Mayo Clinic Finds Genes Associated with Triple-Negative Breast Cancer

Mayo_Editorial_Ken Wolter

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Researchers at the Mayo Clinic, led by geneticist Fergus Couch, identified specific genes associated with triple-negative breast cancer. Triple-negative breast cancer is generally difficult to treat and has a lower five-year survival rate than other types of breast cancer.

Triple-negative breast cancer is called that not because it’s three times as bad—although it is a very aggressive form of cancer. It is called triple-negative because the breast cancer cells test negative for estrogen receptors (ER-), progesterone receptors (PR-) and HER2 (HER2-). The results of being negative for all three means that the cancer growth is not supported by the hormones estrogen and progesterone or by the presence of too many HER2 receptors. As a result, the cancer doesn’t respond to hormonal therapy, like tamoxifen or aromatase inhibitors, or medications that target HER2 receptors, like Herceptin (trastuzumab).

Couch and his team conducted genetic tests on 10,901 patients with triple-negative breast cancer from two studies. They looked for 21 cancer predisposition genes in 8,753 patients and 17 genes in the remaining 2,148 patients. They discovered mutations in BARD1, BRCA1, BRCA2, PALB2 and RAD51D genes. These are associated with a high risk for triple-negative breast cancer and a higher than 20 percent lifetime overall risk of breast cancer in Caucasians. The trend was similar in African-Americans.

The team also found that mutations in the BRIP1 and RAD51C genes were associated with a more moderate risk of triple-negative breast cancer.

Triple-negative breast cancer is seen in about 15 percent of breast cancer patients in the Caucasian population and about 35 percent of breast cancers in the African-American population.

“This study is the first to establish which genes are associated with high lifetime risks of triple-negative breast cancer,” Couch said in a statement. “While previous studies have found genetic variants in BARD1, BRIP1, PALB2 and RAD51C triple-negative breast cancer patients, the current study shows this in more detail, and identifies new specific and strong associations between the susceptibility genes RAD51D and BARD1, and triple-negative breast cancer risk.”

At this time, the findings could potentially lead to better prevention strategies through broader breast cancer screenings. Couch suggests the findings might result in revisions to the National Comprehensive Cancer Network screening guidelines.

NBC News interviewed Sandra Swain, a cancer and genomes researcher at Georgetown University Medical Center, who believes the study results are significant. She was not part of the study. “Triple-negative is hard to treat and has low survival rates, especially in a recurrence,” she said. “It’s really exciting discovering more and more genes that can help with treatment.”

Currently, Swain notes, aside from women or men diagnosed with triple-negative breast cancer, it’s not clear who should be screened for the genetic mutations. More than 30 percent of the patients in the study with triple-negative diagnoses had no family history of breast cancer. Swain points out that other risk factors aren’t well understood. “Unless we start testing everyone for these genes, it’s unclear how we can effectively screen for first-time cases,” she said.

Couch told NBC News, “Some of these genes showed up on genetic panels, and doctors didn’t know what to do with them. Now, they won’t be ignored, and patients will benefit.”

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