BRCA Genetic Test Results Might Lead to Unnecessary Surgeries: Study

In an era of readily available genetic testing, women who receive high-risk results for disease-causing variants in BRCA genes (BRCA1 or BRCA2) without considering their family history may be making life-altering decisions, including unnecessary surgeries to prevent breast cancer, warns new research led by the University of Exeter.

The study reveals that women told they have a disease-causing BRCA variant outside of a clinical setting might believe their risk of breast cancer is as high as 60-80% when it could be less than 20%, especially if they lack a close relative with the condition. 

This cautionary revelation emerges from a paper titled “Influence of family history on the penetrance of hereditary cancers in a population setting,” recently published in eClinicalMedicine. Traditionally, women who received BRCA genetic test results did so because they either had symptoms or had a family history of the disease. The calculation of breast cancer risk associated with certain BRCA variants was based on this inherently high-risk group. 

However, with the rise of home DNA testing kits and participation in genetic research studies, many individuals are now receiving such results without a personal connection to breast cancer. This research was conducted to provide a more accurate assessment of the true risk associated with these BRCA variants in the general population. 

The study analyzed data from over 454,000 participants aged 40 to 69 in the UK Biobank study, which collects DNA samples and gathers information about participants’ personal health and their family’s medical history. The findings revealed that merely carrying a disease-causing BRCA variant was linked to a breast cancer risk of 18% (for BRCA2) and 23% (for BRCA1) by age 60. However, having a close relative who had the condition elevated the risk to 24% (for BRCA2) and 45% (for BRCA1). 

Dr. Leigh Jackson, lead author and a member of the University of Exeter Medical School, highlighted that more women have been opting for breast cancer surgery, especially after actress Angelina Jolie shared her family history, genetic test results, and subsequent surgery. He emphasized the importance of accurate risk communication, stating, “Being told you are at high genetic risk of disease can really influence levels of fear of a particular condition and the resulting action you may take.

Up to 80% risk of developing breast cancer is very different from 20%. That difference could well influence the decision you make around whether you have invasive breast surgery.” He further added, “Some women may decide to go ahead with that procedure knowing that the risk is 20%, but we want them to make an informed decision. We’d urge that anyone communicating cancer risk does so based on a detailed family history, not just genetics alone.” 

The research team’s findings had broader implications when considering the genetic risk of Lynch syndrome, a condition that increases the risk of colon cancer and other cancers. They also concluded that genetic screening for these conditions in the general population might expose a significant number of individuals to unnecessary scans or procedures. 

Co-author Professor Caroline Wright, also from the University of Exeter Medical School, emphasized the need for responsible risk communication and accurate risk assessment. She stated, “Our findings will not just apply to breast and colorectal cancer. All risk estimates of genetic disease have so far largely been based on relatively high-risk groups who attend specialist clinics, so they will not necessarily translate to the general population.” 

Professor Wright concluded, “This finding has important ramifications for population screening using genome sequencing. We need to ensure we are carrying out research to find the true risk level and also to be responsible in how we communicate risk to avoid unnecessary fear and distress, which may lead to avoidable procedures.” 

For individuals receiving high genetic risk assessments for any disease outside of a clinical setting, consulting with a healthcare professional is strongly recommended. Healthcare providers can take into account a range of factors, including family history, to provide a more accurate assessment of the risk and recommend appropriate actions.