This phase II trial tests whether taking ulipristal acetate prior to a mammogram decreases breast density for people with a history of extremely dense breast tissue. One limitation to breast cancer screening with mammography is dense breast tissue, which decreases the sensitivity of screening as breast density masks cancer and precancerous lesions. Ulipristal acetate lowers the amount of progesterone made by the body which may temporarily decrease the density of the breast tissue, allowing for a more accurate mammogram for people with extremely dense breast tissue.

PRIMARY OBJECTIVE:

I. To evaluate change in percent dense area from antecedent to study screening mammograms.

SECONDARY OBJECTIVES:

I. To assess for menstrual cycle phase following this regimen of ulipristal acetate (UPA).

II. To assess adherence, tolerability and acceptability of the short course of UPA prior to a mammogram.

EXPLORATORY OBJECTIVES:

I. To determine the presence of radiographic changes in clinical breast density on screening mammograms following a course of UPA.

II. To characterize a change in background parenchymal enhancement (BPE) on breast magnetic resonance (MR).

III. To describe the effect of the intervention on routine clinical care. IV. To determine the longitudinal effect of the intervention on primary objective (clinical breast density score).

OUTLINE:

Patients receive ulipristal acetate orally (PO) every 5 days for 4 doses in the absence of unacceptable toxicity (study days 1, 5, 10 and 15). Patients then undergo a mammogram on study day 20. Patients also undergo base magnetic resonance imaging (MRI) and blood sampling which will be repeated on study day 20.

After completion of study intervention, patients are followed up at 1-7 days and may be followed up to 24 months for results of subsequent screening mammograms.

Inclusion Criteria:

• Participant or legally authorized representative (LAR) must provide written informed consent before any study-specific procedures or interventions are performed
• Ages 18-50 years. The maximum age cut off is due to the intervention only applying to premenopausal physiology only
• Assigned female at birth with at least one ovary in situ. Members of all races and ethnic groups will be included
• Presenting for a screening mammogram
• Has an antecedent mammogram within 24 months with a Breast Imaging Reporting and Data System (BI-RADS) breast composition score of Category D (extremely dense) for which images are available for analysis
• Report no history of breast cancer or symptoms concerning for breast cancer such as a self-palpated mass
• Reasonably assumed to be premenopausal by history of regular menses. For individuals who do not menstruate (due to hysterectomy or endometrial ablation), premenopausal status will be determined clinically by the absence of symptoms of menopause including weekly hot flashes which is consistent with clinical care

Exclusion Criteria:

• Having a mammogram as part of a diagnostic process
• Current breast implants in one or both breasts
• Pregnant, less than 1 year postpartum or breastfeeding within last 6 months at the time of their antecedent mammogram or their current mammogram. This exclusion is due to known changes in mammograms during pregnancy and postpartum that would preclude comparative analyses
• Using hormonal medications including estrogens or progestins
• History of allergy to UPA
• A history of liver disease (including but not limited to viral or autoimmune hepatitis, non-alcoholic fatty liver disease, hemochromatosis or Wilson's disease), alcoholism or a history of liver function tests such as aspartate aminotransferase (AST)/alanine aminotransferase (ALT) greater than 3 x the upper limit of normal without known etiology
• Attempting pregnancy during the study duration or a positive urine pregnancy for people at risk of pregnancy who cannot be reasonably assumed not to be pregnant at the beginning of the intervention
• Use of CYP3A4 inducer or inhibitors which may alter plasma concentrations of study drug (See Appendix A for list of common drugs/herbs). Regarding recent use of CYP3A4 inducers or inhibitors, a washout period will be deemed sufficient if at least 14 days or 5 half lives of the drug have elapsed prior to initiation of the study drug, whichever is longer. Participants will be advised to abstain from CYP3A4 inducers or inhibitors during the study and will only be ineligible if unable to