Triple-negative breast cancer: Even Low-androgen Tumors Respond to Anti-androgen Therapy

What You Need to Know: Only about 1 percent of triple-negative breast cancer cells in a tumor must be “androgen-receptor-positive” to show benefit from anti-androgen therapies. There are no FDA-approved targeted therapies for triple-negative breast cancer. Clinical trials currently underway are showing promising preliminary results of anti-androgen-receptor therapies against triple-negative breast cancers expressing a higher percentage of androgen-receptor-positive cells.

Background: Triple-negative breast cancers are those without known hormone or genetic drivers — specifically, breast cancers that do not drive their growth with the hormones estrogen or progesterone, or with the gene HER2. Without a known driver, there has been no “target” in triple-negative breast cancer to treat with targeted therapies, and the triple-negative subtype has the worst five-year survival rate of any breast cancer.

“What we’re showing is that the threshold for benefit from anti-androgen-receptor therapies in triple-negative breast cancer may be far lower than we previously thought. This is an extremely optimistic finding for many people who have been without options for targeted cancer therapy,” says Valerie Barton, the study’s first author and PhD candidate in the lab of CU Cancer Center investigator Jennifer Richer, PhD. “We’re getting closer to being able to call some triple-negative breast cancers, androgen-receptor-positive breast cancers. And we may have to start referring to the remaining triple-negative breast cancers that are completely without androgen receptors as quadruple-negative breast cancers,” Barton says.

The current study treated triple-negative breast cancer cells with the anti-androgen-receptor drug Enzalutamide, currently FDA approved for use as an anti-androgen against prostate cancer. It has been previously shown that Enzalutamide is active against “luminal” triple-negative breast cancer cells that tend to have abundant androgen receptors. The researchers tested Enzalutamide against non-luminal triple-negative breast cancer cell lines that have far fewer androgen receptors.

“Even in these cells and in mouse models of tumors with low percentage of androgen receptor positive breast cancer cells, we observed that Enzalutamide was significantly effective at reducing proliferation, growth, migration and invasion of cancer cells,” Barton says.

My Take: These results suggest that anti-androgen receptor therapy may benefit a larger percentage of triple negative breast cancers than previously thought. We look forward to results from human clinical trials. I’m Dr. Michael Hunter.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

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Journal References:

  1.  Valerie N. Barton, Nicholas C. D’amato, Michael A. Gordon, Hanne T. Lind, Nicole S. Spoelstra, Beatrice L. Babbs, Richard E. Heinz, Anthony Elias, Paul Jedlicka, Britta M. Jacobsen, and Jennifer K. Richer. Multiple Molecular Subtypes of Triple-Negative Breast Cancer Critically Rely on Androgen Receptor and Respond to Enzalutamide In Vivo. Molecular Cancer Therapeutics, February 2015 DOI: 10.1158/1535-7163.MCT-14-0926
  2. University of Colorado Cancer Center. “In triple-negative breast cancer, even low-androgen tumors respond to anti-androgen therapy.” ScienceDaily. ScienceDaily, 24 February 2015. <www.sciencedaily.com/releases/2015/02/150224131201.htm>.

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understandcancerin60minutes

Harvard AB Yale MD UPenn Radiation Oncology Radiation Oncologist, Seattle area

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