Metastasis to bone is a frequent problem of advanced
breast cancer. Particularly breast
cancers, which do not express
estrogen and
progesterone receptors and which have no overexpression/amplification of the HER2-neu gene, so called
triple-negative breast cancers, are considered as very aggressive and possess a bad prognosis. About 60% of all human breast
cancers and about 74% of
triple-negative breast cancers express receptors for
gonadotropin-releasing hormone (
GnRH), which might be used as a therapeutic target. Recently, we could show that bone-directed invasion of human
breast cancer cells in vitro is time- and dose-dependently reduced by
GnRH analogs. In the present study, we have analyzed whether
GnRH analogs are able to reduce
metastases of
triple-negative breast cancers in vivo. In addition, we have evaluated the effects of
GnRH analogs on
tumor growth. To quantify formation of
metastasis by triple-negative MDA-MB-435 and MDA-MB-231 human breast
cancers, we used a real-time PCR method based on detection of human-specific alu sequences measuring accurately the amount of human
tumor DNA in athymic mouse organs. To analyze
tumor growth, the volumes of
breast cancer xenotransplants into nude mice were measured. We could demonstrate that
GnRH analogs significantly reduced
metastasis formation by
triple-negative breast cancer in vivo. In addition, we could show that
GnRH analogs significantly inhibited the growth of
breast cancer into nude mice. Side effects were not detectable. In conclusion,
GnRH analogs seem to be suitable drugs for an efficacious
therapy for triple-negative,
GnRH receptor-positive human breast
cancers to prevent
metastasis formation.