Breast Cancer Screening Should Include Additional Genes

Newly-discovered gene mutations could double the risk of breast cancer.

Although BRCA 1/2 are the most well-known genes, there are many more that have been linked to the risk of breast cancer. Current genetic tests examine the presence of multiple gene mutations, but a new study published by Genetics in Medicine suggests that there are 2 more that should be included.

The study authors found that having the MSH6 or PMS2 gene mutations doubles the risk of breast cancer by age 60, which makes identifying these genes crucial for enhanced screening and prevention strategies.

Previously, it was understood that MSH6 or PMS2 can cause Lynch syndrome, which increases the risk of colorectal, ovarian, stomach, and endometrial cancers. This condition is associated with approximately 3% of newly diagnosed cases of colorectal cancer. The authors said that approximately 1 in 440 Americans have the mutation that causes Lynch syndrome, making it a fairly common condition.

It was unclear whether or not Lynch syndrome also increases the risk of breast cancer.

"People with Lynch syndrome aren't thinking they may also be at risk for breast cancer," said senior author Wendy Chung, MD, PhD. "Given the fact that genomic analysis is becoming more common in patients with a personal or family history of cancer, we have an opportunity to do more targeted breast cancer screening in women who carry any of the genes associated with risk for this disease."

Included in the study were data from more than 500,000 women who had received multi-gene hereditary cancer testing between 2013 and 2015. Of these patients, 423 had a mutation in 1 of the Lynch syndrome genes: MLH1, MSH2, MSH6, and PMS2.

Further analyses showed that women with MSH6 and PMS2 genetic mutations had a 2-fold higher risk of breast cancer compared with the general population, according to the study.

The authors applied their findings to the entire study population and projected that 31% to 38% of women with MSH6 and PMS2 mutations will develop breast cancer, according to the study. Comparatively, 15% of women in the general population will develop breast cancer.

"The new study suggests MSH6 and PMS2 should be added to the list of genes to screen for when there is a history of breast cancer," Dr Chung said. "Screening for these genes also would give these families potentially life-saving information to prevent colon cancer by encouraging individuals with the genes to increase the frequency of their colonoscopies."

The authors said that testing for Lynch syndrome is typically only conducted when a patient has a history of colon or uterine cancers.

Including the MSH6 and PMS2 variants to genetic testing may give patients a better understanding of their cancer risk and increase the chances of early diagnosis, according to the study.

"Given that Lynch syndrome is not rare in the general population, this finding has the potential to impact tens of thousands of people in the US and could change standard practice related to one of the most common cancer predisposition syndromes,” Dr Chung concluded.