Role of gonadotropin-releasing hormone analogues in metastatic male breast cancer: results from a pooled analysis.

Isabella Sperduti,Marcella Mottolese,Luigi Di Lauro,Maddalena Barba,Patrizia Vici,Carla Azzurra Amoreo,Ruggero De Maria,Domenico Sergi,Daniele Santini,Franca Belli,Laura Pizzuti,Marcello Maugeri-Saccà,Valerie Speirs

doi:10.1186/s13045-015-0147-z

Abstract

BackgroundMale breast cancer is a rare malignancy. Despite the lack of prospectively generated data from trials in either the adjuvant or metastatic setting, patients are commonly treated with hormone therapies. Much controversy exists over the use of gonadotropin-releasing hormone analogues in metastatic male breast cancer patients. We conducted this study to provide more concrete ground on the use of gonadotropin-releasing hormone analogues in this setting.MethodsWe herein present results from a pooled analysis including 60 metastatic male breast cancer patients treated with either an aromatase inhibitor or cyproterone acetate as a monotherapy (23 patients) or combined with a gonadotropin-releasing hormone analogue (37 patients).ResultsOverall response rate was 43.5 % in patients treated with monotherapy and 51.3 % with combination therapy (p = 0.6). Survival outcomes favored combination therapy in terms of median progression-free survival (11.6 months versus 6 months; p = 0.05), 1-year progression-free survival rate (43.2 % versus 21.7 %; p = 0.05), median overall survival (29.7 months versus 22 months; p = 0.05), and 2-year survival rate (64.9 % versus 43.5 %; p = 0.05).ConclusionsIn metastatic male breast cancer patients, the combined use of gonadotropin-releasing hormone analogues and aromatase inhibitors or antiandrogens seems to be associated with greater efficacy, particularly in terms of survival outcomes, compared with monotherapy. Collectively, these results encourage considering these agents in the metastatic setting.

Highlights

Male breast cancer is a rare malignancy
For Male breast cancer (MBC) patients, implications of increased T levels are twofold: i) the counteraction of the block imposed by aromatase inhibitors (AIs) through an excess of substrate and ii) a direct stimulation of cancer cells equipped with the androgen receptor (AR) [21]
Sixty men mostly treated in the first-line metastatic setting were included in the present analysis

Summary

Introduction

Male breast cancer is a rare malignancy. Despite the lack of prospectively generated data from trials in either the adjuvant or metastatic setting, patients are commonly treated with hormone therapies. Much controversy exists over the use of gonadotropin-releasing hormone analogues in metastatic male breast cancer patients. A heated argument surrounds the question of whether gonadotropin-releasing hormone analogues (GnRH analogues) are worth being administered in combination with other hormonal treatments acting on peripheral targets [7, 8, 13] This controversy was fuelled by the advent of AIs [15]. Our group reported on the antitumor activity of antiandrogens [11, 12], a finding we recently strengthened in a larger series where hints on the existence of an association between AR expression and clinical outcomes were provided [13] In this case, the use of antiandrogens with a GnRH analogue stemmed from the need to neutralize testicular and adrenal androgens, theorizing analogies in terms of androgen dependency between MBC and prostate cancer [13]. These effects were observed, to a lower extent, with CPA monotherapy [11]

Methods

Results

Discussion

Conclusion