LAS VEGAS – Despite the early promise of antiandrogen therapy, it’s not time yet to routinely screen women with triple-negative breast cancer for androgen receptors, according to Tiffany A. Traina, MD, the head of research into the disease at Memorial Sloan Kettering Cancer Center, New York.
Dr. Tiffany A.Traina
There’s no standardized test for androgen receptors in breast cancer, so people “are doing different kinds of testing.” In the literature, “the range of AR positivity is anywhere from 12% to 79%, which reflects how we are all over the map in methodology; you might just as well throw a dart at the board. I would encourage screening in the context of the ongoing trials,” Dr. Traina said.
More than a decade ago, Memorial Sloan Kettering found a subset of TNBC that had ARs, which was peculiar because the tumors weren’t otherwise responsive to hormones. Androgen exposure increased growth, but the AR antagonist flutamide (Eulexin)blocked it. “It was thought provoking. There are a lot of drugs in the prostate cancer world” such as flutamide that shut down androgens, she said (Oncogene. 2006 Jun 29;25[28]:3994-4008).
Several have been tried, and investigations are ongoing. The work matters because TNBC is a particularly bad diagnosis. Blocking androgens seems to give some women a few more months of life.
Dr. Traina was the senior author in an early proof-of-concept study for AR blockade that involved 26 women with metastatic TNBC who had been through up to eight prior chemotherapy regimens. The women received 150 mg daily of the prostate cancer AR antagonist bicalutamide (Casodex). Disease remained stable in five (19%) for more than 6 months. Median progression-free survival was 12 weeks, which was “not that far off from what you get with [standard] chemotherapies. This was encouraging, and it led to multiple other trials looking at targeted therapies,” she said (Clin Cancer Res. 2013 Oct 1; 19[19]: 5505-12).
Dr. Traina led a phase II investigation of the prostate cancer AR antagonist enzalutamide (Xtandi) in 118 women with advanced AR-positive TNBC. Her team created an androgen-driven gene signature as a potential biomarker of response. Median progression-free survival was 32 weeks in the 56 women (47%) who were positive for the gene signature, but 9 weeks in those who were not. There were two complete responses and five partial responses with enzalutamide. Currently, “we are looking at using enzalutamide for patients with AR-positive TNBC in the early stage after failure of standard therapies,” she said.
French investigators recently reported a 6-month clinical benefit – including one complete response – in 7 (21%) of 34 women with locally advanced or metastatic TNBC who were treated with 1,000 mg daily of abiraterone acetate (Zytiga), an androgen biosynthesis inhibitor approved for prostate cancer (Ann Oncol. 2016 May;27[5]:812-8).
“We still have a ways to go” before AR treatment reaches the clinic for routine breast cancer treatment, “but there’s reason for hope,” Dr. Traina said.
Dr. Traina reported funding, honoraria, and steering committing payments from a number of companies working on or marketing TNBC AR drugs, including Pfizer, Astellas, Innocrin, AstraZeneca, Eisai, and Merck.