Mifepristone for Breast Cancer Patients With Higher Levels of Progesterone Receptor Isoform A Than Isoform B.
Status:
Completed
Trial end date:
2019-10-31
Target enrollment:
Participant gender:
Summary
- Seventy per cent of breast cancers express estrogen (ER) and progesterone receptors (PR)
and respond to endocrine treatment.
- Actual therapy targets ER.
- There is enough evidence that progestins participate regulating breast cancer growth.
- Antiprogestins block cell proliferation and increase apoptosis in breast cancer models
which express high levels of PRA.
- Antiprogestins have been used to treat breast cancer patients that failed to other
treatments; benefits were seen in selected patients.
- Mifepristone (MFP) is currently used for medical abortion and for the treatment of
Cushing disease.
- MFP might exert agonistic effects when PRB isoform is activated by cAMP. This makes
mandatory the evaluation of the PR isoform ratio in breast cancer patients in which MFP
is a therapeutic possibility.
Main Goal To evaluate if therapeutic doses of MFP exert beneficial effects on breast cancers
expressing levels of PRA higher than those of PRB, evaluated as an inhibition in
proliferation markers and/or an increase in apoptotic markers.
- Eligibility
- Postmenopausal women (one year after menses stop).
- Women with tumors showing ratios of PRA/PRB higher than 1.5 and PR higher than 50%.
- Women without previous treatment.
- All clinical stages with tumors larger than 1.5 cm.
- Patients without autoimmune diseases and/or asthma.
- Study design
- Open Interventional.
- Twenty women will take MFP (200 mg) p.o. once /day during 14 days. As for
preliminary studies, to reach this number the investigators will have to evaluate
80-100 patients.
- Surgery is performed 14 days after treatment initiation, 24 hs after last dose.
- PR isoform ratio will be evaluated by western blots (WB) in one core biopsy.
Additional cores will be used for diagnosis, immunohistochemistry (IHC) of PR,
Ki-67 and other markers.
- At surgery samples will be frozen for molecular studies and fixed and processed for
pathological evaluation.
- Wilcoxon signed rank test will be used to evaluate differences in biomarker
expression between core biopsy and surgical samples of each patient.
- Blood will be collected before treatment initiation and prior to final surgery.
- Mammographic and echographic studies will be carried out before and after
treatment.
Phase:
N/A
Details
Lead Sponsor:
Hospital Provincial Magdalena V. de Martínez
Collaborators:
Agencia Nacional de Promoción de Ciencia y Tecnología, MINCYT Instituto de Biología y Medicina Experimental (IBYME-CONICET) National Agency for Scientific and Technological Promotion, Argentina