Clinical trial NCT02524561: KEEPS Mammographic Density And Breast Health Ancillary Study
Official title: KEEPS Mammographic Density And Breast Health Ancillary Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Mammographic Density
Abnormal Mammogram
Keywords: mammographic density
abnormal mammogram
biopsy
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Kronos Longevity Research Institute
name: Albert Einstein College of Medicine
name: Columbia University
name: Mayo Clinic
name: University of California, San Francisco
name: University of Utah
name: University of Washington
name: Yale University
First posted: 2015-08-17
Enrollment: 517
Sex: FEMALE
Minimum age (years): 42
Maximum age (years): 58
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief 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.

Eligibility 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.

Primary outcomes:
measure: BIRADS Breast Density
timeFrame: Baseline (Prior to Randomization)
measure: BIRADS Breast Density
timeFrame: Year 1
measure: BIRADS Breast Density
timeFrame: Latest (Year 3 of 4)
Secondary outcomes:
measure: Abnormal Mammogram/Biopsy
timeFrame: baseline to 3 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Kathy Rexrode, MD
role: PRINCIPAL_INVESTIGATOR
References: