Mifepristone treatment for breast cancer patients expressing levels of progesterone receptor isoform A (PRA) higher than those of isoform B (PRB)

HUGO GASS; VICTORIA FABRIS; SILVIA LOVISI; ALFREDO MOLINOLO; CARLA VENTURA; CAROLINE LAMB; JAVIER BURRUCHAGA; ALEJANDRA CASTETS; INES CAILLET BOIS; ANDRES ELIA; PAULA MARTINEZ VAZQUEZ; MARCOS DANIEL LIGUORI; CLAUDIA LANARI; VIRGINIA NOVARO; GABRIELA ACOSTA HAAB; GUSTAVO SAN MARTIN; PEDRO GONZALEZ; PAOLA ROJAS

Chicago

Congreso; ASCO Annual Meeting; 2017

ASCO

Background: Seventy percent of breast cancers express estrogen (ER) and progesterone receptors (PR) and respond to antiestrogen therapies. Emerging evidence from experimental studies and human epidemiology, points to a relevant role for progestins in breast carcinogenesis and cancer growth. Others and we have proposed that there is a role for antiprogestins in the therapeutic armamentarium, but the challenge remains to identify which patients would benefit from targeting the PR in addition to ER. Preclinical data indicates that antiprogestins block cell proliferation and increase apoptosis only in ER+ breast cancers expressing levels of PRA higher than those of PRB. The aim of this study is to evaluate the therapeutic effects of Mifepristone (MFP), an antiprogestin currently used for the treatment of Cushing´s disease and for medical abortion, on breast cancer patients selected by their PRA/PRB isoform ratio, for 14 days in between core biopsy and surgery (MIPRA trial: NCT02651844). Methods: This is an open label, interventional with single group assignment study. We perform core biopsies on menopausal patients with clinically palpable breast cancers larger than 1.5 cm to confirm diagnosis. We will assess the PRA/PRB ratio by western blotting in frozen samples and total PR in formalin-fixed samples by immunohistochemistry (IHC). Twenty eligible PR+ patients (PR > 50 %) with PRA/PRB ≥1.5 who have signed consent forms, and meet the inclusion criteria will be recruited. Patients will be treated for 14 days with MFP p.o 200 mg. Surgery will be performed on day 15. Samples will be frozen for molecular studies or fixed for IHC. The primary outcome is the evaluation of Ki-67 staining pre- and post treatment. Secondary outcomes include comparatively expression of proliferation/apoptosis/PR signaling markers in core and surgical biopsy samples. Other pre-specified outcomes include molecular profiling, study of liquid biopsies, mammography, and ultrasound studies. Wilcoxon signed rank test will be used to evaluate differences in biomarker expression between core biopsy and surgical samples of each patient.