June 13, 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 their age, family history of breast cancer, 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," said the study's lead scientist, James N. Ingle, M.D., professor of oncology at the Mayo Clinic in Rochester, Minn. "We also discovered new information about how the drugs tamoxifen and raloxifene work to prevent breast cancer."

Ingle and Mayo-based colleagues in the NIH Pharmacogenomics Research Network (PGRN) conducted the study in collaboration with PGRN-affiliated researchers at the RIKEN Center for Genomic Medicine in Tokyo. Data and patient DNA came from the long-running National Surgical Adjuvant Breast and Bowel Project (NSABP), supported by the National Cancer Institute.

"This innovative, PGRN-enabled international research partnership has produced the first gene-based method to identify which women are likely to benefit from a readily available preventive therapy," said PGRN director Rochelle Long, Ph.D., of the NIH's National Institute of General Medical Sciences. "Because the disease affects so many women worldwide, this work will have a significant impact."

The research, which shows nearly a six-fold difference in disease risk depending on a woman's genetic makeup, appears in the June 13, 2013, issue of Cancer Discovery.

Women undergoing breast cancer preventive treatment take tamoxifen or raloxifene for five years. In rare cases, the drugs can cause dangerous side effects, including blood clots, strokes and endometrial cancer.

Many women never try the therapy because the chance of success seems small (about 50 women in the NSABP trials needed to be treated to prevent one case of breast cancer) compared to the perceived risk of side effects. More women might benefit from the potentially life-saving strategy if doctors could better predict whether the therapy was highly likely to work. That's what the current study begins to do.

The investigators leveraged data from past NSABP breast cancer prevention trials that involved a total of more than 33,000 high-risk women -- the largest sets of such data in the world. Women in the trials gave scientists permission to use their genomic and other information for research purposes.

The scientists 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.

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

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