Women With Mutations in the Breast Cancer Susceptibility Genes BRCA1,2 Clinical Trial
Official title:
The Effect of a Progesterone Receptor Modulator on Breast Tissue in Women With BRCA-1 and -2 Mutations - a Placebo Controlled RCT.
| Verified date | January 2022 |
| Source | Karolinska Institutet |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 45 |
| Est. completion date | January 2022 |
| Est. primary completion date | December 31, 2021 |
| Accepts healthy volunteers | No |
| Gender | Female |
| Age group | 18 Years and older |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| Sweden | Department of Woman and Child Health Karolinska University Hospital | Stockholm |
| Lead Sponsor | Collaborator |
|---|---|
| Karolinska Institutet |
Sweden,
Engman M, Skoog L, Söderqvist 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. — View 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. — View 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. — View 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. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | epithelial cell proliferation in breast tissue | Changes from baseline after 12 weeks of mifepristone treatment in epithelial cell proliferation by measuring expression of genes specifically in the pathways involving apoptotic and cell proliferation by microarray study, including PTEN, Bcl-2 and Ki-67 along with steroid receptors. | 3 months | |
| Secondary | Vital signs and safety lab analysis | Safety data includes vital signs, general- and gynecological-, incl breast - examinations, safety lab (hematology (blood status+CRP), kidney function (Na, K, krea) liver function (ASAT, ALAT, ALP, GT, bilirubin) , thyroid function (TSH,T3,T4), hormonal values FSH ,LH , PRL, SHBG, testosterone, E2 (sensitive) progesterone, urine dipstick and pregnancy test (prior to start). Endometrial histology will be investigated in biopsies obtained at baseline and at surgery. Women with BRCA-1/-2 mutations are followed according to the existing clinical routine with regard to ovarian cancer screening. | 3 months | |
| Secondary | Side effects and Adverse Events | Side effects of mifepristone are mild and the only significant side effect reported in previous clinical trials with the same regimen has been mild flushes. All side effects and SAE/AE as well as any concomitant medication will be recoded by the participating patients in a dairy. | 3 months | |
| Secondary | Endometrial effects | Bleeding patterns and endometrial morphologywill be studied. Endometrial histology and progesterone receptor modulator associated changes will be investigated in biopsies obtained at baseline and at surgery. Bleeding pattern will be registered during the study period by the participating women. | 3 months | |
| Secondary | Ovarian effects | Women with BRCA-1/-2 mutations are followed according to the existing clinical routine with regard to ovarian cancer screening. | 3 months | |
| Secondary | Breast symptom evaluation | Breast symptom evaluation will be registered at baseline and during the study by a breast symptom score. | 3months |