KEEPS Mammographic Density And Breast Health Ancillary Study

Mammographic Density Clinical Trial

— KEEPS MDBHAS  

Official title:

KEEPS Mammographic Density And Breast Health Ancillary Study

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

• Abnormal Mammogram
• Breast Neoplasms
• Mammographic Density

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