Genetic testing

Breast cancer - Family history and genetic testing in New Zealand

The majority of breast cancers are described as sporadic because they develop spontaneously in an individual after the chromosomes in a cell are damaged by external factors such as radiation or chemical exposure. This damage allows the cell to multiply in an uncontrolled way. Further defects in the bodies regulatory systems must also occur to allow the cancer to grow and spread.

5% of breast cancer is thought to be due to an inherited abnormality. In these cases an abnormal gene has been passed on from the parents. This inherited abnormality means that the first step in the process of cancer transformation is already entrenched in the cell and therefore cancer is much more likely to develop. There are presumed to be many genes involved in the development of cancer. 2 specific genes have been identified that increase breast cancer risk. They are referred to as BRCA1 and BRCA2, and were first discovered in the early 1990s. Both of these genes code for proteins that are normally involved in repairing damage to the DNA of the cell and thereby stopping cancer from forming. If someone inherits an abnormal gene then this protein is defective and cannot do it's job properly. There is consequently a much higher risk of breast and ovarian cancer in people with this abnormality. Tests can be performed to identify these genetic abnormalities in women who have a strong family history of breast and/or ovarian cancer.

When to consider testing:

• (These are the recommendations of the NBCC of Australia)
• 2 or more first or second degree relatives with breast or ovarian cancer plus:
• Additional relatives with breast or ovarian cancer.
• Breast and ovarian cancer in same person
• Bilateral breast cancer
• Breast cancer in a male relative.
• Breast cancer diagnosed before age 40 years.
• Ovarian cancer diagnosed before age 50 years.
• Jewish ancestry.
• Member of family with confirmed BRCA abnormality.
• Note: A first degree relative is defined as mother, sister or daughter.
• A second degree relative is defined as aunt, nephew, niece, or grandparent.

Referal:

The Regional genetics service has offices in Auckland, Wellington and Christchurch.

Cost: free

The first step is an interview to collect details of the family history.

There will also be discussion about the implications of testing. This will cover questions such as:

• Do you actually want to know that you have a very high risk of developing a potentially fatal disease?
• How will your family react to this information?
• Will it create anxiety for other female family members?
• What about testing children in the family and discussing this risk with them?
• Will there be implications for future medical insurance or job applications?

Once a decision is made to proceed the process of genetic testing is complex and costly. The general approach is to first test an affected family member as the chance of finding an abnormal gene is higher in these individuals.If they test positive then other family members will be offered testing.

A blood sample is sent to an Australian laboratory. It may take 4- 6 months to get a result.

What does the result mean in practice?

If the BRCA test is negative you still have higher than normal risk of getting breast cancer because of the family history. It is presumed that there are other, as yet undiscovered genes that also contribute to breast cancer risk. You will need to consider lifestyle modifications to minimise risk and to have a breast surveillance plan for early detection.

If the test result is positive it does not mean that you will definitely get breast cancer, but your risk is substantially increased and may be as high as 80% in some cases. You will need to adopt lifestyle changes to reduce your risk and have a surveillance plan in place.

Breast surveillance will include regular clinical checks and imaging with ultrasound, mammography and possibly MRI scans.

Ovarian surveillance should be discussed with your gynaecologist. Options include transvaginal ultrasound and a blood test for a tumour marker called CA 125.

There are a number of prophylactic (risk reduction) strategies that can also be considered:

Prophylactic Tamoxifen: is thought to reduce risk of getting breast cancer by 30 - 50%. It is associated with a range of side effects ranging from hot flushes to increased risk of endometrial cancer and deep vein thrombosis.

Prophylactic oophorectomy (removal of the ovaries): In premenopausal women this procedure has a similar benefit to Tamoxifen in terms of risk reduction and also avoids the need for ovarian surveillance which is at best imprecise and unreliable.

Prophylactic mastectomy and breast reconstruction: This is a big operation, but available data suggests that it may reduce risk by up to 90%.  See case example

There is no need to rush into any of these decisions. Individual cases are best discussed in a multidisciplinary breast cancer meeting, and the woman should have seperate consultations with a number of specialists to get a balanced opinion on risks and benefits of these various options in her situation.