RANKL Inhibition and Mammographic Breast Density (TRIDENT)

  • End date
    Aug 31, 2026
  • participants needed
  • sponsor
    Washington University School of Medicine
Updated on 23 April 2022


Data supporting a role for RANKL signaling in mammographic density and breast cancer development has begun to emerge, but clinical trial data providing definitive evidence that would allow the adoption of RANKL inhibition in primary breast cancer prevention are not yet available. The hypothesis is that RANKL inhibition with denosumab will decrease mammographic density in high-risk premenopausal women with dense breasts. To address this, the investigators have developed this clinical trial to quantify the impact of RANKL inhibition on mammographic density in high-risk premenopausal women with dense breasts and to determine the effect of RANKL inhibition on markers of proliferation and biomarkers of breast cancer risk. Successful demonstration that RANKL inhibition reduces mammographic density could open up additional approaches to primary breast cancer prevention in high-risk premenopausal women, who do not have dominant genetic predisposition.

Condition Dense Breasts
Treatment Placebo, Blood draw, Vitamin D3, Denosumab, calcium, core needle biopsy
Clinical Study IdentifierNCT04067726
SponsorWashington University School of Medicine
Last Modified on23 April 2022


Yes No Not Sure

Inclusion Criteria

Premenopausal (when menopausal status is uncertain, the investigators will measure follicle-stimulating hormone and estradiol to ascertain that a partcipant is premenopausal)
At least 40 years of age
Dense breasts on routine mammogram (BI-RADS Category C and D, i.e. volumetric percent density ≥ 7.5% on Volpara)
Able to understand and willing to sign an IRB-approved written informed consent document

Exclusion Criteria

Pregnant, lactating, or planning to get pregnant while the trial is ongoing
History of ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS), invasive breast cancer, or other cancer (except non-melanoma skin cancer)
Known BRCA mutation(s)
Current use of tamoxifen, aromatase inhibitors, or bisphosphonates, or RANKL inhibitors
Concurrent participation in another cancer chemoprevention trial (unless no longer receiving the intervention)
Recent history of invasive dental procedure (e.g. tooth extraction, dental implant, oral surgery)
Unhealed and/or planned dental/oral surgery
History of osteonecrosis/osteomyelitis of the jaw
History of osteoporosis or severe osteopenia
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact



Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider


Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 



Reply by • Private

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note