Mammographic DensityKEEPS MDBHASNCT02524561
KEEPS Mammographic Density And Breast Health Ancillary Study
A study testing CEE pill, Estradiol patch and Active Progesterone in people with Mammographic Density and Abnormal Mammogram, run by Brigham and Women's Hospital at 1 site in United States.
Trial summary
Combined estrogen and progestin therapy has been shown to increase mammographic density and incidence of breast cancer in randomized trials. The investigators propose to examine the effects of now commonly used low-dose combined hormone therapy (HT) regimens on breast density, rates of abnormal mammogram, and… Read more about this study
- Who is it for?
- Ages 42 to 58 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Mammographic Density, Abnormal Mammogram
- What is being tested?
- CEE pill, Estradiol patch and Active Progesterone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 517 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2005to Dec 2013
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 42 to 58 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Women were 42-58 years of age, have had cessation of menses at or after age 40 and no menses for a minimum of 6 and a maximum of 36 months at screening.
- Subjects may or may not have had current vasomotor estrogen deficiency symptoms, had not taken estrogen- or progestogen-containing medication (oral contraceptive or hormone replacement) within 3 months of randomization, and had plasma FSH levels measured at ≥35 ng/ml and plasma E2 levels of <40 pg/ml.
Who cannot join
- Subjects were excluded for increased endometrial thickness on ultrasound >5 mm, unless endometrial biopsy was negative; for LDL ≥ 190 mg/dl or triglycerides ≥ 400 at screening, or use of lipid lowering drugs.
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospital
Boston, Massachusetts, 02115
About this study
Combined estrogen and progestin therapy has been shown to increase mammographic density and incidence of breast cancer in randomized trials. The investigators propose to examine the effects of now commonly used low-dose combined hormone therapy (HT) regimens on breast density, rates of abnormal mammogram, and circulating estrogens in the ongoing, already-funded Kronos Early Estrogen Prevention Study (KEEPS). KEEPS is a randomized clinical trial with a primary goal of examining the effects of low-dose transdermal versus oral estrogen combined with cyclic micronized progesterone on progression of subclinical atherosclerosis in recently menopausal women. Prior studies of low-dose HT have been of short duration and small size. By determining the effects of low-dose hormone therapy on the breast, the proposed ancillary study will add important information about the estimated balance of risks and benefits associated with low-dose HT and will help guide future research trials.
Read the detailed description
Despite data from clinical trials showing an increased risk of breast cancer and lack of overall benefit for primary prevention with hormone therapy (HT), there is still significant usage of HT by clinicians and women for treatment of moderate-to-severe systemic menopausal symptoms. Due to the possible increased risks with these preparations, current clinical recommendations advocate utilizing the lowest dose for the shortest possible duration, but average duration is often for 2-4 years. However, the effects of commonly used low-dose HT regimens on breast density and breast cancer risk are unknown. Recent data from intervention trials support the long standing hypothesis that hormonal effects on breast cancer risk are mediated through breast density. The Kronos Early Estrogen Prevention Study (KEEPS) is an ongoing, already- funded randomized clinical trial with a primary goal of examining the effects of 4 years of low- dose transdermal versus oral estrogen combined with cyclic micronized progesterone on progression of subclinical atherosclerosis in recently menopausal women. The proposed ancillary study will efficiently examine the effects of randomized low-dose HT on key breast cancer surrogate endpoints: mammographic density and rates of abnormal mammograms. In the parent KEEPS study, a total of 720 women were randomized to oral conjugated equine estrogens (0.45 mg/d), transdermal 17-beta estradiol (50 mcg/d), or placebo, with cyclic micronized progesterone (200 mg for 12 days) for active hormonal therapy groups. All participants were required to have mammography prior to study entry as well as yearly during follow-up; blood samples also were collected at these time points. Randomization was completed in 2008. In this ancillary study, we aimed to collect mammograms from eligible women consenting to be part of the ancillary study(n=517) from baseline, year 1 and year 3 will be obtained and processed centrally to calculate mammographic density. The investigators will determine if these two low-dose HT regimens are associated with change in mammographic density. The investigators will also examine if baseline mammographic density or circulating biomarkers including estradiol, estrone, and estrone sulfate, modify or mediate changes in breast density with HT. In addition, the effects of hormonal regimens on the rates of abnormal mammogram and biopsy will be determined. By determining the effects of low-dose combined HT on the breast, the proposed study will add timely and important information about the estimated balance of risks and benefits associated with low-dose HT and will help guide future research.
- Conditions
- Mammographic Density, Abnormal Mammogram
- Being tested
- CEE pill, Estradiol patch, Active Progesterone, Placebo tablet, Placebo patch
- Keywords
- mammographic density, abnormal mammogram, biopsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CEE pillDrug
Also called premarin
Conjugated equine estrogens 0.45 mg/day
Estradiol patchDrug
Also called Climara 50 mcg/day
Climara 50 mcg/day
Active ProgesteroneDrug
Prometrium (micronized progesterone USP encapsulated with peanut oil) 200 mg daily for the first 12 days of each month at bedtime
Placebo tabletOther
Placebo tablet
Placebo patchOther
placebo patch
Placebo progesteroneOther
placebo progesterone
| Study group | Role | What they receive |
|---|---|---|
| CEE pill, active progesterone | Active comparator | Conjugated equine estrogens 0.45 mg/day, placebo patch, Prometrium (micronized progesterone USP encapsulated with peanut oil) 200 mg daily for the first 12 days of each month at bedtime Receives: Drug: CEE pill; Drug: Active Progesterone; Other: Placebo patch |
| estradiol patch, active progesterone | Active comparator | Transdermal estradiol, 50 mcg/day, placebo tablet, Prometrium (micronized progesterone USP encapsulated with peanut oil) 200 mg daily for the first 12 days of each month at bedtime Receives: Drug: Estradiol patch; Drug: Active Progesterone; Other: Placebo tablet |
| placebo | Placebo comparator | Placebo tablet, placebo patch, placebo progesterone Receives: Other: Placebo tablet; Other: Placebo patch; Other: Placebo progesterone |
What is being measured
The primary outcome is the main question the study is designed to answer.
BIRADS Breast Density
Breast density prior to randomization. Frequency of the BIRADS category according to randomization status. BIRADS is a 1-4 category of breast density as assessed by a radiologist. 1= most fatty and least dense, while 4=most dense.
Measured: Baseline (Prior to Randomization)
BIRADS Breast Density
Frequency of the BIRADS category 1 year after randomization. BIRADS is a 1-4 category of breast density as assessed by a radiologist. 1= most fatty and least dense, while 4=most dense.
Measured: Year 1
BIRADS Breast Density
Frequency of the BIRADS category 3-4 years after randomization. BIRADS is a 1-4 category of breast density as assessed by a radiologist. 1= most fatty and least dense, while 4=most dense.
Measured: Latest (Year 3 of 4)
Secondary outcomes (1)
Abnormal Mammogram/Biopsy
Abnormal mammogram requiring additional imaging modality such as MRI or ultrasound, or a breast biopsy. Information obtained from mammography reports.
Measured: baseline to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2015 (estimated)
- Study startSep 2005
- Primary completionDec 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Mammographic DensityStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 517 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Kronos Longevity Research Institute, Albert Einstein College of Medicine, Columbia University, Mayo Clinic, University of California, San Francisco, University of Utah, University of Washington, Yale University
- Responsible party
- Principal investigator, Rulla Tamimi, Brigham and Women's Hospital
- Investigators
- Kathy Rexrode, MD, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02524561
- Sponsor's protocol ID
- 2009P002326
- Other IDs
- R01CA136918
- Acronym
- KEEPS MDBHAS
- Status last verified
- Jan 2017
- First submitted
- 13 Aug 2015
- Last updated
- 8 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided: We are willing to share data with collaborators if analyses are approved by the investigative team and approved by our IRB.
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- KEEPS Mammographic Density And Breast Health Ancillary Study
- ClinicalTrials.gov ID
- NCT02524561
- Acronym / sponsor ID
- KEEPS MDBHAS / 2009P002326
- Conditions
- Mammographic Density, Abnormal Mammogram
- Keywords
- mammographic density, abnormal mammogram, biopsy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 517 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Kronos Longevity Research Institute, Albert Einstein College of Medicine, Columbia University, Mayo Clinic, University of California, San Francisco, University of Utah, University of Washington, Yale University
- Study start
- Sep 2005
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 17 Aug 2015 (estimated)
- Results
- Posted 8 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Combined estrogen and progestin therapy has been shown to increase mammographic density and incidence of breast cancer in randomized trials. The investigators propose to examine the effects of now commonly used low-dose combined hormone therapy (HT) regimens on breast density, rates of abnormal mammogram, and circulating estrogens in the ongoing, already-funded Kronos Early Estrogen Prevention Study (KEEPS). KEEPS is a randomized clinical trial with a primary goal of examining the effects of low-dose transdermal versus oral estrogen combined with cyclic micronized progesterone on progression of subclinical atherosclerosis in recently menopausal women. Prior studies of low-dose HT have been of short duration and small size. By determining the effects of low-dose hormone therapy on the breast, the proposed ancillary study will add important information about the estimated balance of risks and benefits associated with low-dose HT and will help guide future research trials.
Detailed description
Despite data from clinical trials showing an increased risk of breast cancer and lack of overall benefit for primary prevention with hormone therapy (HT), there is still significant usage of HT by clinicians and women for treatment of moderate-to-severe systemic menopausal symptoms. Due to the possible increased risks with these preparations, current clinical recommendations advocate utilizing the lowest dose for the shortest possible duration, but average duration is often for 2-4 years. However, the effects of commonly used low-dose HT regimens on breast density and breast cancer risk are unknown. Recent data from intervention trials support the long standing hypothesis that hormonal effects on breast cancer risk are mediated through breast density. The Kronos Early Estrogen Prevention Study (KEEPS) is an ongoing, already- funded randomized clinical trial with a primary goal of examining the effects of 4 years of low- dose transdermal versus oral estrogen combined with cyclic micronized progesterone on progression of subclinical atherosclerosis in recently menopausal women. The proposed ancillary study will efficiently examine the effects of randomized low-dose HT on key breast cancer surrogate endpoints: mammographic density and rates of abnormal mammograms. In the parent KEEPS study, a total of 720 women were randomized to oral conjugated equine estrogens (0.45 mg/d), transdermal 17-beta estradiol (50 mcg/d), or placebo, with cyclic micronized progesterone (200 mg for 12 days) for active hormonal therapy groups. All participants were required to have mammography prior to study entry as well as yearly during follow-up; blood samples also were collected at these time points. Randomization was completed in 2008. In this ancillary study, we aimed to collect mammograms from eligible women consenting to be part of the ancillary study(n=517) from baseline, year 1 and year 3 will be obtained and processed centrally to calculate mammographic density. The investigators will determine if these two low-dose HT regimens are associated with change in mammographic density. The investigators will also examine if baseline mammographic density or circulating biomarkers including estradiol, estrone, and estrone sulfate, modify or mediate changes in breast density with HT. In addition, the effects of hormonal regimens on the rates of abnormal mammogram and biopsy will be determined. By determining the effects of low-dose combined HT on the breast, the proposed study will add timely and important information about the estimated balance of risks and benefits associated with low-dose HT and will help guide future research.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| CEE pill, active progesterone | Active comparator | Drug: CEE pill, Drug: Active Progesterone, Other: Placebo patchConjugated equine estrogens 0.45 mg/day, placebo patch, Prometrium (micronized progesterone USP encapsulated with peanut oil) 200 mg daily for the first 12 days of each month at bedtime |
| estradiol patch, active progesterone | Active comparator | Drug: Estradiol patch, Drug: Active Progesterone, Other: Placebo tabletTransdermal estradiol, 50 mcg/day, placebo tablet, Prometrium (micronized progesterone USP encapsulated with peanut oil) 200 mg daily for the first 12 days of each month at bedtime |
| placebo | Placebo comparator | Other: Placebo tablet, Other: Placebo patch, Other: Placebo progesteronePlacebo tablet, placebo patch, placebo progesterone |
Who may qualify
- Ages
- 42 to 58 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Women were 42-58 years of age, have had cessation of menses at or after age 40 and no menses for a minimum of 6 and a maximum of 36 months at screening.
- Subjects may or may not have had current vasomotor estrogen deficiency symptoms, had not taken estrogen- or progestogen-containing medication (oral contraceptive or hormone replacement) within 3 months of randomization, and had plasma FSH levels measured at ≥35 ng/ml and plasma E2 levels of <40 pg/ml.
Key exclusion criteria (1 listed)
- Subjects were excluded for increased endometrial thickness on ultrasound >5 mm, unless endometrial biopsy was negative; for LDL ≥ 190 mg/dl or triglycerides ≥ 400 at screening, or use of lipid lowering drugs.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CEE pillAlso: premarinConjugated equine estrogens 0.45 mg/day | Drug | CEE pill, active progesterone |
| Estradiol patchAlso: Climara 50 mcg/dayClimara 50 mcg/day | Drug | estradiol patch, active progesterone |
| Active ProgesteronePrometrium (micronized progesterone USP encapsulated with peanut oil) 200 mg daily for the first 12 days of each month at bedtime | Drug | CEE pill, active progesterone, estradiol patch, active progesterone |
| Placebo tabletPlacebo tablet | Other | estradiol patch, active progesterone, placebo |
| Placebo patchplacebo patch | Other | CEE pill, active progesterone, placebo |
| Placebo progesteroneplacebo progesterone | Other | placebo |
Primary outcome
BIRADS Breast Density
Time frame: Baseline (Prior to Randomization)
Breast density prior to randomization. Frequency of the BIRADS category according to randomization status. BIRADS is a 1-4 category of breast density as assessed by a radiologist. 1= most fatty and least dense, while 4=most dense.
BIRADS Breast Density
Time frame: Year 1
Frequency of the BIRADS category 1 year after randomization. BIRADS is a 1-4 category of breast density as assessed by a radiologist. 1= most fatty and least dense, while 4=most dense.
BIRADS Breast Density
Time frame: Latest (Year 3 of 4)
Frequency of the BIRADS category 3-4 years after randomization. BIRADS is a 1-4 category of breast density as assessed by a radiologist. 1= most fatty and least dense, while 4=most dense.
1 secondary outcome
Abnormal Mammogram/Biopsy
Time frame: baseline to 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided. We are willing to share data with collaborators if analyses are approved by the investigative team and approved by our IRB.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kathy Rexrode, MD principal investigator
Brigham and Women's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing CEE pill, Estradiol patch and Active Progesterone in people with Mammographic Density and Abnormal Mammogram, run by Brigham and Women's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
BIRADS Breast Density (time frame: Baseline (Prior to Randomization)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2017.