Breast cancer screening – Steroid membrane bound receptors may predict the risk for certain types of cancer

Based on our first publications on experiments which have shown that certain progestogens can increase the estrogen-induced proliferation in the presence of special „Membrane-bound progesterone receptors“, an EDITORIAL in the journal „Menopause“ (Journal of the North American Menopause Society) suggested, that those receptors might explain the result of the WHI study, i.e. the increased breast cancer risk during treatment with estrogens combined with MPA (F.Stanczyk, Menopause 2011,18:833-834). Our further experiments showed no increase of proliferation using natural progesterone (X.Ruan, Congress of the German Society of Senology 2011;8:47, scientific award: poster prize), in contrast to a variety of synthetic progestogens comparing head to head in the same experiments (X.Ruan, Climacteric 2012, 15:467-472) Those primary experiments (published up to 2013) we performed in vitro investigating breast cancer cells, transfected with progesterone-membrane-receptor-component-expression-plasmid, using different types of malignant breast cells.

We now for the first time got similar results also in animal models, and in addition we also investigated tissue of breast cancer patients comparing with their benign breast tissue. We find that cancer cells of patients often highly express „Membrane bound progesterone receptors“ in contrast to benign breast cells and stromal tissue of the same breast cancer patients. In addition we also were able to confirm that those membrane-bound receptors not only can mediate and strongly stimulate the proliferation by the use of certain synthetic progestogens but also of estrogens, dependent on dosage and duration of use. So another recent EDITORIAL discussing our experiments in the journal „Menopause“ suggested to rename those receptors as „Steroid-membrane-bound receptors“ expressing sexual steriod-family effects under certain cell conditions (Th.Price; Menopause 2013; 20:486-487). However, we found that the proliferation by estrogen-only therapy is relatively slow; even in the presence of those crucial receptors it needs at least 10-15 years to get clinical cancer. So protection mechanisms (like estrogen-induced apoptosis) can work and delete the malignant proliferating cells before they grow up to clinical cancer. Only women with lack of sufficient protective mechanisms would have an increased risk using estrogen-only therapy. This might explain the results of the WHI-estrogen-only arm where a decrease of breast cancer risk has been observed. In contrast with the addition of certain synthetic progestogens we find rapid proliferation which may lead to clinical cancer before protection mechanisms sufficiently can work. The importance of progestogen addition also can explain that we find stronger proliferation with continuous combined compared to sequential combined hormone therapy regimens. The neutral effect of progesterone and higher risk of continuous combined HRT also could be seen in the recent clinical studies. In conclusion we suggest, that the „Steroid-membrane bound receptors“ could predict certain types of breast cancer induced especially by certain synthetic progestogens. We just now are trying to establish an assay to assess the receptors or components also in the blood for breast cancer screening before starting HRT and thereafter want to compare the results in patients with and without those receptors in a clinical comparative prospective study.