Fergus Couch, Ph.D., Discusses Breast-Cancer Gene Mutations
According to a recent article in The Atlantic, newly discovered BRCA1 mutations known as “variants of unknown significance” (or VUS) could be harmful, making a woman’s risk of developing breast cancer as high as 72%. Or, it could be nothing to worry about at all.
According to Fergus Couch, Ph.D., Chair of the Division of Experimental Pathology and Laboratory Medicine, “You hear these horror stories about people who have a VUS,” says Fergus Couch, a breast-cancer researcher at Mayo Clinic. “They have the surgery”—to preemptively remove their breasts—“because they’re convinced the VUS is actually pathogenic, but then we find out later that it is neutral.” The invasive surgery was never necessary at all. However, the opposite can also be true: A variant that looks neutral could turn out to be pathogenic.
For this reason, researchers have spent decades since BRCA1’s discovery trying to catalog its many variants. BRCA1 is a tumor-suppressing gene, and only certain mutated forms are associated with high cancer risk. Theoretically, there could be thousands of variants. And even once a new variant has been identified, it may be so rare that doctors never gather enough data in patients to understand its associated breast-cancer risk.
In the article, Dr. Couch also discusses how his frequent research collaborator Alvaro Monteiro at Moffitt Cancer Center has been analyzing mutations in BRCA1 one by one in cells growing in a laboratory. Over 15 years, he’s looked at 300 to 350 variants. His analysis has been more carefully validated against actual patient data.
According to Dr. Couch, doctors are hesitant to base patient decisions only on data from cells growing in a lab. “There’s a degree of caution.” But for some rare VUS, that may be the best they have.