Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02524561
Other study ID # 2009P002326
Secondary ID R01CA136918
Status Completed
Phase N/A
First received August 13, 2015
Last updated August 14, 2015
Start date September 2005
Est. completion date December 2013

Study information

Verified date August 2015
Source Brigham and Women's Hospital
Contact n/a
Is FDA regulated No
Health authority United States: Institutional Review Board
Study type Interventional

Clinical Trial Summary

Combined estrogen and progestin therapy has been shown to increase mammographic density and incidence of breast cancer in randomized trials. We 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.


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 KEEPS, 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, digital mammograms (available on 510 participants) from baseline, year 1 and year 3 will be obtained and processed centrally to calculate mammographic density. We will determine if these two low-dose HT regimens are associated with change in mammographic density. We 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.


Recruitment information / eligibility

Status Completed
Enrollment 727
Est. completion date December 2013
Est. primary completion date December 2013
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Female
Age group 42 Years to 58 Years
Eligibility 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 Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator)


Related Conditions & MeSH terms


Intervention

Drug:
CEE pill
Conjugated equine estrogens 0.45 mg/day
Estradiol patch
Climara 50 mcg/day
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 patch
placebo patch
Placebo progesterone
placebo progesterone

Locations

Country Name City State
United States Brigham and Women's Hospital Boston Massachusetts

Sponsors (10)

Lead Sponsor Collaborator
Brigham and Women's Hospital Albert Einstein College of Medicine of Yeshiva University, Columbia University, Kronos Longevity Research Institute, Mayo Clinic, National Cancer Institute (NCI), University of California, San Francisco, University of Utah, University of Washington, Yale University

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary mammographic density We will evaluate change from baseline to year 1, and also change from baseline to year 3 change from baseline to 3 years No
Secondary abnormal mammogram/biopsy The effects of hormonal regimens on the rates of abnormal mammogram and biopsy will be determined baseline to 3 years No
See also
  Status Clinical Trial Phase
Enrolling by invitation NCT03686098 - The Malaysian Soy and Mammographic Density Study N/A
Completed NCT04096469 - Impact of Diet and Physical Activity Changes on Body Weight, Biomarkers and Quality of Life in Breast Cancer Survivors N/A
Completed NCT04079517 - Karolinska Interventional Study of Mammograhic Density (Karisma-1) Phase 1/Phase 2
Completed NCT03629717 - RANKL Inhibition and Breast Tissue Biomarkers Early Phase 1
Completed NCT03264651 - Enobosarm and Anastrozole in Pre-menopausal Women With High Mammographic Breast Density Phase 1
Not yet recruiting NCT03696147 - Diffusion Magnetic Resonance Imaging in Mamographically Detected Asymmetric Densities
Completed NCT03314298 - A Single Dose Trial to Evaluate the Pharmacokinetics of Testosterone and Anastrozole Phase 1