- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02524561
KEEPS Mammographic Density And Breast Health Ancillary Study (KEEPS MDBHAS)
January 18, 2017 updated by: Rulla Tamimi, Brigham and Women's Hospital
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.
Study Overview
Status
Completed
Conditions
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 Type
Interventional
Enrollment (Actual)
517
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02115
- Brigham and Women's Hospital
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
42 years to 58 years (Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
Female
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: CEE pill, active progesterone
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
|
Conjugated equine estrogens 0.45 mg/day
Other Names:
Prometrium (micronized progesterone USP encapsulated with peanut oil) 200 mg daily for the first 12 days of each month at bedtime
placebo patch
|
Active Comparator: estradiol patch, active progesterone
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
|
Prometrium (micronized progesterone USP encapsulated with peanut oil) 200 mg daily for the first 12 days of each month at bedtime
Climara 50 mcg/day
Other Names:
Placebo tablet
|
Placebo Comparator: placebo
Placebo tablet, placebo patch, placebo progesterone
|
placebo patch
Placebo tablet
placebo progesterone
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Baseline (Prior to Randomization)
|
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.
|
Year 1
|
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.
|
Latest (Year 3 of 4)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Abnormal Mammogram/Biopsy
Time Frame: baseline to 3 years
|
Abnormal mammogram requiring additional imaging modality such as MRI or ultrasound, or a breast biopsy.
Information obtained from mammography reports.
|
baseline to 3 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Kathy Rexrode, MD, Brigham and Women's Hospital
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
September 1, 2005
Primary Completion (Actual)
December 1, 2013
Study Completion (Actual)
December 1, 2013
Study Registration Dates
First Submitted
August 13, 2015
First Submitted That Met QC Criteria
August 14, 2015
First Posted (Estimate)
August 17, 2015
Study Record Updates
Last Update Posted (Actual)
March 8, 2017
Last Update Submitted That Met QC Criteria
January 18, 2017
Last Verified
January 1, 2017
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2009P002326
- R01CA136918 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
UNDECIDED
IPD Plan Description
We are willing to share data with collaborators if analyses are approved by the investigative team and approved by our IRB.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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