Review Article

Effect of Preventive Hormonal Therapy on Breast Density: A Systematic Qualitative Review

Table 5

Raloxifene (RLX n: 9) and aromatase inhibitors (Let, ANAS, and EXE n: 7) studies: results: effect on BD and confounding factors of interaction.

AuthorsChange in BDConfounding factors
Treatment Endpoint P

Jackson et al. 2003 [42]Increased BD, patients number (%)
RLX1 (0.9%)<0.001NMTA
ccHRT23 (27.4%)

Eilertsen et al. 2008 [43] Median changes in volumetric BD %
(I) Low-dose HT+17.2% (95% CI 1.1–28.7) 0.001
(II) Conventional HT+15.0% (95% CI 4.8–28.6)0.001NMTA
(III) Tibolone+0.7% (95% CI 9.2-to 7.3)0.9
(IV) Rlx–4.1% (95% CI 6.9 to 2.1)0.09

Eng-Wong et al. 2008 [44] Median % Δ MRIV Mean BMI (range) 24 (18–41) and mean age (range) 43 y (35–47) are not significantly correlated with BD at baseline, NMTA
1 year−17% (95% CI −28 to −9) 0.0017
2 years −16% (95% CI −31 to −14)0.0004
3 years −9% (95% CI −18 to 20)0.64

Freedman et al. 2001 [45] Mean change in BD % No statistically significant therapy-by-subgroup interactions (for BMI, age at entry, menopausal status, use of HRT, baseline breast density, and smoking status)
Placebo
RLX 60 mg <0.021
RLX 150 mg
Estrogen

Harvey et al. 2009 [46] Mean change in BD %(SD)
Bazedoxifene 20 mg−1.2% (4.4)
Bazedoxifene 40 mg −0.4% (3.5)NSNMTA
RLX 60 mg −0.5% (3.4)
Placebo −0.2% (3.0)

Nielsen et al. 2009 [47] Area % E2-HER 2BMI: negatively correlated with BD at baseline
NMTA
RLX+2%3+0.41<0.05 for area
Estradiol+4%+0.32<0.0001 for2

Lasco et al. [48] Image mean index (%)
RLX−1.9%<0.05NMTA
ControlsNo significant change

Christodoulakos et al. 2002 [49] Patients number (%) No change Increase Decrease NMTA
RLX36 (75)3 (6.3)9 (18)NA
Tibolone 44 (78.6) 6 (10.7)6 (10.7)
Controls20 (74.1)7 (25.9)

Cirpan et al. 2006 [50]RLXNo change in
BIRADs categories4
=0.32NMTA

Cigler et al. 2010 [51] Mean change No statistically significant therapy-by-subgroup interactions (for BMI and age at entry)
Letrozole−0.01% (95% CI −3.89 to 3.87)=0.69
Placebo−1.32% (95% CI −8.86 to 6.22)

Vachon et al. 2007 [52] Mean change No statistically significant therapy-by-subgroup interactions (for BMI and age at entry)
Letrozole−2.7%=0.96
Placebo−3.0%

Smith et al. 2012 [53] Patients number Decrease Increase 0.0358NMTA
Letrozole11/163/16

Fabian et al. 2007 [54]Mean relative change NANMTA
Letrozole + HRT50.4
(Baseline: 31.5 %; Posttreatment: 29.4 %)

Mousa et al. 2008 [55] Δ % dense IPI (SD) 6NMTA
Letrozole + HRT 0.044
HRT alone

Prowell et al. 2011 [56]
Anastrozole
Mean change 16% (95% CI: −30 to 2)0.08No statistically significant therapy-by-subgroup interactions (for BMI and age at entry)

Cigler et al. 2011 [57] Mean change No statistically significant therapy-by-subgroup interactions (for BMI and age at entry)
Exemestane−0.17 (95% CI from −4.34 to 4.00)0.37
Placebo−2.93 (95% CI from −8.70 to 2.85)

ccHRT: continuous-combined hormone therapy that consisted of conjugated equine estrogen 0.625 mg/day plus medroxyprogesterone acetate 2.5 mg/day. NMTA: no multivariable analysis of interaction with treatment effect available. ΔMRIV = change in breast MRI volume. 1The mean density within the placebo group and both raloxifene groups decreased statistically significantly from baseline ( for each group), while the mean density in the ERT (estrogen replacement therapy) group increased but not statistically significantly. 2E2-HER: computer-based (E2-specific) heterogeneity examination of radiographs. 3None of the patients in either treatment group demonstrated a decrease in breast density; using area % measurement: no significant increase from baseline. NA: not available. 4Only in one patient did the BI-RADS classification of 2 change to 3 after 12 months of therapy. 5HRT: hormonal replacement therapy. 6IPI: computerized calculation of integrated pixel intensity.