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Original Investigation
February 4, 2021

Efficacy of Endocrine Therapy for the Treatment of Breast Cancer in Men: Results from the MALE Phase 2 Randomized Clinical Trial

Author Affiliations
  • 1Breast Unit, Kliniken Essen-Mitte, Essen, Germany
  • 2German Breast Group, GBG Forschungs GmbH Neu-Isenburg, Germany
  • 3Klinikum St. Marien, Amberg, Germany
  • 4MVZ Kinderwunschzentrum Münster, Germany
  • 5Elisabeth Krankenhaus Kassel, Germany
  • 6Rems-Murr-Klinik-Winnenden, Germany
  • 7SRH Wald-Klinikum, Gera, Germany
  • 8Amedes MVZ Wagnerstibbe für Laboratoriumsmedizin, medizinische Mikrobiologie und Immunologie, Göttingen, Germany
  • 9Endokrinologikum Berlin, Germany
  • 10Department of Medicine II, Hematology and Oncology, Goethe University of Frankfurt, Germany
  • 11Universitätsfrauenklinik Rostock, Germany
  • 12Department of Pathology, Charité – Universitätsmedizin Berlin, Germany
  • 13Universitätsfrauenklinik Aachen, Germany
  • 14Universitätsfrauenklinik Mannheim, Germany
  • 15Universitätsfrauenklinik Ulm, Germany
  • 16Universitätsklinikum Mainz, Germany
  • 17Evangelisches Krankenhaus Bergisch Gladbach, Germany
  • 18Helios-Kliniken Berlin-Buch, Berlin, Germany
  • 19Centre for Haematology and Oncology Bethanien, Frankfurt/Main, Germany
JAMA Oncol. 2021;7(4):565-572. doi:10.1001/jamaoncol.2020.7442
Key Points

Question  How do estradiol levels in male patients with hormone receptor–positive breast cancer change after 3 months of therapy with aromatase inhibitor (AI) plus gonadotropin-releasing hormone analogue (GnRHa) compared with GnRHa plus tamoxifen or tamoxifen alone?

Findings  A total of 52 patients were evaluable in this multicenter, phase 2 randomized clinical trial. There was a profound decrease of estradiol levels in patients receiving tamoxifen plus GnRHa (−85%) vs AI plus GnRHa (−72%), and an increase of estradiol in patients receiving tamoxifen alone (+67%).

Meaning  The combination of AI or tamoxifen with GnRHa significantly decreases the estradiol levels in male patients in contrast to tamoxifen alone after 3 months of therapy.

Abstract

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

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