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

JAMA Oncol. 2021 Apr 1;7(4):565-572. doi: 10.1001/jamaoncol.2020.7442.

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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Hormonal / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Aromatase Inhibitors / therapeutic use
  • Breast Neoplasms* / chemically induced
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms, Male* / drug therapy
  • Chemotherapy, Adjuvant
  • Humans
  • Male
  • Middle Aged
  • Quality of Life
  • Tamoxifen / adverse effects

Substances

  • Antineoplastic Agents, Hormonal
  • Aromatase Inhibitors
  • Tamoxifen

Associated data

  • ClinicalTrials.gov/NCT01638247