A University of Colorado Cancer Center study shows that androgen receptor (AR) may play a role in triple negative breast cancer (TNBC) metastasis.

“TNBC accounts for approximately 15 to 20 percent of newly diagnosed breast cancers, is the most clinically aggressive and metastasizes more quickly than other subtypes of breast cancer,” explains Jessica Christenson, PhD, investigator at the CU Cancer Center and Post-Doctoral Fellow in JenniferRicher’s laboratory. “These tumors are also especially difficult to treat since, as their name implies, they do not express the most common breast cancer molecular markers, the estrogen receptor (ER), progesterone receptor (PR) or the growth factor HER2, that normally serve as therapeutic targets. Studies have shown that up to 50 percent of TNBCs express AR; however little has been done to understand how the receptor affects breast cancer metastasis to distant organs such as the lung.”

Christenson characterized AR expression in an immunocompetent animal model of breast cancer in order to learn more about TNBC primary tumor growth and metastasis. She found that late-stage primary tumors and metastases, as well as Met-1 cells (derived from a late-stage primary tumor), expressed high levels of AR. When she treated the primary tumors with an anti-androgen, the second-generation AR-inhibitor enzalutamide, she found those tumors rely on AR for growth and are responsive to anti-androgen therapy.

Her data also suggests that AR may play a role in tumor progression from the primary site, specifically to the lungs.

“Certain lung cells normally express AR. When the lung is damaged a set of events are set into motion to heal that injury, known as wound healing. During wound healing the lung cells that express AR multiply to try to fill in and repair the wound,” explains Christenson. “I think that the reason we see more AR+ lung cells surrounding lung metastases is a result of the lung trying to heal a ‘wound’ that is actually a metastasis. Wound healing, which is normally a good thing, may actually be contributing to the survival and growth of metastases.” The breast cancers seem to have co-opted this process to help them survive in the lung metastatic niche.

“My hope in the future is that these experiments and the knowledge gained through this research will provide the foundation for the development of metastasis-specific drugs, such as anti-androgens, that can be directly administered to the lung,” she says. This strategy could potentially reduce mortality from metastatic breast cancer to the lung and improve the quality of life for patients living with metastatic disease.