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A recap of triple-negative breast cancer research from San Antonio

BY GUEST
PUBLISHED SUNDAY, DECEMBER 9, 2012
The best news from the 2012 San Antonio Breast Cancer Symposium is its emphasis on triple-negative breast cancer. There are so many papers presented on the subject that I can't keep up. Those of us who have been hanging around this dance for a long time--I was diagnosed in 2006--remember the frustration of seeing and hearing little about this disease from researchers and nothing from the media, who simply didn't appear to comprehend the complexity of breast cancer as a whole and were unaware that there was a type not fueled by estrogen or progesterone. And HER2? What's that?

That is changing. More than 82 clinical trials are now looking for targeted treatments for TNBC. Because TNBC is defined by what it lacks--receptors for estrogen, progesterone and HER2/neu--it also lacks a targeted therapy. Researchers are busy finding a genetic signature of subsets of TNBC that will lead to those therapies.

The San Antonio symposium this year had at least 20 papers looking at the genetics of TNBC, its response to chemo, and the potential for those targeted drugs, which no longer look as elusive as they had once been.

The highlights of research presented on TNBC this year:

Androgens

Some 75 percent of all breast cancers and 10 to 20 percent of triple negative cancers are positive for the androgen receptor. Several research studies have looked at the influence of androgen receptors on TNBC, which means new treatments plus a broader and deeper understanding of the disease. TNBC cancers that are also positive for androgen receptors are molecularly similar to prostate cancer and could potentially be treated similarly.

AR-positive tumors responded well to bicalutamine and to 17-DMAG, a drug that has been recently in clinical trials, according to research presented by Jennifer Pietenpol, PhD, director of the Vanderbilt-Ingram Cancer Center.

A phase 1 clinical trial at the University of Colorado has been studying the effectiveness of enzalutamide, a drug used to treat prostate cancer, on triple-negative. A phase 2 trial is planned at Colorado, Memorial Sloan-Kettering Cancer Center and the Karmanos Cancer Institute.

A Heterogeneous Disease

It is increasingly clear that TNBC is not one disease, but a family of diseases, some of which are highly aggressive, and some that are not aggressive at all. We're getting increasingly closer to knowing which ones are which.

"This heterogeniety highlights the need for personal medicine," said Justin M. Balko, PharmD, PhD, research faculty in the laboratory of Carlos Arteaga, MD, at the Vanderbilt-Ingram Cancer Center in Nashville, Tenn. Balko's research looked at how TNBC tumors changed genetically after neoadjuvant chemotherapy, and highlighted frequent mutations and amplifications, including the novel JAK2 genetic mutation, that can lead future research and the development of TNBC-specific drugs.

The JAK2 gene has not been observed in previous research, Balko said. 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.

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