Adding testosterone to tamoxifen in metastatic male breast cancer: the prospective, single-arm T&T pilot trial

Background Male breast cancer (BC) is very rare and has worse outcomes compared with female BC. Well-tolerated endocrine treatment is an unmet need in this commonly estrogen receptor (ER)- and androgen receptor (AR)-positive disease. Adding testosterone to tamoxifen may improve both tolerability and tumor response in male BC. In this study, we assessed the safety profile and response duration of tamoxifen plus testosterone in patients with metastatic male BC. Patients and methods In this single-center, prospective, single-arm pilot study (NCT05156606), tamoxifen-pretreated male patients with metastatic ER-positive, AR-positive, human epidermal growth factor-2 receptor–negative BC received 20 mg tamoxifen plus 25 mg transdermal testosterone once a day, in addition to gonadal suppression. The primary endpoint was safety [assessed as grade 3-4 adverse events (AEs) according to Common Terminology Criteria for Adverse Events v5.0]. Exploratory endpoints were tumor response and response duration according to RECIST 1.1. Results Five patients were enrolled, in whom mild toxicity was observed: no grade 3-4 AEs and 19 grade 1-2 AEs, two of which were possibly treatment-related (anxiety and nausea). Regarding responses, three of five patients showed clinical benefit with progression-free survival of 24, 21, and 10 months; two of five patients had progressive disease at 8 weeks. All patients spontaneously reported improved well-being. Conclusions In this unique male BC–specific intervention trial, tamoxifen plus testosterone showed good safety and tolerability. These exploratory findings may support future studies with testosterone in male BC to potentially improve compliance and efficacy of endocrine treatment in this rare disease.