Genes may help guide use of preventive breast cancer drugs

Volume 2, Issue 3, 2013


Women with favorable variations in certain genes are more likely to respond to preventive therapy.

Photograph showing James N. Ingle, M.D., a Mayo Clinic Cancer Center oncologist

James N. Ingle, M.D.

Recently discovered genetic variations may help predict breast cancer risk in women who receive preventive breast cancer therapy with tamoxifen and raloxifene, according to a Mayo Clinic Cancer Center-led study.

"Our findings are important because we identified genetic factors that could eventually be used to select women who should be offered the drugs for prevention," said James N. Ingle, M.D., an oncologist with the Mayo Clinic Cancer Center.

Dr. Ingle and collaborators at the National Surgical Adjuvant Breast and Bowel Project (NSABP) and the RIKEN Center for Genomic Medicine conducted a genome-wide association study involving 592 patients who developed breast cancer while receiving preventive therapy and 1,171 matched controls. Participants were selected from 33,000 women enrolled in the NSABP breast cancer prevention trials.

The researchers analyzed participants' DNA to identify variations in their genetic makeup. They identified two genetic variations, or single nucleotide polymorphisms, that were associated with breast cancer risk in or near the genes ZNF423 and CTSO.

The researchers discovered that women with favorable variations in these genes were more likely to respond to preventive therapy with the drugs, while women with unfavorable variations may not. In addition, women with unfavorable variations had a fivefold increased risk of developing breast cancer.

Dr. Ingle says that recent guidelines by the U.S. Preventive Services Task Force emphasize that selective estrogen receptor modulator therapy with tamoxifen and raloxifene can lower a woman's risk of developing breast cancer. However, there currently is no way to know which women will benefit from the therapy.

"This is a major step toward truly individualized prevention of breast cancer," Dr. Ingle said. "Our findings provide clear direction as to which women are likely and which are unlikely to benefit from tamoxifen or raloxifene." The findings provide the basis for a reinvigoration of research efforts in breast cancer prevention, he said.

The study was published in the June 13, 2013, edition of the journal Cancer Discovery.