Gene variants may predict who will benefit from breast cancer prevention drugs

June 21, 2013

In women at high risk for breast cancer, a long-term drug treatment can cut the risk of developing the disease in half. Researchers supported by the National Institutes of Health have now identified two gene variants that may predict which women are most likely to benefit from this therapy—and which should avoid it. The work represents a major step toward truly individualized breast cancer prevention in women at high risk for the disease based on age and family and personal medical history.

“Our study reveals the first known genetic factors that can help predict which high-risk women should be offered breast cancer prevention treatment and which women should be spared any unnecessary expense and risk from taking these medications,” says the study's lead scientist, James N. Ingle, MD, professor of oncology at the Mayo Clinic. The research, which shows nearly a six-fold difference in disease risk depending on a woman's genetic makeup, appears in Cancer Discovery.

The investigators leveraged data from past NSABP breast cancer prevention trials that involved more than 33,000 high-risk women. They analyzed the genomic data by focusing on more than 500,000 genetic markers called single nucleotide polymorphisms (SNPs). Each SNP represents a single variation in the DNA sequence at a particular location within the genome.

To determine whether any SNPs were associated with breast cancer risk, the researchers computationally searched for SNPs that occurred more commonly in women who developed breast cancer during the trial than in women who remained disease-free. The analysis identified two such SNPs—one in a gene called ZNF423 and the other near a gene called CTSO. Read the study abstract.