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Vanderbilt study finds diverse genetic alterations in triple-negative breast cancers

Dagny Stuart
Most triple-negative breast cancer patients who were treated with chemotherapy to shrink the tumor prior to surgery still had multiple genetic mutations in their tumor cells, according to a study by Vanderbilt-Ingram Cancer Center (VICC) investigators.

Finding multiple mutations instead of just one primary mutation that can be targeted for therapy sheds more light on the challenges of treating triple-negative breast cancer.

The study, led by Justin Balko, Pharm.D., Ph.D., and research faculty in the laboratory of Carlos Arteaga, M.D., director of the Breast Cancer Program at VICC, was presented at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium, held Dec. 4-8.

Approximately 15 percent of breast cancer patients in the U.S. have triple-negative cancer ? a form of the disease that disproportionately affects young African-American women. Triple-negative breast cancer has traditionally been more difficult to treat than other forms of the disease.

?The standard of care for many patients with triple-negative breast cancer is to administer chemotherapy before surgery to shrink the tumor,? Balko said. ?Unfortunately, about 70 percent of patients still have some residual disease at the time of surgery, despite treatment.?

Balko and colleagues profiled residual tumor tissue from 114 patients with triple-negative breast cancer who had received chemotherapy prior to surgery. Triple-negative breast cancer cells do not have estrogen receptors, progesterone receptors, or large amounts of the HER2/neu protein.

The investigators were able to evaluate DNA from 81 tumors and used deep sequencing to examine 182 oncogenes and tumor suppressors that are known to be altered in human cancers. Instead of finding similar genes affected among the patients, they found a diverse set of genes were altered.

?We already knew that triple-negative breast cancer is driven by a diverse group of genetic alterations,? Balko said. ?So, in one way, we fell further down this rabbit hole, but we also found some things that could be promising therapeutically, such as frequent MYC, MCL1 and JAK2 amplifications as well as mutations in the PI3K pathway.?

The additional genetic alterations found in the study may provide targets for new therapies.



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Vanderbilt study finds diverse genetic alterations in triple-negative breast cancers: Most triple-negative breast cancer patients who were treated with chemotherapy to shrink the tumor prior to surgery still had multiple genetic mutations in their tumor cells, according to a study by Vanderbilt-Ingram Cancer Center (VICC) investigators. Finding multiple mutations instead of just one primary mutation that can be targeted for therapy sheds more light on the challenges of treating triple-negative breast cancer. (More...)