Value of Genetic Research for Drug Development: 2 Genes Identify Who Will Benefit from Breast Cancer Prophylaxis

June 2013, Vol 4, No 5

A new study supported by the National Institutes of Health Pharmacogenomics Research Network represents a step forward toward personalized medicine in breast cancer prevention among women who are at high risk for the disease.

“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,” said lead researcher James N. Ingle, MD, Professor of Oncology, Mayo Clinic, Rochester, MN. “We also discovered new information about how the drugs tamoxifen and raloxifene work to prevent breast cancer.”

Dr Ingle and colleagues analyzed genomic data from previous trials that included more than 33,000 women at high risk for breast cancer, investigating the more than 500,000 single nucleotide polymorphism (SNP) genetic markers. Of these SNPs, 2 genes were identified—ZNF423 and CTSO—which occurred more frequently in women who developed breast cancer during the trial than in the women who did not develop breast cancer.

This is the first time that the involvement of the ZNF423 and CTSO genes has been demonstrated in breast cancer. Women with either of these 2 genes were 5.7 times less likely to develop breast cancer while receiving preventive therapy with tamoxifen or raloxifene than women who did not have these genes.

“The results of our collaborative research bring us a major step toward the goal of truly individualized prevention of breast cancer,” Dr Ingle said. “Our findings also underscore the value of studying the influence of gene variations on drug responses.” National Institutes of Health; June 13, 2013

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