KEEPS Mammographic Density And Breast Health Ancillary Study
Condition: Mammographic Density; Abnormal Mammogram
Study type: Interventional

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 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.
    

Intervention name(s): CEE pill; Estradiol patch; Active Progesterone; Placebo tablet; Placebo patch; Placebo progesterone
Intervention type(s): Drug; Drug; Drug; Other; Other; Other
Intervention description(s): Conjugated equine estrogens 0.45 mg/day; Climara 50 mcg/day; Prometrium (micronized progesterone USP encapsulated with peanut oil) 200 mg daily for the first 12 days of each month at bedtime; Placebo tablet; placebo patch; placebo progesterone
Other intervention name(s): premarin; Climara 50 mcg/day
Intervention MeSH terms: Estradiol; Progesterone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Other
Keywords: mammographic density; abnormal mammogram; biopsy