Nine years ago, Hollywood actress Angelina Jolie, shocked the world with her decision to have a bilateral risk-reducing mastectomy (BRRM), based on her genetic predisposition.
But this decision led to a massive awareness regarding genetic risk assessments for breast cancer.
Although genetic testing for breast cancer has been around for over three decades, it is constantly evolving. Today, we have panel-testing for no less than 84 genes available.
The BRCA1 and 2 gene tests are now well known (courtesy of Angelina Jolie). Using DNA analysis, it is possible to identify harmful changes (mutations) and develop appropriate risk management strategies.
A similar principal applies to other gene tests.
In developing countries (including South Africa), genetic testing is becoming more common as it has become more affordable and accessible.
Dr Justus Apffelstaedt, a specialist surgeon with an interest in breast, thyroid and parathyroid health as well as soft tissue surgical oncology, uses advanced genetic testing for risk assessment of healthy women and cancer patients alike.
His years of experience with the management of disease-causing BRCA gene mutations have shown that, after discussion of the different management strategies, most women choose their particular strategy based on their age:
- Age 0 – 18: No action
- Age 18 – 30: Surveillance: Annual breast imaging, ovarian cancer screening
- Age 30 – 50: Active surgical risk management: Risk reduction mastectomies followed a couple of years later by risk-reduction ovarectomies
- Age 50 - 70: Breast Imaging, ovarectomy
- Age 70+: Clinical management
As the evolution of gene testing continues, there are some impressive uses of available genetic testing for disease-causing mutations that can impact both breast cancer risk detection as well as the decisions regarding how individual cases should be managed.
The first example is the NBN gene. This gene provides instructions for making a protein called nibrin. This protein is involved in several critical cellular functions, including the repair of damaged DNA.
Similar to all other well-known cancer genes, there is a 50/50 random chance to pass on a NBN mutation to your sons and daughters.
Everyone has two copies of the NBN gene. Mutations in one copy of the NBN gene can increase the chance for you to develop certain types of cancer in your lifetime.
Genetic testing for this gene usually takes place at the diagnosis of breast cancer if familial history shows multiple cancer cases at a young age.
The treatment of the individual would be quite aggressive if this gene mutation is found at a young age; details will depend on the stage at which the cancer is diagnosed and the type of cancer.
As in other genes linked to an increased risk of breast cancer, a family work-up is imperative to put together risk reduction strategies for any other family members that carry the mutation.
Werner’s Syndrome is linked to another gene (the WRN gene) that also leads to an increased risk of suffering cancer.
This syndrome is generally known as the “adult early ageing” disease, where accelerated ageing takes place. Affected individuals have a short stature as well as other distinctive abnormalities such as lipodystropy (a change in fatty tissue) and accelerated atherosclerosis.
As with all other cancer-causing gene defects, defects in the WRN gene affect DNA repair negatively. While a family might just be seen as “short”, if there is a high cancer incidence, it is very worthwhile requesting a panel test, as this will include a number of cancer-related genes that might not be immediately obvious.
Another example is one of a family with multiple breast cancers and a known BRCA 2 disease-causing mutation. When one of the family members presented with a breast cancer, the obvious thought was that she also had inherited the family mutation.
A prior colon cancer however raised suspicions and on testing, the patient was found not to be carrier of the family mutation in the BRCA 2 gene, but of a disease-causing mutation in the MUTYH gene.
Defective MUTYH genes increase the risk of colon polyps and colorectal cancer, as well as breast and other cancers.
So, the breast cancer patient could also be counselled concerning her specific cancer risk management strategies and her side of the family assessed.
As can be seen, it is increasingly understood that gene testing in patients can provide hugely valuable information for treatment plans, risk management strategies for all cancers and can also, importantly, assist the family in understanding their own cancer vulnerabilities.
Gene testing is constantly evolving and its role in breast cancer is becoming increasingly important. It gives medical professionals a new level of information from which to determine management options and ultimately, allows for a more individualised approach to cancer.
The overall benefits to genetic testing
It is also becoming imperative that the treatment team should get as much information as possible about all cancers in the family, as that information can provide vital information that will guide which gene tests would be most useful.
Dr Justus Apffelstaedt, specialist surgeon with an interest in breast, thyroid and parathyroid health as well as soft tissue surgical oncology.