Mattea Reinisch1, Sabine Seiler2, Tanja Hauzenberger3, Axel Kamischke4, Sabine Schmatloch5, Hans-Joachim Strittmatter6, Dirk-Michael Zahm7, Christian Thode8, Jenny Furlanetto2, Dominika Strik9, Volker Möbus10, Toralf Reimer11, Bruno Valentin Sinn12, Elmar Stickeler13, Frederik Marmé14, Wolfgang Janni15, Marcus Schmidt16, Christian Rudlowski17, Michael Untch18, Valentina Nekljudova2, Sibylle Loibl2,19. 1. Breast Unit, Kliniken Essen-Mitte, Essen, Germany. 2. German Breast Group, GBG Forschungs GmbH Neu-Isenburg, Germany. 3. Klinikum St. Marien, Amberg, Germany. 4. MVZ Kinderwunschzentrum Münster, Germany. 5. Elisabeth Krankenhaus Kassel, Germany. 6. Rems-Murr-Klinik-Winnenden, Germany. 7. SRH Wald-Klinikum, Gera, Germany. 8. Amedes MVZ Wagnerstibbe für Laboratoriumsmedizin, medizinische Mikrobiologie und Immunologie, Göttingen, Germany. 9. Endokrinologikum Berlin, Germany. 10. Department of Medicine II, Hematology and Oncology, Goethe University of Frankfurt, Germany. 11. Universitätsfrauenklinik Rostock, Germany. 12. Department of Pathology, Charité - Universitätsmedizin Berlin, Germany. 13. Universitätsfrauenklinik Aachen, Germany. 14. Universitätsfrauenklinik Mannheim, Germany. 15. Universitätsfrauenklinik Ulm, Germany. 16. Universitätsklinikum Mainz, Germany. 17. Evangelisches Krankenhaus Bergisch Gladbach, Germany. 18. Helios-Kliniken Berlin-Buch, Berlin, Germany. 19. Centre for Haematology and Oncology Bethanien, Frankfurt/Main, Germany.
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.
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.
Authors: Nina Ditsch; Achim Wöcke; Michael Untch; Christian Jackisch; Ute-Susann Albert; Maggie Banys-Paluchowski; Ingo Bauerfeind; Jens-Uwe Blohmer; Wilfried Budach; Peter Dall; Eva Maria Fallenberg; Peter A Fasching; Tanja N Fehm; Michael Friedrich; Bernd Gerber; Oleg Gluz; Nadia Harbeck; Jörg Heil; Jens Huober; Hans H Kreipe; David Krug; Thorsten Kühn; Sherko Kümmel; Cornelia Kolberg-Liedtke; Sibylle Loibl; Diana Lüftner; Michael Patrick Lux; Nicolai Maass; Christoph Mundhenke; Ulrike Nitz; Tjoung-Won Park-Simon; Toralf Reimer; Kerstin Rhiem; Achim Rody; Marcus Schmidt; Andreas Schneeweiss; Florian Schütz; Hans-Peter Sinn; Christine Solbach; Erich-Franz Solomayer; Elmar Stickeler; Christoph Thomssen; Isabell Witzel; Volkmar Müller; Wolfgang Janni; Marc Thill Journal: Breast Care (Basel) Date: 2022-05-05 Impact factor: 2.268