Breast Cancer - Anti-Progestin Prevention Study 1 (BC-APPS1)

NHS Foundation Trust

Status and phase

Completed

Phase 2

Conditions

Breast Cancer

Treatments

Drug: ulipristal acetate

Study type

Interventional

Funder types

Other

Identifiers

NCT02408770

2016BS001 (Other Identifier)

UHSM0315

Details and patient eligibility

About

The primary objective of this study is to determine the effects of the antiprogestin ulipristal acetate (UA) on the epithelial and stromal compartments of the normal breast in women at increased risk of breast cancer (BC) and to relate these effects to quantitative changes on multiparametric magnetic resonance imaging (MRI). The goal is to define predictive imaging biomarkers for subsequent testing in randomised prevention trials of antiprogestins.

Full description

Breast cancer (BC) is the commonest cancer, affecting 1.4 million women per year of whom a third die from the disease. There is an urgent need for new approaches to BC prevention. Progesterone is a hormone that is produced naturally from a woman's ovaries during each menstrual cycle and is often used in hormone replacement therapy (HRT) after the menopause. When used in HRT progesterone increases the risk of BC and BC death. In experiments in mice and rats progesterone has been shown to increase the growth of the normal mammary gland (the rodent breast). When human breast tissue is grown in the laboratory it also grows in response to progesterone. In particular progesterone has been shown to increase the growth of particular cells called stem cells which survive for a long time in the breast. It is thought that the exposure of these stem cells to progesterone over many years is the reason that women whose periods start early and finish late or those who do not have a pregnancy to interrupt their menstrual cycles and those that take HRT all have an increased risk of BC.

In this project the investigators will use a drug that blocks the effects of progesterone called ulipristal acetate (UA, EsmyaTM) that is currently licenced in the treatment of fibroids of the uterus. When used to treat fibroids UA is very well tolerated with no increase in side effects compared to a placebo tablet. 30 women at increased risk of BC will be recruited and have magnetic resonance imaging (MRI) scan and mammogram followed by a biopsy of one breast. After 3 months of UA treatment the MRI will be repeated along with a biopsy from the other breast. The effects of UA on many different cell types in the biopsies, including the stem cells and also the tissues like collagen that support them will be examined in detail. The effects of UA treatment on gene and protein expression in the breast tissue will also be examined. The goal is to identify which women will be sensitive or resistant to UA as a BC prevention treatment. In addition changes in the MRI scans with UA treatment will be examined using several different analysis techniques to try and identify who will likely benefit from UA treatment in the future without the need for biopsies.

Enrollment

24 patients

Sex

Female

Ages

25 to 45 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Premenopausal females aged between 25 and 45 years
Regular menses
Known BRCA1 or BRCA2 mutation or moderate to high risk of developing BC defined as >17% lifetime risk from age 20 or >3% risk between 40-50 years
Ovulatory menstrual cycles
eGFR ≥ 40mls/min/1.73m2

Exclusion criteria

Personal history of breast, uterine, cervical or ovarian cancer
Breast feeding within the last 3 months
Pregnant or planning for pregnancy in the next 6 months.
Known hypersensitivity to radiological contrast media or to ulipristal acetate or its excipients
Current treatment with:

Anti-estrogens, GnRH analogues or hormonal contraceptives, corticosteroids or antiplatelet/anticoagulant therapy or moderate or potent inhibitors or inducers of CYP3A4

APTT and PT outside the normal institutional ranges. Hb <100g/l and platelet count <150x109/l. Serum creatinine, bilirubin, ALT, ALP or LDH >1,5xULN.
Contraindications to MRI
Prior breast enhancement/augmentation surgery
Genital bleeding of unknown aetiology