Personalized Breast Cancer Prevention

Breast cancer prevention therapy effectiveness varies according to SNP variations

(RxWiki News) The genetic make-up of a cancer can be critical information for treating the disease. Some medications are designed to zero in on specific genetic defects to treat the cancer. Could this info be used before the cancer forms?

Scientists have discovered that variations on two genes could predict which women would benefit from breast cancer prevention therapy using tamoxifen and Evista (raloxifene).

The genetic variations the scientists worked with are called single nucleotide polymorphisms (SNPs).

Women who had favorable variations in the two SNPs were more likely to respond well to preventive therapy.

Women with less favorable patterns may not respond to these medications and may, in fact, have much higher risks of developing breast cancer, according to the new study.

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This study was led by James N. Ingle, MD, professor of oncology at the Mayo Clinic in Rochester, Minn. Dr. Ingle worked with colleagues at the Mayo Clinic, as well as with researchers with the National Surgical Adjuvant Breast and Bowel Project (NSABP) in Pittsburgh, PA and the RIKEN Center for Genomic Medicine in Tokyo, Japan.

Tamoxifen and raloxifene are in a class of drugs called selective estrogen receptor modulators (SERM).

The US Preventive Services Task Force guidelines suggest that SERM therapy with these two medications can reduce the risk of women developing breast cancer. It’s also known that this approach doesn’t work for everyone.

“The selective estrogen receptor modulators (SERM) tamoxifen and raloxifene can reduce the occurrence of breast cancer in high-risk women by 50 percent, but this US Food and Drug Administration-approved prevention therapy is not often used,” the authors wrote.

Dr. Ingle and team analyzed DNA samples collected from the National Surgical Adjuvant Breast and Bowel Project (NSABP) P-1 trial of tamoxifen and the NSABP P-2 trial that compared raloxifene with tamoxifen. These studies involved more than 33,000 women.

Researchers analyzed the DNA of 592 patients who developed breast cancer while on SERM therapy and 1,171 matched controls.

The first discovery was that two SNPs were key to prevention effectiveness – one on gene ZNF423 and the other on gene CTSO.

The most common variation of these two SNPs helped estrogen drive cancer development. In the less common form of the SNPs, women saw a substantial lowering of breast cancer risk.

In addition to evaluating prevention, the scientists looked at the overall breast cancer risks in both groups.

Women with favorable SNP variations had the lowest risk of developing breast cancer, while women with unfavorable variations in these SNPs had more than a five-fold increased risk of developing breast cancer.

“Our discovery is a major step toward truly individualized prevention of breast cancer. Findings from our study provide clear direction as to which women are likely and which are unlikely to benefit from tamoxifen or raloxifene,” said Ingle. “The best chance we have of decreasing the burden of breast cancer is to prevent it in the first place. Our findings provide the basis for a reinvigoration of research efforts in breast cancer prevention.”

This research was published June 13 in Cancer Discovery, a journal of the American Association for Cancer Research.

The research was funded by grants from the National Institutes of Health, the RIKEN Center for Genomic Medicine and the Biobank Japan Project funded by the Ministry of Education, Culture, Sports, Science, and Technology, Japan.

No potential conflicts of interest were disclosed.

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Review Date: 
June 14, 2013