358 postmenopausal women/202 assigned randomly/178 included in the final analysis: low-dose combined HT: , conventional-dose combined HT: , tibolone: , and RLX:
45–65 yrs: low-dose combined HT (mean ± SD): 54.8 y ± 5.0; conventional-dose combined HT: 56.1 y ± 3.6; tibolone: 54.9 y ± 4.7; RLX: 56.3 y ± 4.9
Volumetric breast density by a fully automated technique in full-field digital mammograms at baseline and after 12 weeks
Retrospective analysis of a phase II prospective trial
Gail 5-year risk ≥ 1.7%, or a family history of BC, or previous LCIS, ADH, DCIS
37 high risk premenopausal
43 y (35–47)
On digitized mammograms using a semiquantitative technique and using MRI T1-weighted images to determine breast MRI volume using a semiautomatic method at baseline, after 1 and 2 years, and 1 year posttreatment
Two radiologists
Previously tested in another validation study for MRIV (94.95% agreement). For mammograms: interradiologist correlation: 1 y: 0.63; 2 y: 0.62; 3 y (one year off RLX): 0.39
Effect of raloxifene (at one of two doses) and HRT on breast density
Subgroup analysis of a prospective double-blind, randomized, placebo-controlled trial
NA
619 postmenopausal women with previous hysterectomy/168 included in the final analysis: placebo (); RLX 60 mg/day (); 150 mg/day (); estrogen 0.625 mg/day ()
Mean 53 y (45–60); mean y after menopause: 6. Placebo (mean ± SD): 52.2 y ± 5.1; RLX 60 mg/day: 54.1 y ± 4.2; 150 mg/day: 53.3 y ± 4.8; estrogen: 52.1 y ± 4.6
Digital scanning and computer-assisted segmentation of mammograms at baseline and 2 years
Effect of bazedoxifene compared with raloxifene or placebo on breast density
Retrospective analysis of a phase III randomized placebo- and active-controlled trial
NA
7 609 postmenopausal women with osteoporosis/1 243 eligible for participation; 622 eligible for digitization and 442 included in the final analysis: bazedoxifene 20 mg (); bazedoxifene 40 mg (); RLX 60 mg (); placebo ()
≤62 y; mean age: 58.7 y. Mean ± SD: bazedoxifene 20 mg/day: 58.3 y ± 2.5; 40 mg/day: 58.8 y ± 2.4; RLX 60 mg/day: 58.8 y ± 2.6; placebo: 58.8 y ± 2.5
On digitized mammograms using an interactive thresholding software at baseline and at 2 years
One radiologist blinded to time sequence and treatment arm
Effect of transdermal estradiol compared with raloxifene on breast density or heterogeneity
Post hoc analysis of a prospective randomized study
NA
500 women at least 5 y postmenopausal/270 included in the final analysis: RLX 60 mg/day (); low-dose estradiol ()4
66 years (55–80) mean ± SD: RLX: 66.7 y ± 0.5; estradiol: 66.3 y ± 0.5
Visually according to BI-RADs classification, area percentage and computer-based (E2-specific) heterogeneity examination of digitized mammograms at baseline and at 2 years
One radiologist blinded to treatment
Previously tested in another validation study: intraobserver variability between baseline and 2-year assessments = 0.79 (range 0.70–0.86)
ccHT: continuous-combined HT: conjugated equine estrogen 0.625 mg/day + medroxyprogesterone acetate 2.5 mg/day. 2Conventional-dose HT = 2 mg 17 -estradiol and 1 mg norethisterone acetate, low-dose HT = 1 mg 17 -estradiol and 0.5 mg norethisterone acetate. NA: not available or not applicable. 3Values are represented as median (25th–75th percentile of interquartile range). LCIS: lobular carcinoma in situ, ADH: atypical ductal hyperplasia, and DCIS: ductal carcinoma in situ. 4Weekly patch delivering 0.014 mg estradiol/day. 5Image Mean Index (IMI): computer-assisted algorithm calculation including identification and delimitation of the same region of interest for each image and the differentiation of gray levels into 10 classes. 6Wolfe classification: N1: parenchymal pattern composed almost entirely of fat with trabeculae but no visible ducts, P1: pattern composed mainly of fat with fibroglandular tissue that constitutes 25% of the breast, P2: pattern composed of fibroglandular tissue appearing as a heterogeneously dense breast that occupies more than 25% of the breast, and DY: extremely dense tissue. 7Tibolone versus controls: or RLX versus controls: .