A small clinical study found that the drug ulipristal acetate — widely known as a morning‑after pill and also used to treat fibroids — reduced several biological signs associated with higher risk of aggressive breast cancers in premenopausal women.
Study design
The trial, called the Breast Cancer–Anti‑Progestin Prevention Study 1 (BC‑APPS1), was run at a single center in Manchester, U.K., to test whether blocking progesterone could alter tissue markers linked to breast cancer risk. Women aged 25–45 who were still menstruating and had a moderately to highly increased lifetime breast cancer risk (about 1 in 4 on average due to family history) were eligible. Of 32 enrolled between 2016 and 2019, 26 began treatment and 24 completed it.
Participants took 5 mg of ulipristal acetate daily for 12 weeks, beginning on the first day of their menstrual cycle. Needle biopsies of breast tissue were obtained before treatment and after 12 weeks (samples taken from opposite breasts), with the baseline biopsy timed to the luteal phase when progesterone is typically highest. Investigators measured cell counts and proliferation, cell populations (including progenitor cells), gene and protein expression—focusing on extracellular matrix components—collagen organization and tissue stiffness. MRI and mammogram images were also reviewed for density changes.
Key findings
– Proliferation fell markedly: the average percentage of proliferating breast cells dropped from 8.2% at baseline to 2.9% after treatment.
– The proportion of luminal progenitor cells, a population implicated as a likely source of triple‑negative and other aggressive cancers, decreased from 43% to 30% of breast cells; other major cell populations were largely unchanged.
– Functional assays showed reduced progenitor activity: mixed colony formation declined (about 70% to 55%) and mammosphere formation fell by roughly half.
– Molecular analyses revealed altered behavior of hormone‑sensing cells and lower production of key collagen proteins, especially collagen VI, which influences tissue architecture.
– Signaling from epithelial cells to stromal fibroblasts (for example changes in WNT5A and related signals) was reduced, and fibroblasts produced less collagen. Collagen fibers became less aligned and measured tissue stiffness decreased.
– The largest decreases in high‑risk progenitor activity occurred in women who started with denser breasts.
– Laboratory experiments supported a model in which tissue stiffness amplifies progesterone’s stimulation of progenitor cells; both ulipristal acetate and a different anti‑progesterone agent interrupted the feedback loop linking stiffness, progesterone signaling and progenitor growth.
– No serious adverse events were reported in this small trial.
Implications and expert perspectives
The investigators propose that anti‑progesterone treatment could offer a novel prevention strategy for younger, premenopausal women at elevated risk, by reducing progenitor cell activity and remodeling the tissue environment that supports aggressive tumor development. Outside clinicians stressed that these biological changes do not yet prove fewer cancers will occur, and that larger, longer trials are required before using ulipristal acetate for prevention.
Sagun Shrestha, MD, emphasized continuing routine screening — regular exams and mammography — and prompt evaluation of any breast changes, along with caution about hormone replacement therapy when possible. Metin Çakmakçi noted established prevention options: breastfeeding (which modestly lowers risk for those who have children), preventive medications such as tamoxifen (for premenopausal women) and raloxifene or aromatase inhibitors (for postmenopausal women) — all of which have benefits and side effects that require specialist discussion — and, for very high‑risk individuals (for example BRCA1/2 carriers), surgical options like prophylactic mastectomy or oophorectomy.
Limitations and next steps
BC‑APPS1 was small, single‑center, short in duration, and used biological markers rather than cancer incidence as the endpoint. The authors and independent experts agree that larger, multi‑center, longer trials are needed to determine whether ulipristal acetate can safely and effectively reduce actual breast cancer rates and to identify who might benefit most. Until then, personalized screening and counseling about established prevention strategies remain the standard for people at increased risk.
