Who should be referred for genetic testing?
Individuals who are potentially at high risk can be referred to their regional branch of Genetic Health Service NZ (GHSNZ) and to a breast specialist for a full assessment of their risk. GHSNZ is part of New Zealand’s public health system and operates clinics throughout the country. These are situated in regional hubs at three major hospitals. Outreach clinics are also provided at other regional hospitals according to demand.
- Northern Hub: This service, based at Auckland City Hospital, covers the upper half of the North Island with outreach clinics in Whangarei, Hamilton, Tauranga, Rotorua and Gisborne.
- Central Hub: Based at Wellington Hospital. This service covers the lower half of the North Island and Nelson. Outreach clinics are provided in New Plymouth, Whanganui, Hastings, Palmerston North, Porirua, Lower Hutt and Nelson.
- South Island Hub: Based at Christchurch Hospital. This service covers all of the South Island except Nelson. Outreach clinics are provided in Blenheim, Greymouth, Timaru, Dunedin, Queenstown and Invercargill.
GHSNZ’s clinical geneticists and genetic counsellors would make a risk assessment and, if appropriate, arrange genetic testing. The breast specialist will arrange surveillance and discuss possible measures for risk reduction.
Anyone fitting the following criteria warrants referral to Genetic Services for assessment. If one of the following applies to you, ask your GP about a referral .
Untested adult blood relatives of a person with an identified mutation in a breast and/or ovarian cancer predisposition gene (e.g. BRCA1, BRCA2, TP53, PTEN, STK11).
- Triple negative breast cancer (ER, PR and HER2 negative) diagnosed under the age of 50
- High-grade, non-mucinous, epithelial ovarian, fallopian tube or primary peritoneal cancer
- Lobular breast cancer AND a family history of lobular breast or diffuse-type stomach cancer
- Breast cancer diagnosed under 40
- Male breast cancer diagnosed at any age
- Breast and ovarian cancer primary cancers at any age
- Two primary breast cancers where the first occurred under 50
- Breast cancer plus personal or family history of:
- Peutz Jegher syndrome
- PTEN hamartoma syndrome
- Li Fraumeni syndrome.
Two first- or second-degree relatives diagnosed with breast or ovarian cancer, plus one or more of the following on the same side of the family:
- Additional relative(s) with breast or ovarian cancer
- Breast cancer diagnosed under 50
- More than one primary breast cancer in the same woman
- Breast and ovarian cancer in the same woman
- Ashkenazi (Eastern European)Jewish ancestry
- Male breast cancer.
Note: First-degree relatives are parents, siblings and children. Second-degree relatives are: grandparents, aunts and uncles, nephews and nieces, grandchildren, and half-siblings.
These recommendations are taken from the EVIQ protocols, which are followed by Genetic Services NZ.
Genetic counselling and testing
Genetic counselling is recommended before genetic testing to properly assess an individual’s true risk and after testing to discuss the significance of results and advise on strategies to manage them.
Before any testing can take place a genetic counsellor will help you map your family structure and history on both the maternal and paternal sides. This needs to span three generations and each cancer diagnosis in the family must be confirmed.
If your level of risk meets the criteria for testing, the counsellor will discuss the implications of testing with you so you can make an informed decision about whether or not to proceed. For example:
- What are the implications of a positive result? A negative result?
- What if the test doesn't return a definite result?
- What are the psychological risks and benefits of being tested?
- What are the implications for insurance if a mutation is found?
Harmful gene mutations are relatively rare in the population and they are extremely difficult to detect and interpret, especially in an individual who doesn’t have cancer.
Genetic testing is a complex process and geneticists could find a genetic mutation which has not previously been associated with cancer. This type of test result is reported as “a genetic variant of uncertain significance” because it isn’t known whether this particular gene mutation affects a person’s risk of developing cancer.
There are many gene variants of unknown significance, so it is more useful to test a family member who does have cancer, to see if this has been caused by a specific, known cancer-causing mutation. This is why an affected family member is offered testing first and wider family members are offered counselling and testing only if a mutation is confirmed.
How does the test work?
A genetic test involves taking a blood sample for analysis. Results can take several weeks but can sometimes be done more urgently for an affected person if cancer treatment would likely be altered by a positive result.
Genetic test results
A positive or negative result could be given when there is a known disease-causing gene change in the family.
A positive result indicates that the person has inherited a harmful mutation in BRCA1 or 2, or perhaps another high-risk mutation, and has an increased risk of developing breast/ovarian cancer.
However, the test can’t predict whether the person will actually go on to develop cancer.
If the mutation is definitely present then that person has inherited it from a parent and may pass it on to their own sons and daughters even if they don’t develop cancer themselves. The result means that their full siblings have a 50% chance of also having the mutation.
A negative result can only be given if a known mutation has already been identified in a blood relative and testing does not reveal that mutation in the individual being tested. This means that the person has not inherited that mutation and is at the same risk as the general population.
A genetic test may return an inconclusive or uncertain result.
An inconclusive result means that a genetic test on an affected individual has not detected any gene alterations. This reduces the likelihood of a BRCA1 or BRCA2 mutation, but it does not completely eliminate it. A mutation may have been missed with the current testing strategy, or the individual’s diagnosis and/or family history is due to another gene change that was not tested for or has not been identified yet.
A variant result is referred to as a genetic variant of uncertain significance. A variant mutation on BRCA1 or 2 is identified but it’s not currently known whether the particular mutation carries an increased cancer risk. It also can’t be used to determine the risk for relatives of the individual who has been tested. Over 1600 different mutations have been identified on BRCA1 and 2 and most of them are of uncertain clinical significance.
As knowledge of these variants expands, some may eventually be reclassified as either harmful or benign.
If you have no family member with a confirmed mutation but your family history is very strong, suggesting the possibility of a mutation, then anything other than a positive test result is also referred to as inconclusive. This means you could have a harmful mutation which is not currently able to be identified.
If you do have a confirmed cancer-causing mutation, you might want to take action to reduce your breast cancer risk. Talk to your genetic counsellor and medical team about which options suit your situation. Find out more about risk-reducing options.