Androgen receptor-positive triple-negative breast cancer

Androgen receptor is scored by nuclear immunohistochemistry; the trials used more than 10 percent of nuclei as positive, and the enzalutamide trial also enrolled any staining above 0 percent. Of 424 patients with ER- and PR-negative advanced breast cancer screened centrally, 12 percent were AR-positive by the 10 percent rule; bicalutamide 150 mg daily gave a six-month clinical benefit rate of 19 percent (complete or partial response or stable disease over six months) and median progression-free survival of 12 weeks, with no grade 4 or 5 treatment-related events (Gucalp 2013). Enzalutamide 160 mg daily in 118 patients with locally advanced or metastatic AR-positive triple-negative disease gave a 16-week clinical benefit rate of 25 percent overall and 33 percent in the 78 evaluable patients with 10 percent or more nuclear staining, median progression-free survival of 2.9 and 3.3 months and median overall survival of 12.7 and 17.6 months; fatigue was the only treatment-related grade 3 or higher event above 2 percent (Traina 2018). AR expression defines the luminal androgen receptor subtype of Lehmann and Burstein and the molecular apocrine group, whose cells were uniquely sensitive to bicalutamide in the laboratory (Lehmann 2011); LAR tumours are less proliferative and less chemosensitive (29 percent pathological complete response against 41 percent for basal-like 1, Lehmann 2016). Neither antiandrogen is approved for breast cancer; the luminal androgen receptor subtype page sets out the biology and the trials with PI3K-pathway inhibitors.