Abstract OT2-2-05: A prospective, randomised multi-centre phase II study evaluating the adjuvant, neoadjuvant or palliative treatment with tamoxifen +/− GnRH analogue versus aromatase inhibitor + GnRH analogue in male breast cancer patients (GBG-54 MALE)
Authors: Linder M , von Minckwitz G , Kamischke A , Rudlowski C , Eggemann H , Nekljudova V , Loibl S 
Published: August 2014

Abstract
Background: Breast cancer (BC) in men is a rare disease accounting for 0.5–1% of all BC. The only available information on endocrine therapies derives from few retrospective case series and studies with small numbers of patients (pts). Treatment strategies are not based on data from prospective, randomised clinical studies and optimal therapy is unknown. Current clinical management is extrapolated from principles established for female BC. As 90% of male pts have hormone receptor positive BC, they receive tamoxifen 20mg as standard adjuvant therapy.
Although women benefit from treatment with aromatase inhibitors (AI), only case reports exist of men treated with AI. Data from other entities show, that AI only suppresses oestradiol of 40–50% with an increase of testosterone. Among men on AIs, the hypothalamic-pituitary feedback loop results in an increase substrate for aromatisation. By adding a gonadotropin-releasing hormone analogue (GnRH), the feedback loop would be interrupted and complete oestrogen suppression may be achieved.
Patients and Methods: The MALE study is a prospective, randomized, phase II study in which 48 male pts will be included in the adjuvant, neoadjuvant and metastatic setting. In a 3-arm design, endocrine therapies are compared consisting of tamoxifen 20mg daily versus tamoxifen daily+GnRH on day 1 and after 3 months versus exemestane 25mg daily+GnRH on day 1 and after 3 months. The treatment duration is 6 months. The primary aim is to determine the oestradiol suppression after 3 months. Secondary endpoints are to compare the oestradiol suppression after 6 months and to assess the compliance (with standardized questionnaires as Aging Male Symptom Score, International Index of Erectile function and International Prostate Symptom Score), safety and toxicity profile. The determination of the predefined hormones at baseline and after 3 and 6 months will be measured centrally. After the antihormonal treatment, all pts should be treated according to local recommendations. Included can be men with primary or metastatic endocrine sensitive BC with an indication of an endocrine therapy who did not receive prior antihormonal therapy; prior chemotherapy is allowed.
16 evaluable pts per group are needed for the Kruskal-Wallis-Test to have 80% power to detect at the 5% significance level a difference. The translational research programme includes the determination of cytochrome P450 polymorphisms, the hormone receptor activity and aromatase expression of the tumour tissue.
Results: The time of recruitment should not exceed 2 years with 36 recruiting sites in Germany. As no study specific treatment or investigation is planned after the end of treatment, surgery and follow up are not part of this study, however information on the health status of the pts will be collected. The trial has been opened in May 2012 and is currently recruiting.
Conclusion: This is the first study randomizing men with BC to investigate the ability to suppress estradiol of different endocrine regimen.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT2-2-05.