What is your experience with directing treatment towards the androgen receptor in metastatic triple negative breast cancer?

There are increasing pre-clinical and clinical data of the potential role for targeting the androgen receptor (AR) in patients with metastatic triple negative breast cancer (TNBC) which express AR. Investigated agents include bicalutamide (Gulap et al CCR 2013) and abiraterone (Bonnefoi et al Ann Oncol 2016): both in tumors with AR >10% by immunohistochemistry. In a recently reported international trial with enzalutamide with tumors with AR >1% (> 55% had AR >10% in evaluable samples), ~ 33% achieved a clinical benefit rate at 16 weeks in evaluable subgroup (primary endpoint): Traina et al JCO 2018. Response rates were < 10%, primarily partial responses. Slightly > 50% were treated in the first or second line.

Clinically, I will check AR ...

Targeting AR has a clinical benefit in appropriately selected patients with TNBC, but there are also a number of challenges in this space. For example, there is significant variability in the reported frequency (7% to 75%) and prognostic significance of AR expression in TNBC (Rampurwala et al. Clin Adv Hematol Oncol 14:186-193, 2016). Moreover, data from large phase 3 trials is lacking. For example the phase III ENDEAR trial (NCT02929576) of paclitaxel plus enzalutamide versus placebo or enzalutamide monotherapy followed by paclitaxel for diagnostic signature-positive TNBC has been withdrawn. However, new agents are in development for AR-positive metastatic breast cancer (TNBC or hormone receptor positive) and include orteronel (TAK-700), a...