KEEPS Mammographic Density And Breast Health Ancillary Study
Ключови думи
Резюме
Описание
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.
Дати
Последна проверка: | 12/31/2016 |
Първо изпратено: | 08/12/2015 |
Очаквано записване подадено: | 08/13/2015 |
Първо публикувано: | 08/16/2015 |
Изпратена последна актуализация: | 01/17/2017 |
Последна актуализация публикувана: | 03/07/2017 |
Дата на първите подадени резултати: | 09/19/2016 |
Дата на първите подадени резултати от QC: | 01/17/2017 |
Дата на първите публикувани резултати: | 03/07/2017 |
Действителна начална дата на проучването: | 08/31/2005 |
Приблизителна дата на първично завършване: | 11/30/2013 |
Очаквана дата на завършване на проучването: | 11/30/2013 |
Състояние или заболяване
Интервенция / лечение
Drug: CEE pill, active progesterone
Drug: estradiol patch, active progesterone
Drug: Active Progesterone
Other: Placebo tablet
Other: Placebo patch
Other: placebo
Фаза
Групи за ръце
Arm | Интервенция / лечение |
---|---|
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, active progesterone Conjugated equine estrogens 0.45 mg/day |
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, active progesterone Climara 50 mcg/day |
Placebo Comparator: placebo Placebo tablet, placebo patch, placebo progesterone | Other: placebo placebo progesterone |
Критерии за допустимост
Възрасти, отговарящи на условията за проучване | 42 Years Да се 42 Years |
Полове, допустими за проучване | Female |
Приема здрави доброволци | Да |
Критерии | 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. |
Резултат
Първични изходни мерки
1. BIRADS Breast Density [Baseline (Prior to Randomization)]
2. BIRADS Breast Density [Year 1]
3. BIRADS Breast Density [Latest (Year 3 of 4)]
Вторични изходни мерки
1. Abnormal Mammogram/Biopsy [baseline to 3 years]