A recent article in JAMA Internal Medicine describes a common genetic mutation found in many breast cancer patients who do not have a family history of the disease. The study looked at germline pathogenic variants (GPVs), which are DNA changes that can cause disease. GPVs are passed down through reproductive cells, so they are present in every cell of the body. Many GPVs are known to raise a person’s risk of cancer. Finding these variants helps doctors develop better screening methods to spot high-risk patients and monitor them more closely.
The study analyzed data from more than 23,000 women who took part in the Women Informed to Screen Depending on Measures of Risk (WISDOM) clinical trial. This large, multi-center trial compared two types of breast cancer screening: age-based screening, where all women over 40 get yearly mammograms, and risk-based screening, where mammogram recommendations depend on risk factors like family history or genetics.
The researchers aimed to identify the prevalence of GPVs and determine if positivity relates to family history of breast cancer. Women received germline testing for nine known breast cancer susceptibility genes, tumor suppressor genes that, if mutated, significantly increase the lifetime risk of breast cancer.
Out of 23,098 women who had genetic screening, 3.1% had a GPV. The most common mutations were found in the CHEK2 and ATM genes.
The researchers looked at several factors to define family history, such as breast or ovarian cancer in close female relatives, a male relative with breast cancer, or Jewish ancestry. They found that almost 30% of women with GPVs did not report a family history of breast cancer.
The study found many women with GPVs who would not have been eligible for genetic testing under current guidelines. The results suggest that doctors and policy makers should consider adding genetic testing to breast cancer screening protocols.
Sources: JAMA Int Med, Cell
