We are delighted to inform you that final results of the first randomized phase II MALE trial have been published in JAMA Oncology.
Breast cancer (BC) in men is rare and the great majority of existing data are case reports or retrospective monocentric studies. Data from large-scale prospective, randomized clinical studies are lacking, the majority of available analysis are lacking sufficient statistical power. Treatment recommendations have been extrapolated from female BC. Therefore, 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. The aim of this study was to assess the changes in estradiol levels in male patients with breast cancer after 3 months of therapy.
In the MALE study, male patients with hormone receptor-positive breast cancer 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. 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.
Between October 2012 and May 2017, 56 male patients with HR-positive BC were randomized within 24 centers in Germany, of which 52 started treatment and were included in the safety set. The median age was 61.5 (range 37-83) years, the majority had T2 (52.9%), G2 (57.7%), HER2-negative (86.5%) and node negative (52.0%) tumor, and included in the adjuvant setting (94.2%). 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. At baseline, median estradiol levels were not significantly different between the three treatment arms: 27.0 (range 5.0- 46.0) ng/L for tamoxifen, 33.0 (14.0- 45.0) ng/L for tamoxifen+ GnRHa, and 27.5 (17.0- 113.0) ng/L for AI+ GnRHa (p=0.28). 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<0.001). 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<0.001). Sexual function and quality of life decreased when GnRHa was added but were unchanged with tamoxifen alone.
In conclusion, MALE is the first randomized study to investigate different endocrine therapy approaches. 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.
Reinisch M, Seiler S, Hauzenberger T, et al. Efficacy of Endocrine Therapy for the Treatment of Breast Cancer in Men: Results from the MALE Phase 2 Randomized Clinical Trial. JAMA Oncol. 2021 Feb 4. doi: 10.1001/jamaoncol.2020.7442.