Targeted treatments for triple-negative breast cancers--which test negative for estrogen (ER), progesterone (PR), and HER2 receptors--have been nonexistent outside of clinical trials. The problem being, without a hormonal target or genetic driver, drug development for this cancer population is challenging--until now.
A new study published in Molecular Cancer Therapeutics, details the work of researchers at the University of Colorado who made the discovery that only the smallest fraction of triple-negative breast cancer cells in a tumor (1%) must be androgen-receptor-positive to benefit from anti-androgen therapies. This study aims to prove that androgen receptors are drivers and targets in breast cancer.
Triple-negative breast cancer is very aggressive and has the worst 5-year survival rate of all invasive breast carcinomas, so the sooner a therapy becomes available, the better.
This cancer subtype does not respond to existing therapies, such as tamoxifen, aromatase inhibitors, or trastuzumab (Herceptin)—which targets the HER2/neu gene. The US Food and Drug Administration (FDA) has approved enzalutamide (Xtandi), as an anti-androgen therapy for prostate cancer, and is currently being studied in luminal, triple-negative breast tumors that exhibit an abundant amount of androgen receptors.
In ongoing clinical trials, enzalutamide has shown to cause cell death in luminal, triple-negative breast cancer cells, which have many androgen receptors. Researchers also tested enzalutamide in non-luminal, triple-negative breast cancer cell lines that have fewer androgen receptors, and the drug was still effective:
"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," said Valerie Barton, the study's first author, and PhD candidate in the lab of the University of Colorado Cancer Center in Denver.
"Our results suggest that anti-androgen receptor therapy may benefit a larger percentage of triple-negative breast cancers than previously thought," Barton said.
Perhaps in the future, women will be tested for androgen receptors--which previously may have seemed counter intuitive. Also, the way these cancers are described may change as well. The medical community may soon refer to triple-negative breast cancer as "androgen-receptor-positive breast cancer" when androgen receptors are present, and for the remaining without androgen receptors, "quadruple-negative breast cancer" may be more appropriate.