Justin M. Balko, PharmD, PhD, a research faculty member who works in the lab of Carlos Arteaga, MD, at the Vanderbilt-Ingram Cancer Center in Nashville, Tennessee, describes a study that discovered JAK2 alterations in patients with treatment-refractory triple-negative breast cancer (TNBC).

In the study, 81 tumor samples were interrogated for the presence of multiple tumor suppressor and oncogenes in patients with treatment-refractory residual TNBC following neoadjuvant chemotherapy. In addition to other findings, the trial discovered that approximately 10% of patients had a copy number alteration in JAK2.

A confirmatory analysis of these findings is still needed but other indicators support their authenticity. For instance, Balko notes, the analysis found increased levels of the cytokine interleukin 6, which is known to activate the JAK-STAT pathway. Additionally, the rapidity of recurrence following treatment may be consistent with the connection between the JAK-STAT pathway and stem cell activity.

These findings are particularly encouraging, since JAK2 inhibitors are currently in clinical trials and FDA approved. Larger randomized trials investigating a JAK2 inhibitor in TNBC still need to be undertaken, Balko believes.

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Justin M. Balko, PharmD, PhD, from the Vanderbilt-Ingram Cancer Center, describes a study that discovered JAK2 alterations in patients with treatment-refractory triple-negative breast cancer.

Justin Balko on JAK2 Amplification in TNBC

Justin M. Balko, PharmD, PhD, a research faculty member who works in the lab of Carlos Arteaga, MD, at the Vanderbilt-Ingram Cancer Center in Nashville, Tennessee, discusses research into clinically targetable genetic alterations in patients with triple-negative breast cancer (TNBC).

In the study, 81 tumor samples were examined for a panel of 182 tumor suppressor genes and oncogenes, using next-generation sequencing techniques. The trial found a wide range in the number of mutations in each TNBC sample. Some tumors were found to harbor up to 7 different alterations and a majority had at least 1 mutation in 

, which occurred in approximately 95% of samples.

Given the broad diversity of mutations found in TNBC, the best approach may be to organize these alterations into pathways, believes Balko. Many of the alterations resided in targetable clinical pathway, including PI3k/mTOR, cell cycle, DNA repair, and Ras/MAPK. Using a single pathway inhibitor may be the best approach for future trials in TNBC, Balko notes.

Justin M. Balko, PharmD, PhD, from the Vanderbilt-Ingram Cancer Center, discusses research into clinically targetable genetic alterations in patients with triple-negative breast cancer.

Justin M. Balko, PharmD, PhD

Articles

Justin Balko on JAK2 Amplification in TNBC

Justin Balko on the Diversity of Genetic Alterations in TNBC