LAUSR

Importance The extent of changes in estradiol levels in male patients with hormone receptor-positive breast cancer receiving standard endocrine therapies is unknown. The sexual function and quality of life related to those changes have not been adequately evaluated. Objective To assess the changes in estradiol levels in male patients with breast cancer after 3 months of therapy. Design, Setting, and Participants This multicenter, phase 2 randomized clinical trial assessed 56 male patients with hormone receptor-positive breast cancer. Patients were recruited from 24 breast units across Germany between October 2012 and May 2017. The last patient completed 6 months of treatment in December 2017. The analysis data set was locked on August 24, 2018, and analysis was completed on December 19, 2018. Interventions Patients were randomized to 1 of 3 arms: tamoxifen alone or tamoxifen plus gonadotropin-releasing hormone analogue (GnRHa) or aromatase inhibitor (AI) plus GnRHa for 6 months. Main Outcomes and Measures The primary end point was the change in estradiol levels from baseline to 3 months. Secondary end points were changes of estradiol levels after 6 months, changes of additional hormonal parameters, adverse effects, sexual function, and quality of life after 3 and 6 months. Results In this phase 2 randomized clinical trial, a total of 52 of 56 male patients with a median (range) age of 61.5 (37-83) years started treatment. A total of 3 patients discontinued study treatment prematurely, 1 in each arm. A total of 50 patients were evaluable for the primary end point. After 3 months the patients' median estradiol levels increased by 67% (a change of +17.0 ng/L) with tamoxifen, decreased by 85% (-23.0 ng/L) with tamoxifen plus GnRHa, and decreased by 72% (-18.5 ng/L) with AI plus GnRHa (P < .001). After 6 months, median estradiol levels increased by 41% (a change of +12 ng/L) with tamoxifen, decreased by 61% (-19.5 ng/L) with tamoxifen plus GnRHa, and decreased by 64% (-17.0 ng/L) with AI plus GnRHa (P < .001). Sexual function and quality of life decreased when GnRHa was added but were unchanged with tamoxifen alone. Conclusions and Relevance This phase 2 randomized clinical trial found that AI or tamoxifen plus GnRHa vs tamoxifen alone led to a sustained decrease of estradiol levels. The decreased hormonal parameters were associated with impaired sexual function and quality of life. Trial Registration ClinicalTrials.gov Identifier: NCT01638247.