BRCA1/2 and Effect of Mifepristone on the Breast

Karolinska Institute

Status and phase: Completed; Phase 2

Conditions: Women With Mutations in the Breast Cancer Susceptibility Genes BRCA1,2

Treatments: Drug: Mifepristone

Study type: Interventional

Funder types: Other

Identifiers

NCT01898312

2012-003703-35

Details and patient eligibility

About

Ovarian steroids, as well as their synthetic counterparts gestagens and estrogens have a role in breast cell proliferation and the development of breast cancer. Here, the effect of a progesterone receptor modulator, mifepristone, on cell proliferation in human breast tissue in vivo will be studied in women with BRCA-1 or -2 mutations. Our preliminary results implicate a possible protective effect of mifepristone in breast epithelium. The ability of mifepristone to block breast epithelial cell proliferation may prevent tumorigenesis and may also prove beneficial when used for contraceptive purposes and on other indications. The proposed project concerns a Randomized Controlled Trial on mifepristone versus placebo treatment of women with BRCA-1or -2 mutations with a high risk/incidence of breast cancer and ovarian cancer.

Full description

Objectives • Research objective To study the safety and effect of treatment with mifepristone, a progesterone receptor modulator, on epithelial cell proliferation in human breast tissue in women with BRCA-1 or -2 mutations prior to protective mastectomy.

Project description

• Hypothesis/ Theory Mifepristone treatment exerts an antiproliferative, protective effect on breast tissue in women with BRCA-1 or -2 mutations

Study Design Randomized, double blind, placebo controlled trial. Women will be recruited among patients with BRCA-1 or -2 mutations scheduled for prophylactic mastectomy. Included women will be randomized to a 3-month treatment with mifepristone, 50 mg (Mifegyne, Exelgyn, Paris, France) or placebo taken orally every second day. Breast biopsies will be obtained in the luteal phase prior to start of treatment and again during surgery.

Enrollment: 45 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria:

• Pre-menopausal women, >/= 18 years of age
• with good general health and
• regular menstrual cycles (25-35 days) who are willing and
• able to participate after giving informed consent.
• women having BRCA1/2 mutation and have decided to undergo risk reducing mastectomy

Exclusion criteria includes:

• Any hormonal treatment used within 2 months prior to study start and
• Any contraindication to mifepristone

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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45 participants in 2 patient groups, including a placebo group

Mifepristone

Experimental group

Description:

treatment with oral mifepristone 50 mg every second day for 12 weeks in 30 women with BRCA 1 or 2 mutation

Treatment:

Drug: Mifepristone

TrioBe

Placebo Comparator group

Description:

treatment with a quarter of a tablet of TrioBe every second day for 12 weeks

Treatment:

Drug: Mifepristone