SABCS: Genetic Research Adds to Definition of Triple-Negative

We’re getting closer and closer to the point at which the term “triple-negative breast cancer” is old hat.  Based on research presented today at the 35^th San Antonio Breast Cancer Symposium, we’ll soon be adding other receptors to the definition.  And we’ll be looking at a whole set of genetic markers that define how the disease behaves and how it responds to a growing field of cancer drugs.

Triple-negative breast cancer is defined by what it lacks: receptors for estrogen, progesterone, and her2/neu.

Androgen receptors may be added as an essential marker in the disease.   The p53 gene continues to be a major player, as is the pik2ca mutation.  Add this to the fact that many, but not all, TNBC tumors are basal-like and many, but not all, of those are connected to the BRCA genetic mutations, and you get a sense of the complexity of this disease.

“It’s a highly heterogeneous disease,” said Jennifer Pietenpol , Ph.D., director of the Vanderbilt-Ingram Cancer Center.  Pietenpol and her colleagues have identified six named subtypes of triple-negative and one unnamed variant, based on genomic and molecular analyses. Those named subtypes:

•Basal-like 1

•Basal-like 2

• Mesenchymal

• Mesenchymal/stem-like

• Iimmunomodulatory

• Androgen-driven luminal

Each of these responds differently to treatment, but Pietenpol focused most on the two basal-like forms and the androgen (AR)-luminal subtype.

Basal-like cancers are extremely sensitive to cisplatin, she said.  AR-positive tumors also were most likely to have pik3ca mutations and to respond to pik3ca inhibitors plus cisplatin.

“Some of these patients had amazing responses to treatments.  They were pretty dramatic,” she said. 

TNBC cancers that are also positive for androgen receptors are molecularly similar to prostate cancer and could potentially be treated similarly.  In Pietenpol’s  research, AR-positive tumors responded well to bicalutamine and to 17-DMAG, a drug that has been recently in clinical trials.

We’re on the road to targeted therapies for TNBC.  And a whole lot of hope.

 “Genomics are going to be the mainstay of personalized medicine,” said Thomas Westbrook, Ph. D., of the Baylor College of Medicine.

NOTE:  Pietenpol  and her colleagues have developed a web-based subtyping tool for TNBC tumor samples.

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

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