Genetic testing has become essential for assessing the risk of hereditary cancer, including breast cancer. However, the accuracy of these tests and their interpretation, particularly with regard to family history, can have a significant impact on clinical decisions.
This study aims to determine whether women with a family history of cancer are more likely to receive inflated risk assessments through genetic testing and, therefore, undergo unnecessary breast surgery.
Some women may choose to have unnecessary breast surgery to avoid cancer after being told they are at high risk based on genetic testing. However, these tests often do not take family history into account.
A recent study from the University of Exeter found that women who discover a pathogenic genetic variant in BRCA1 or BRCA2 outside of a clinical setting could be told they have a 60-80% risk of developing a breast cancer. But in reality, if they don’t have close relatives with the disease, their risk could be less than 20%.
This warning comes from research published in the journal Lancet eClinical Medicine. In the past, women who received BRCA results usually did so because they had symptoms or a family history of the disease. Risk calculations for specific BRCA variants were based on this group, which was already at high risk.
However, many people now use home DNA testing kits or receive results from genetic research, even if they have no personal connection to breast cancer. This new research, funded by the Medical Research Council, aimed to understand the risk of these BRCA variants in the general population.
In a study using data from the UK Biobank, researchers looked at more than 454,000 people aged 40 to 69. They found that having a pathogenic BRCA variant alone increased the risk of breast cancer to 18% (for BRCA2) and 23%. (for BRCA1) at the age of 60. If you had a close relative with breast cancer, the risk increased to 24% (for BRCA2) and 45% (for BRCA1).
Lead author Dr Leigh Jackson from the University of Exeter Medical School noted that more women were opting for breast cancer surgery, partly influenced by public figures like Angelina Jolie sharing their genetic testing and their surgical experiences. However, he emphasized that learning you have a high genetic risk can significantly affect your fear of a disease and your choices. A chance of up to 80% is very different from 20%. To make informed decisions, Dr. Jackson suggested that discussions about cancer risks should consider detailed family history, not just genetics.
He added, “If you are told that you are at high genetic risk for disease outside of a medical setting, it is best to talk to your doctor. They may consider various factors, including family history, to assess whether further investigation is necessary.
The study also looked at Lynch syndrome, a genetic disorder that increases the risk of colon and other cancers, and found a similar trend. The authors warned that widespread genetic testing for these conditions in the general population could lead many people to undergo unnecessary tests and procedures.
Co-author Professor Caroline Wright from the University of Exeter School of Medicine said: “Our findings will not only apply to breast and colorectal cancer. All genetic disease risk estimates are primarily based on relatively high risk groups who attend specialist clinics, so they will not necessarily translate to the general population.
This finding has significant ramifications for population screening using genome sequencing. We need to ensure that we carry out research to find the precise level of risk and be responsible in communicating risks, to avoid unnecessary fear and distress which could lead to avoidable procedures.
This study highlights the importance of accurately interpreting genetic test results, especially in people with a family history of hereditary cancers. Women who experience exaggerated risks from genetic testing are at risk of unnecessary breast surgery.
Health care providers should carefully consider family history when advising patients on the appropriate course of action, ensuring that surgical interventions are based on accurate risk assessments.
Journal reference:
- Leigh Jackson, Michael N. Weedon et al., Influence of family history on the penetrance of hereditary cancers in a population. eClinical Medicine. DOI: 10.1016/j.eclinm.2023.102159.
