Clinical importance of PGRMC1 in hormone responsive breast cancer

Background: For the development of PGRMC1, a multifunctional receptor belonging to membrane-associated progesterone receptor proteins (MAPR) family, as possible predictive marker for increased hormone-dependent breast cancer risk, a systematic research program has been performed, starting with different breast cancer (BC) cells, continued with animal studies and finally clinical studies with BC-patients. Summary: In-vitro studies showed dose- and time-dependent BC-cell proliferations with all available synthetic progestogens (not with progesterone), but mostly significant only in presence of PGRMC1. Different animal(xenograft) studies confirmed, that synthetic progestogens but not progesterone and dydrogesterone increased the estradiol-induced tumor-proliferation, although with dydrogesterone a small time-dependent increase could be seen. Clinical studies with hormone replacement therapy (HRT) to confirm these results are still running. In patients with BC expression of PGRMC1 in BC-tissue was correlated to tumor-characteristics like diameter, grade and metastatic status. BC-patients with PGRMC1 in the tumors had poorer disease-free and overall survival. After developing of an assay, blood-levels could be correlated to the expression in BC-tissue showing PGRMC1 superior to tumor markers such as CEA, CA125, CA153 and TPS. Key messages:This review is summarizing two different functions of PGRMC1: 1) to predict the prognosis of BC-patients, already well demonstrated in BC-patients and 2) being a possible predictive marker for BC risk during HRT as suggested from in-vitro and animal research.

Automated summary

This study systematically investigates the role of PGRMC1 in breast cancer. In vitro and animal experiments demonstrate that PGRMC1 plays a critical role in synthetic progestogen-induced breast cancer proliferation. Clinical studies show that the expression of PGRMC1 in breast cancer tissue is associated with tumor characteristics and patient survival. Therefore, PGRMC1 may serve as a predictive marker for the prognosis of breast cancer patients and the risk of breast cancer during hormone replacement therapy.