Tamoxifen +/- GnRH Analogue vs Aromatase Inhibitor + GnRH Analogue in Male Breast Cancer Patients
Condition: Male Breast Cancer
MeSH terms: Breast Neoplasms; Breast Neoplasms, Male
Study type: Interventional
Phase: Phase 3

Summary: 
      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 (MALE).
    

Detailed description: 
      Breast cancer in men is a rare disease with approximately 0.5- 1% of all breast cancer cases.
      Each year, about 400 to 450 cases are diagnosed in Germany. Men tend to present with more
      advanced disease than women, probably due to the lack of awareness of male breast cancer from
      both, the patient and the physicians.

      Therefore, at presentation they usually have lump or nipple inversion, and more than 40% of
      the patients have a stage III or IV disease. The great majority of patients have an invasive
      ductal (90%), hormone receptor positive (90%), HER2 negative (90%) tumor.

      The only available information on adjuvant therapies derives from few retrospective cases and
      retrospective studies with a little number of cases. Therefore, treatment strategies are not
      based on data from prospective, randomised clinical studies, and optimal treatment is
      unknown. As a result, current clinical management is generally extrapolated from principles
      established for the treatment of female breast carcinoma. As the majority of male breast
      cancer patients have a hormone receptor positive tumor, they receive tamoxifen 20 mg for five
      years as standard endocrine adjuvant therapy. A lot of withdrawals from the treatment were
      documented in male breast cancer due to side-effects under tamoxifen therapy. Furthermore,
      the clinical outcome of tamoxifen-treated male breast cancer patients may be influenced by
      the activity of cytochrome P450 2D6 enzymes that catalyse the formation of anti-estrogenic
      metabolites endoxifen and 4-hydroxy-tamoxifen. Therefore a significant proportion of poor to
      moderate metaboliser is proposed to do not benefit from adjuvant tamoxifen therapy.

      Although women benefit from adjuvant treatment with aromatase inhibitors (AI) regarding
      disease-free-survival, overall survival and treatment toxicity, only case reports of men
      treated with AI exist. Other data show, that under AI, there is only a suppression of
      estradiol of about 40-50% with an increase of testosterone of about 50%. Among men on AIs, it
      is possible that the hypothalamic-pituitary feedback loop results in an increase substrate
      for aromatisation, and thus prevents complete estrogen suppression.

      However, an optimal suppression (80%) of the peripheral estradiol level would be a necessary
      condition for a therapeutic benefit of AI in men with breast cancer.

      By adding a gonadotropin-releasing hormone analogue, the negative feedback loop would be
      interrupted and complete estrogen suppression may be achieved.

      In conclusion, there is a great lack on information for the treatment of male patients with
      breast cancer.

      Prospective multi-centre, randomised trials in men with breast cancer are necessary in order
      to prove the effect of tamoxifen + GnRH analogue versus none and versus AI + GnRH analogue as
      adjuvant or neoadjuvant endocrine treatment.
    

Intervention name(s): Tamoxifen; Tamoxifen and GnRH analogue; Exemestane and GnRH analogue
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 25 mg daily.; 25 mg Tamoxifen daily and GnRH analogue:
Goserelin (10.8 mg s.c. after randomisation and after three months) or
Leuprorelin (11.25 mg s.c. after randomisation and after three months).; 25 mg Exemestane daily and GnRH analogue:
Goserelin (10.8 mg s.c. after randomisation and after three months) or
Leuprorelin (11.25 mg s.c. after randomisation and after three months).
Other intervention name(s): TRENATONE, ZOLADEX; AROMASIN, TRENATONE, ZOLADEX.
Intervention MeSH terms: Tamoxifen; Goserelin; Exemestane; Prolactin Release-Inhibiting Factors
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Male breast cancer; neoadjuvant, adjuvant or metastatic situation; anti-hormonal therapy