Genetic biomarkers could help tailor breast cancer therapies

Two gene variants newly identified by researchers may be able to predict which women predisposed to breast cancer could benefit from a certain therapy that can drastically reduce the risk of developing the disease.

The findings, which appeared in the June 13 issue of Cancer Discovery, could help doctors tailor individual treatments for women based on family history of breast cancer and personal medical history, as well as age. The research shows nearly a 6-fold difference in disease risk depending on a woman's genetic makeup. 

"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 lead scientist of the study, Dr. James N. Ingle, professor of oncology at the Mayo Clinic in Rochester, MN, in a statement.

Tamoxifen or raloxifene are common preventive treatments for women prone to breast cancer. Administered for 5 years, the drugs can, in rare cases, cause dangerous side effects including blood clots, strokes and endometrial cancer. The side effects, coupled with the small chance of success, mean that many women never try the therapy, and a biomarker might be able to determine which patients could benefit most from the treatment.

The scientists analyzed genomic data from 33,000 high-risk women and scanned more than 500,000 genetic markers called single nucleotide polymorphisms, or SNPs--which represent a single variation in the DNA sequence at a specific location within the genome--to determine whether any were associated with breast cancer risk.

The study revealed that two markers, one in the gene ZNF423 and the other near a gene called CTSO--act by affecting the activity of BRCA1, a known breast cancer risk gene. Women with the beneficial version of these two markers were 5.71 times less likely to develop breast cancer while taking preventive drugs than were women who didn't have the advantageous SNP. Healthy versions of BRCA1 cut down the chance of disease by repairing a serious form of genetic damage while harmful versions of the gene severely increase a woman's chance of developing breast cancer.

- here's the press release

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