Genetic test uncovers risk of inherited breast cancer

A new gene-editing method can now determine whether certain genetic mutations raise a woman’s risk of breast and ovarian cancer.

The technique helps resolve a long-standing issue in genetic testing, where many patients receive inconclusive results showing “variants of unknown significance” – genetic changes that cannot be clearly linked to cancer risk.

Using the method, researchers have now classified 54 previously unconfirmed variants of the BRCA2 gene, identifying which ones are linked to disease and which are not.

Maria Rossing is clinical research associate professor at the University of Copenhagen’s Department of Clinical Medicine and chief physician at Rigshospitalet.

She said: “If we know a patient has a pathogenic mutation, we can intervene before the cancer has a chance to develop.

“For those already affected by the disease, we can treat them faster and more precisely. In the long run, this will save lives.”

The BRCA2 gene normally helps repair DNA damage. Mutations in this gene are known to increase the risk of several cancers, including breast, ovarian, pancreatic and prostate.

But until now, women carrying uncertain variants have often been unable to access appropriate preventive care.

The technique, developed by the University of Copenhagen and Rigshospitalet, uses CRISPR-Select – a form of gene-editing – to alter DNA in lab-grown cells and track how they respond to chemotherapy drugs.

The classification results are being added to international databases used by clinicians worldwide.

Rossing said: “It’s uncharted territory.

“Until now, we’ve only been able to inform patients that they have a mutation of unknown significance, and treating physicians haven’t been able to use that information in clinical decision-making.”

Women found to carry harmful variants can now be offered more targeted care, such as early screening or preventive surgery.

Rossing added: “When we can provide an accurate diagnosis, we can offer targeted treatment.

“For women who carry a disease-causing variant, we can offer preventive care through early detection and prophylactic surgery.

“But we can’t do that unless we know for sure whether a mutation leads to disease,” Rossing said.

The method combines gene-editing developed at the University of Copenhagen’s Biotech Research and Innovation Center with clinical testing at Rigshospitalet’s Department of Genomic Medicine.

Rossing said: “When researchers or doctors anywhere in the world search for these 54 variants in the databases, they’ll see our classification.

“This has implications far beyond Danish patients,”

Researchers hope the method will be used more widely to help classify thousands of other unknown variants, improving how hereditary cancer risk is assessed worldwide.