Hormone therapy may increase the risk of
breast cancer. Thus, especially the addition of
synthetic progestins may play a decisive role according to the results of clinical studies. Overexpression of a special receptor, i.e. the
progesterone receptor membrane component-1 (PGRMC1), may offer a potential new pathway to explain the observed increase in
breast cancer risk in the combined arm of the Women's Health Initiative. PGRMC1 is expressed in
breast cancer tissue and may be important in
tumorigenesis. The expression of PGRMC1 in
breast cancer tissue is significantly different from that in normal mammary glands. Certain
synthetic progestins can increase the proliferation of PGRMC1-overexpressing
breast cancer cells and may thus be involved in
tumorigenesis, while
progesterone and certain
synthetic progestins such as
nomegestrol or
chlormadinone acetate react neutrally. Our investigations point towards an important role of
estrogen receptor-α in the signaling cascade, resulting in the proliferative effect induced by
progestins. Thus, activation of PGRMC1 may explain the increased
breast cancer risk observed during treatment with certain
progestins. Very recently, PGRMC1 was investigated in serum samples of
lung cancer patients and matched healthy patients; significantly higher concentrations were shown in the
cancer patients. Therefore, PGRMC1 might be a predictor for other
cancers as well but, according to clinical trials, its importance for a possible screening tool, particularly for
breast cancer risk during
hormone therapy, seems of interest.