Mifepristone Treatment for Breast Cancer Patients Expressing Levels of Progesterone Receptor Isoform A (PRA) Higher Than Those of Isoform B (PRB): Neoadjuvant Therapy.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Measurable decrease in tumor cell proliferation from baseline to time of surgery
研究概览
简要总结
- 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.
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Eligibility
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Postmenopausal women (one year after menses stop).
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Women with tumors showing ratios of PRA/PRB higher than 1.5 and PR higher than 50%.
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Women without previous treatment.
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All clinical stages with tumors larger than 1.5 cm.
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Patients without autoimmune diseases and/or asthma.
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Study design
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Open Interventional.
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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.
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Surgery is performed 14 days after treatment initiation, 24 hs after last dose.
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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.
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At surgery samples will be frozen for molecular studies and fixed and processed for pathological evaluation.
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Wilcoxon signed rank test will be used to evaluate differences in biomarker expression between core biopsy and surgical samples of each patient.
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Blood will be collected before treatment initiation and prior to final surgery.
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Mammographic and echographic studies will be carried out before and after treatment.
详细描述
Hypothesis
PR are involved in breast cancer growth. The antiprogestin mifepristone (MFP) exerts antitumor effects in mammary carcinomas with high expression of PRA. The investigators hypothesize that breast cancers with higher levels of PRA than PRB will benefit from an antiprogestin therapy.
Precis
The aim of the study is to select 20 breast cancer patients, with primary tumors expressing PR (50% or higher) and 1.5 fold PRA as compared with PRB, for a neoadjuvant treatment with mifepristone (MFP) during 14 days in between biopsy core and surgery. There are no studies at the present time selecting breast cancer patients according to the prevailing PR isoform expressed. This is extremely important since antiprogestins might have no effect or even stimulate those over-expressing PRB.
Background
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Inclusion criteria
- •Postmenopausal women (one year after menses stop)
- •Confirmed diagnosis of breast cancer
- •Tumors with higher expression PR > 50 % measured by IHC and PRA/RPB ratio equal or higher than 1.5 measured by WB
- •All clinical stages with tumor size greater than 1.5 cm to allow obtaining material from biopsy cores
- •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
- •Absence of other controlled disease
- •Patients willing to sign consent
排除标准
- •Exclusion criteria
- •Patients with no recommended surgery
- •Patients which have received any other treatment for this cancer
- •Patients expressing ER but expressing PRA/PRB levels lower than 1.5
- •Hepatitis infection (HBV o HCV)
- •HIV infection.
- •Cognitive alterations which limit the understanding of the protocol or compliance to the protocol
- •Prolonged QT/QTc basal interval
研究组 & 干预措施
Mifepristone
Tablets of Mifepristone 200 mg p.o. once a day during 14 days between biopsy and surgery after confirming inclusion criteria
干预措施: Mifepristone (Drug)
结局指标
主要结局
Measurable decrease in tumor cell proliferation from baseline to time of surgery
时间窗: Baseline to time of surgery (14 days of treatment between biopsy core and surgery)
Treatment efficacy will be assessed by comparing tissue samples from the baseline biopsy and tissue samples collected from the day of surgery, evaluating if there is a decrease in the proliferating index (Ki-67 expression by immunohistochemistry). Positive response: differences higher than 30%.
次要结局
- Measurable increases in apoptotic markers from baseline to time of surgery(Baseline to time of surgery (14 days of treatment between biopsy core and surgery))
- Measurable changes in signaling pathways downstream PR(Baseline to time of surgery (14 days of treatment between biopsy core and surgery))