumour should raise concern even without family history. The patient's age is also suggestive, particularly for women under 40.

Risks of BRCA1/2

Patients with BRCA1/2 are at highly susceptible to breast and ovarian cancers:

  • The lifetime risk of breast cancer is approximately 50% (slightly higher for BRCA1)
  • The lifetime risk of ovarian cancer is approximately 50% (BRCA1) to 20% (BRCA2)
  • Pancreatic cancers are also more frequent
  • Prostate cancer is more frequent, particularly associated with BRCA2.
  • Other cancers may also occur more frequently but data is scarce.

The average age is under 50.

BRCA1/2 breast cancer management

Breast conservation is just as effective for primary tumour control in BRCA1/2 positive patients, with similar rates of loco-regional control and disease specific survival. Radiotherapy is no more or less effective in treating these patients. The problem arises from the potential for new malignancies. The rate of contralateral breast cancer is approximately 25% within 10 years.
Approaches to management of BRCA1/2 positive patients generally involve:

  • Bilateral mastectomy, and bilateral salpingo-oophrectomy at completion of child bearing - this reduces the risk of new breast cancer developing by at least 90% in both sites.
  • Intensive surveillance with yearly mammograms, yearly breast MRI, monthly self-examination, quarterly medical examinations (for breast) and 6 monthly vaginal ultrasounds and CA-125 levels.
  • Chemoprevention with tamoxifen or aromatase inhibitors. There is limited direct evidence in BRCA mutation carriers but results are extrapolated from other chemoprevention trials of women at high risk. Tamoxifen for 5 years should halve the rates of malignancy developing. Oral contraceptive use reduces the risk of ovarian cancer.

Each approach must be discussed with patients. Younger patients who have not completed their family generally favour surveillance or chemoprevention.

Genetic Counselling

BRCA1/2 positivity does not only effect the patient but also their first degree, and potentially more distant, relatives. Informing relatives of the patient with a BRCA1/2 mutation is not mandantory. Both genes are inherited in an autosomal dominat fashion (ie. 50% risk of child receiving mutation). Therefore, genetic counselling should focus on:

  • Implications for the patient (need for further surgery, fertility, risks of new cancers)
  • Implications for the patient's children (prophylactic mastectomy, chemoprevention)
  • Implications for the patient's other relatives (similar for children but relatives are often older)