A drug used for emergency contraception and to treat fibroids may reduce biological signs linked to aggressive breast cancers in premenopausal women, a new study reports. Researchers found that ulipristal acetate — commonly called the “morning‑after pill” — lowered the activity of breast cells thought to give rise to hard‑to‑treat tumors and changed breast tissue structure and stiffness.
Study design
The Breast Cancer–Anti‑Progestin Prevention Study 1 (BC‑APPS1) was conducted at a single center in Manchester, U.K., to test whether blocking progesterone could reduce markers of breast cancer risk. Participants were 25–45 years old, still menstruating, and had a moderately to highly increased lifetime breast cancer risk (about 1 in 4 on average) because of family history. Of 32 enrolled between 2016 and 2019, 26 began treatment and 24 completed the study.
Each participant took 5 mg of ulipristal acetate daily for 12 weeks, starting on the first day of their period. Small needle biopsies of breast tissue were taken before treatment and after the 12‑week course (from opposite breasts), with the first biopsy timed to the phase of the cycle when progesterone is normally highest. Researchers analyzed cell counts and proliferation, gene and protein changes—especially in the extracellular matrix—and collagen arrangement and tissue stiffness. MRI and mammogram data were also reviewed for changes in breast density.
Key findings
– Cell proliferation dropped substantially: average proliferating cells fell from 8.2% before treatment to 2.9% after.
– Luminal progenitor cells, implicated as a likely origin of triple‑negative and other aggressive cancers, declined from 43% to 30% of breast cells. Other cell types were largely unchanged.
– Functional assays showed fewer mixed colonies (from 70% to 55%) and about a 50% reduction in mammosphere formation, indicating lower progenitor activity.
– Gene and protein analyses indicated altered behavior of hormone‑sensing cells and reduced production of key collagen proteins, notably collagen VI, which affects tissue architecture.
– There were fewer collagen‑related signals to stromal cells (for example reductions in signaling molecules such as WNT5A), and fibroblasts made less collagen in turn. Physically, collagen fibers were less aligned and tissue stiffness decreased.
– The greatest reductions in high‑risk progenitor cell activity were seen in women who began the study with denser breasts.
– Lab experiments supported a model in which tissue stiffness amplifies progesterone’s effects on progenitor cells; both ulipristal acetate and another anti‑progesterone drug interrupted the cycle linking stiffness, progesterone signaling, and progenitor growth.
– No serious side effects were reported in this small trial.
Implications and expert commentary
The authors suggest these changes could represent a novel preventive approach for younger, premenopausal women at elevated risk. However, clinicians not involved in the study emphasized that more data are needed before adopting ulipristal acetate for prevention.
Sagun Shrestha, MD, Chief of Medical Oncology at City of Hope Cancer Center in Phoenix, noted the continued importance of regular exams and recommended mammography and prompt evaluation of any abnormalities. She also advised minimizing hormone replacement therapy when possible.
Metin Çakmakçi, a breast surgical oncologist in Istanbul, highlighted other established risk‑reduction strategies: breastfeeding can modestly lower risk for women who have children; certain preventive medications (tamoxifen for premenopausal women, raloxifene and aromatase inhibitors for postmenopausal women) can reduce risk but have side effects that require specialist discussion; and very high‑risk individuals (for example BRCA1/2 mutation carriers) may consider prophylactic surgeries such as mastectomy or oophorectomy, which can produce substantial risk reduction.
Limitations and next steps
This was a small, single‑center trial with short follow‑up and biological end points rather than direct evidence of fewer cancers. The authors and outside experts say larger, longer studies are needed to confirm whether ulipristal acetate can safely and effectively reduce actual breast cancer incidence and to define which individuals would benefit most. In the meantime, tailored screening and discussion of existing prevention options remain the standard approach for people at elevated risk.
