Ulipristal acetate does not impact human normal breast tissue.

Area of Science:

• Endocrinology
• Gynecology
• Oncology

Background:

• Antiprogestins, like ulipristal acetate (UPA), are increasingly relevant for gynecological treatments.
• UPA's potential long-term use in contraception and uterine fibroid treatment necessitates understanding its effects on breast tissue.
• Hormonal dysfunction is linked to breast pathologies, highlighting the need to assess chronic UPA therapy's secondary consequences.

Purpose of the Study:

• To investigate the actions of ulipristal acetate (UPA) mediated by progesterone receptor (PR) and glucocorticoid receptor (GR).
• To determine UPA's effects on both normal and transformed breast cells.

Main Methods:

• Assessed effects of UPA, progesterone (P), and dexamethasone (DEX) on PR and GR responsive genes.
• Evaluated proliferation and apoptosis in normal human breast epithelial (HBE) cells and breast cancer cell lines.
• Utilized xenografted human normal breast tissue in athymic mice, treated with estradiol (E2), E2 + P, or E2 + P + UPA.

Main Results:

• UPA demonstrated anti-progestational and anti-glucocorticoid activity in both normal and cancer breast cells, more significantly in cancer cells.
• UPA inhibited normal HBE cell proliferation but promoted breast cancer cell line growth when combined with P or DEX.
• No impact on the mitotic index was observed in xenografted human breast tissue under conditions mimicking normal hormonal exposure.

Conclusions:

• Experimental models suggest UPA treatment may not be detrimental to normal breast tissue for short-term (28-day) continuous administration.
• Further clinical trials are necessary to validate these findings in women undergoing UPA therapy.