A prospective, randomised, multi-centre phase II trial to evaluate oestradiol suppression in the case of (neo)adjuvant and palliative treatment with tamoxifen alone versus tamoxifen plus GnRH analogue versus aromatase inhibitor plus GnRH analogue for male breast cancer patients.
Breast cancer in men accounts for approximately 0.5-1% of all diagnosed cases. Around 400 to 450 new cases are diagnosed in Germany every year. Male breast cancer is often more advanced at the time of diagnosis than female breast cancer; around 40% of female cases are diagnosed at stages III or IV. This discrepancy is probably due to a lack of knowledge about the disease both on the part of patients, leading them to delay consulting a doctor, and on the part of physicians. This leads to delayed confirmation of diagnosis. In the majority of patients, ductal invasive (90%), hormone-receptor-positive (90%), HER2-negative (90%) breast cancer is diagnosed.
There is very little information available on the treatment of male breast cancer. Some data is based on retrospective case reports and retrospectively initiated trials with limited case numbers or inhomogeneous trial cohorts. Consequently, treatment standards are not derived from large, prospective, randomised trials and the optimal therapy for this patient group is unknown.
As a result, men with breast cancer are currently treated in accordance with the therapy guidelines developed for women. Tamoxifen 20 mg for a period of five years is the standard endocrine therapy. However, numerous cases of therapy discontinuation have been observed owing to the side-effect profile. It has also been established that in both men and women there is differing enzymatic activity in the metabolism of tamoxifen to the active metabolite endoxifen via the cytochrome P450 2D6. It is likely that some patients do not benefit from standard therapy with tamoxifen.
The use of aromatase inhibitors has further improved disease-free survival and overall survival in women with hormone-receptor-positive breast cancer compared with the use of tamoxifen alone. However, information about aromatase inhibitor treatment for breast cancer in men is limited to case reports. Data from trials conducted by other bodies show that the oestradiol level in men receiving aromatase inhibitors only falls by around 50 to 80% and that the testosterone level increases by around 50%. This may be due to the fact that in men the aromatase inhibitor affects the regulatory loop between the hypothalamus and the pituitary gland, leading to an increase in the substrates formed by aromatisation and thus preventing the oestrogen level from falling completely. However, the oestradiol level needs to be reduced by around 80% for a therapy effect to be assumed in this patient population. Additional administration of a GnRH analogue impedes the regulatory loop between the hypothalamus and the pituitary gland, thus entirely suppressing oestrogen production.
Overall there is a significant lack of reliable data and therapy guidelines for treating male breast cancer. Large-scale, prospective, randomised trials are therefore needed to close this gap and to examine the efficacy of anti-hormone therapy with tamoxifen alone or in combination with a GnRH analogue, or an aromatase inhibitor plus a GnRH analogue in men with hormone-sensitive breast cancer.
Status: Recruitment in progress
The first patient was recruited to the MALE trial on 22/10/2012 by the Marienhospital Witten (Coordinating Investigator: Dr. J. Hackmann / Trial Assistants: Ms. K. Fritz, Ms. J. Nölken).
Please note that the participating sites have already been selected for this trial. Even if your clinic / practice is not a MALE site, you are kindly requested to contact us should you wish your male breast cancer patients to be recruited to the trial.
The trial is being conducted at the following sites:
Please get in touch with us if you wish to receive the necessary contact details.
48 patients from around 35 sites are to be included in the trial. So far, 30 patients have been recruited (as at December 2015).
Please also recruit male breast cancer patients to the register trial being conducted by the University of Magdeburg. Simultaneous participation in both trials is possible!
Further information for participating sites can be found in the password-protected section of this website for internal use.
The following trial-related documents can be downloaded here.
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