Identifying Active Pathways in Triple Negative Breast Cancers Could Lead to More Effective Therapies

Identifying Active Pathways in Triple Negative Breast Cancers Could Lead to More Effective Therapies

Determining gene expression patterns in triple negative breast cancer (TNBC) patients could identify the most effective treatment options for each patient, leading to more targeted, personalized care, according to a new study.

The study, “Effective personalized therapy for breast cancer based on predictions of cell signaling pathway activation from gene expression analysis,” appeared in the scientific journal Oncogene.

“Breast cancer has numerous subtypes,” Eran Andrechek, a physiology professor at Michigan State University (MSU), said in a news release. “Treatments for these various subtypes have to be different because there are different genes that drive the cancer.”

While tumors that are driven by estrogen, progesterone or the tumor-promoting protein HER2 may be treated with hormone therapy or HER2-targeted therapy, TNBCs are more difficult to treat. In fact, only 22 percent of TNBC patients completely respond to chemotherapy, and are far less likely to survive three years after surgery than patients with other breast cancer subtypes.

Looking at the genetic characteristics of TNBC tumors collected from breast cancer animal models, researchers at MSU’s College of Human Medicine found that these tumors had unique genetic patterns related to the activation of certain signaling pathways.

The team then compared the genetic information with drugs that could be used to target the activated pathways.

“Triple-negative breast cancer is highly aggressive and currently there are limited treatment options,” said Andrechek. “By looking at the particular gene expression patterns of this cancer and determining the pathways that were activated, or turned on, we identified certain drugs that could turn these pathways off and stop tumor growth.”

Andrechek’s team found that a three-drug combination targeting a specific pathway associated with TNBC effectively halted tumor growth. The combo included two drugs approved by the U.S. Food and Drug Administration: Gilotrif (afatinib), approved for a subset of lung cancer patients, and Mekinist (trametinib), approved for metastatic melanoma patients.

“We tested several other drug combinations too, and when we expanded our study to include human breast cancers that were grown in mice, we received the same positive result,” Andrechek said. “This gives us a much clearer indication that targeted, individualized breast cancer treatment is viable.”

Overall, these results are a proof-of-concept that a signaling pathway signature-guided treatment is a possible therapeutic approach for TNBC. Researchers also suggest that their approach should be combined with a comprehensive analysis of alterations in individual tumors, which could better inform treatment decisions.

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