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Trial record 2 of 2990 for:    KEEPS

KEEPS Mammographic Density And Breast Health Ancillary Study (KEEPS MDBHAS)

This study has been completed.
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Kronos Longevity Research Institute
Albert Einstein College of Medicine, Inc.
Columbia University
Mayo Clinic
University of California, San Francisco
University of Utah
University of Washington
Yale University
Information provided by (Responsible Party):
Rulla Tamimi, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT02524561
First received: August 13, 2015
Last updated: January 18, 2017
Last verified: January 2017
  Purpose
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.

Condition Intervention
Mammographic Density Abnormal Mammogram Drug: CEE pill Drug: Estradiol patch Drug: Active Progesterone Other: Placebo tablet Other: Placebo patch Other: Placebo progesterone

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Investigator
Primary Purpose: Other
Official Title: KEEPS Mammographic Density And Breast Health Ancillary Study

Resource links provided by NLM:


Further study details as provided by Rulla Tamimi, Brigham and Women's Hospital:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 517
Study Start Date: September 2005
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: CEE pill
Conjugated equine estrogens 0.45 mg/day
Other Name: premarin
Drug: Active Progesterone
Prometrium (micronized progesterone USP encapsulated with peanut oil) 200 mg daily for the first 12 days of each month at bedtime
Other: Placebo patch
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
Drug: Estradiol patch
Climara 50 mcg/day
Other Name: Climara 50 mcg/day
Drug: Active Progesterone
Prometrium (micronized progesterone USP encapsulated with peanut oil) 200 mg daily for the first 12 days of each month at bedtime
Other: Placebo tablet
Placebo tablet
Placebo Comparator: placebo
Placebo tablet, placebo patch, placebo progesterone
Other: Placebo tablet
Placebo tablet
Other: Placebo patch
placebo patch
Other: Placebo progesterone
placebo progesterone

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.
  Eligibility

Ages Eligible for Study:   42 Years to 58 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02524561

Locations
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Brigham and Women's Hospital
National Cancer Institute (NCI)
Kronos Longevity Research Institute
Albert Einstein College of Medicine, Inc.
Columbia University
Mayo Clinic
University of California, San Francisco
University of Utah
University of Washington
Yale University
Investigators
Principal Investigator: Kathy Rexrode, MD Brigham and Women's Hospital
  More Information

Responsible Party: Rulla Tamimi, Associate Professor of Medicine, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT02524561     History of Changes
Other Study ID Numbers: 2009P002326
R01CA136918 ( U.S. NIH Grant/Contract )
Study First Received: August 13, 2015
Results First Received: September 20, 2016
Last Updated: January 18, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: We are willing to share data with collaborators if analyses are approved by the investigative team and approved by our IRB.

Keywords provided by Rulla Tamimi, Brigham and Women's Hospital:
mammographic density
abnormal mammogram
biopsy

Additional relevant MeSH terms:
Estradiol
Polyestradiol phosphate
Estrogens, Conjugated (USP)
Progesterone
Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Estradiol valerate
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Female
Progestins

ClinicalTrials.gov processed this record on July 25, 2017