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: 0
• Participant gender: Female

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
• Accepts Healthy Volunteers?: No

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
• Treatments: Mifepristone; Progesterone

Criteria

Inclusion Criteria:

• Inclusion criteria

1. Postmenopausal women (one year after menses stop)

2. Confirmed diagnosis of breast cancer

3. Tumors with higher expression PR > 50 % measured by IHC and PRA/RPB ratio equal or higher than 1.5 measured by WB

4. All clinical stages with tumor size greater than 1.5 cm to allow obtaining material from biopsy cores

5. OMS condition: 1 Adequate function of organs and systems

Hematopoietic parameters:

• Hemoglobin: 10 gr/mL

• Neutrophil counting: 1.500/mm3

• CD4 counting: 400/mm3

• Platelets counting: 100.000/mm3 Liver parameters

• Total albumin: 1.5 fold normal limit

• AST/ALT: 1.5 fold normal limit Renal

• Creatinine: 1.5 fold normal limit 6. Absence of other controlled disease 7. Patients willing to sign consent

Exclusion Criteria:

• Exclusion criteria

1. Patients with no recommended surgery

2. Patients which have received any other treatment for this cancer

3. Patients expressing ER but expressing PRA/PRB levels lower than 1.5

4. Hepatitis infection (HBV o HCV)

5. HIV infection.

6. Cognitive alterations which limit the understanding of the protocol or compliance to the protocol

7. Prolonged QT/QTc basal interval