Clinical trial NCT01898312: BRCA1/2 and Effect of Mifepristone on the Breast
Official title: The Effect of a Progesterone Receptor Modulator on Breast Tissue in Women With BRCA-1 and -2 Mutations - a Placebo Controlled RCT.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Women With Mutations in the Breast Cancer Susceptibility Genes BRCA1,2
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
First posted: 2013-07-12
Enrollment: 45
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: epithelial cell proliferation in breast tissue
timeFrame: 3 months
Secondary outcomes:
measure: Vital signs and safety lab analysis
timeFrame: 3 months
measure: Side effects and Adverse Events
timeFrame: 3 months
measure: Endometrial effects
timeFrame: 3 months
measure: Ovarian effects
timeFrame: 3 months
measure: Breast symptom evaluation
timeFrame: 3months
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Department of Woman and Child Health Karolinska University Hospital
Study officials:
affiliation: Dept of Womens and Childrens Health Karolinska Institutet
name: Kristina Gemzell Danielsson, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Dept of Womens and Childrens Health, Karolinska Institutet
name: Angelique Flöter Rådestad, MD PhD
role: STUDY_CHAIR
References:
citation: Engman M, Skoog L, Soderqvist G, Gemzell-Danielsson K. The effect of mifepristone on breast cell proliferation in premenopausal women evaluated through fine needle aspiration cytology. Hum Reprod. 2008 Sep;23(9):2072-9. doi: 10.1093/humrep/den228. Epub 2008 Jun 24.
citation: Isern AE, Loman N, Malina J, Olsson H, Ringberg A. Histopathological findings and follow-up after prophylactic mastectomy and immediate breast reconstruction in 100 women from families with hereditary breast cancer. Eur J Surg Oncol. 2008 Oct;34(10):1148-54. doi: 10.1016/j.ejso.2008.03.002. Epub 2008 Apr 23.
citation: Kauff ND, Brogi E, Scheuer L, Pathak DR, Borgen PI, Hudis CA, Offit K, Robson ME. Epithelial lesions in prophylactic mastectomy specimens from women with BRCA mutations. Cancer. 2003 Apr 1;97(7):1601-8. doi: 10.1002/cncr.11225.
citation: Poole AJ, Li Y, Kim Y, Lin SC, Lee WH, Lee EY. Prevention of Brca1-mediated mammary tumorigenesis in mice by a progesterone antagonist. Science. 2006 Dec 1;314(5804):1467-70. doi: 10.1126/science.1130471.
citation: Bartlett TE, Evans I, Jones A, Barrett JE, Haran S, Reisel D, Papaikonomou K, Jones L, Herzog C, Pashayan N, Simoes BM, Clarke RB, Evans DG, Ghezelayagh TS, Ponandai-Srinivasan S, Boggavarapu NR, Lalitkumar PG, Howell SJ, Risques RA, Radestad AF, Dubeau L, Gemzell-Danielsson K, Widschwendter M. Antiprogestins reduce epigenetic field cancerization in breast tissue of young healthy women. Genome Med. 2022 Jun 15;14(1):64. doi: 10.1186/s13073-022-01063-5.