Test Predicts Harmful Breast Cancer Mutations

A multiple gene expression-profile test is able to predict the presence of harmful breast cancer type 1 (BRCA1) or BRCA2 gene mutations in otherwise healthy women carrying the mutation.

Women with a mutation in their BRCA1 or BRCA2 gene have a significantly increased risk for developing breast cancer or ovarian cancer, and for many of those at risk the disease may develop at an early age.

Scientists at the Hadassah Hebrew University Medical Center (Jerusalem, Israel) obtained fresh blood samples from proven BRCA1 or BRCA2 mutation carriers and mutation-negative women. All subjects were healthy women between ages 25 and 50 years, with no personal history of cancer. The test was carried out on leucocytes from the blood samples donated by nine healthy women with a mutated BRCA1 gene and eight healthy women with a mutated BRCA2 gene. The investigators extracted the total ribonucleic acid (RNA) from these cells and compared it to the total RNA from identically treated white blood cells from 10 healthy, noncarrier women.

About 1,500 genes were differentially expressed between carriers and noncarriers. The list was narrowed down to 18 genes that were the most significantly differentiated between the two groups of women. The final narrowing was done with a validation study of a model using 21 of the newly identified genes and five control genes to predict the risk for carrying a mutation. The blood samples used were from an independent group of 40 women who were carriers of mutated BRCA1 and/or BRCA2 and 17 noncarrier women. The model had a sensitivity of 95% and a specificity of 88%.


Asher Y. Salmon, MD, the senior author and a breast cancer specialist, said, "In wealthy societies, it can become a screening tool for identifying individuals with a very high susceptibility for carrying a mutation, and full sequencing can be reserved only for them. In societies in which sequencing is not feasible, this test can substitute for it with a very high accuracy rate." The study was published on January 22, 2013, in the journal Cancer Prevention Research.

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Hadassah Hebrew University Medical Center