Thursday, December 6, 2012

SABCS: JAK2, other genes, show need for personalized TNBC treatment

Diverse Genetic Alterations After Neoadjuvant Chemotherapy

Roughly 30 percent of triple-negative breast cancers have a complete pathological response after neoadjuvant chemotherapy, which leads to an extremely rosy prognosis.  But nearly 70 percent have residual cancer cells that have the potential to lead to a recurrence.  Right now, there is no targeted therapy for TNBC patients with an incomplete pathological response other than watching and waiting.  

By determining the genetic makeup of the cancer cells remaining after neoadjuvant (NAD) chemotherapy, researchers hope to ultimately find that targeted therapy that will reduce the risk of recurrence of TNBC.

Put another way, this can be another means of defining what drives TNBC—and how to stop its journey through our bodies.  

Researchers presenting today at the 35th annual San Antonio Breast Cancer Symposium.studied tumors from 114 clinically-defined TNBC patients with residual disease after NAC and found:

• Frequent mutations in the PI3K pathway (90 percent)
• Frequent amplifications of MYC (33 percent), MCL1 (56 percent) and JAK2 (11 percent)

The JAK2 gene has not been observed in previous research, according to lead author
Justin M. Balko, Pharm.D, Ph.D., research faculty who led this study in the laboratory of Carlos Arteaga, M.D., at the Vanderbilt-Ingram Cancer Center in Nashville, Tennessee.

The patients in the study who had the JAK2 amplification tended to have a poor prognosis, which means that JAK2 may be a key to which cases of TNBC are aggressive and which aren’t.  Those with JAK2 expression may respond to inhibitors currently in clinical trials for inflammatory diseases, Balko said, which could be a game changer.  

Others could respond to p13K/m/TOR inhibitors; DNA-repair targeting agents; RAF/MEK inhibitors; cell-cycle/mitotic spindle inhibitors; and targeted RTK inhibitors.

"This heterogeniety highlights the need for personal medicine," Balko said.

Read more about TNBC in my book, Surviving Triple-Negative Breast Cancer.

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