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New Study Identifies Gene Signature to Predict Outcome for Triple Negative Breast Cancer Patients

Using previously collected samples from other clinical studies, researchers were able to develop a new way to determine prognosis for TNBC patients

Most clinical studies collect blood, tumor samples, or other tissue from participants. While this data is important for the study at hand, the samples may help future studies as well. By storing and later using these collected samples, researchers eliminate the time-consuming and costly process of starting a project from scratch.

This process was key for a recent study published in the Annals of Oncology. A group of investigators used previously collected samples and data from 284 triple negative breast cancer patients from five different trials to develop a test to predict, at the time the patient was diagnosed, an accurate prognosis.

To do so, researchers identified patients that had gene-expression data before treatment and tumor tissue after treatment to assess tumor-infiltrating lymphocytes (TILs). TILs are immune cells that have infiltrated a tumor and indicate an immune response. The authors had previously shown that after neoadjuvant chemotherapy the presence of TILs are associated with more favorable outcomes. The group then wanted to develop a test that could be used at diagnosis to predict if there would be TILs after treatment and therefore indicate a more favorable outcome. They found four genes whose expression correlated to the presence of TILs after treatment and distant relapse-free survival.

This simple four-gene signature could be used in a variety of ways. One possibility is to use the gene-signature to predict which patients are at high risk for relapse when treated with neoadjuvant chemotherapy, and would therefore require additional therapies. Another possibility is to better understand the 4 genes in this test. Some of them may be targetable to improve outcomes or augment immunotherapies.

“The story has a follow up that is incredible,” said Dr. Fabrice André. “One of the four genes is actually a major target to explain immune surveillance through the attraction of macrophages that further suppress T cell responses. The data is incredible. This wouldn’t have been possible without the availability of and access to already collected patient samples.”

Although not funded by BCRF, several other BCRF investigators were also involved in the study, including Drs. Fraser Symmans and Christos Sotiriou. BCRF is funding several other studies to enable this type of research. AURORA US and EU are large multi-institutional trials that will collect blood, tissue, and clinical data that can be made available to other researchers. The MBC Project, led by Dr. Nikhil Wagle, recently publicly released de-identified molecular data for analysis. Other studies are ongoing that will create new models of breast cancer or share resources to accelerate research.

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