Abstract
Background: Postmenopausal hormone therapy cessation is associated with a decrease in mammographic density (MD), but it is unknown whether this effect is modified by woman-level characteristics. We investigated whether we could identify characteristics of women who were most likely to experience a decrease in MD due to hormone therapy cessation.
Methods: Postmenopausal hormone therapy users with a prior screening mammogram (n = 1,168) were randomized to continue hormone therapy or to suspend hormone therapy for 1 month or 2 months before their next screening mammogram. We estimated relative risks (RR) and attributable risks with 95% CIs of a ≥7.5% decrease in percentage MD (%MD) versus no change associated with hormone therapy cessation, stratified by age, body mass index (BMI), parity, and other factors.
Results: Hormone therapy cessation increased a woman's likelihood of experiencing a ≥7.5% decrease in %MD by 30% (95% CI = 1.03–1.7), but we found little evidence of effect modification by age, race, BMI, change in BMI, baseline %MD, parity, family history of breast cancer, hormone therapy type, or duration of hormone therapy use.
Conclusions: Woman-level factors do not appear to explain why some women experience a decrease in %MD following hormone therapy cessation and others do not.
Impact: We were unable to identify subgroups of women who are more likely to experience a decrease in MD due to hormone therapy cessation; other factors, such as genetic factors, may be important determinants of hormone therapy–related changes in MD. Cancer Epidemiol Biomarkers Prev; 20(10); 2309–12. ©2011 AACR.
Introduction
Mammographic density (MD) is a strong marker of breast cancer risk (1). Postmenopausal hormone therapy increases MD (2, 3), particularly combined hormone therapy (2), which also increases breast cancer risk (4). Postmenopausal hormone therapy cessation decreases MD in some women (5); reasons for this are not well understood. We examined whether the association between hormone therapy cessation and decrease in percentage MD (%MD) is modified by woman-level factors related to MD including age, race, body mass index (BMI), change in BMI between mammograms, baseline %MD, parity, and family history of breast cancer, as well as hormone therapy characteristics (type and duration of use; refs. 2, 3,5). The purpose of this study was to gain insight into the relationship between hormone therapy and mammographic density change and to identify subgroups of women whose %MD might be more likely to decrease due to hormone therapy cessation.
Methods
Methods used in the Radiological Evaluation and Breast Density (READ) randomized trial have been described previously (5). Briefly, we identified women aged 45 to 80 years who reported hormone therapy use at a screening (index) mammogram conducted at Group Health Cooperative within the past 24 months. Women due for another screening (study) mammogram who had filled 2 or more hormone therapy prescriptions in the 6 months before recruitment were eligible. Of those who completed the study mammogram (n = 1,471), we excluded women with a baseline %MD of less than 10% (n = 290), as well as women missing information on BMI (n = 13). Study methods were approved by the Institutional Review Boards of Group Health and the U.S. Department of Defense.
Women randomized to 1 month or 2 months of hormone therapy cessation were considered “exposed” (n = 738) and those randomized to continue hormone therapy were “unexposed” (n = 430). We gathered data on potential effect modifiers (age, race, BMI, change in BMI between mammograms, baseline %MD, parity, and family history of breast cancer, hormone therapy type, duration of hormone therapy use) from automated databases and study questionnaires (5). We defined change in BMI between mammograms as a change of 1.5 units or more (kg/m2), corresponding to a weight change of approximately 7 to 11 pounds for height 4′11′ to 6′0′. Buist and colleagues used Cumulus software to measure dense area and total breast area in digitized left breast craniocaudal projections; %MD was calculated as dense area divided by total area (5).
We report median change in %MD between mammograms with 95% CIs by woman-level characteristics, separately by exposure status. We used generalized linear models (GLM) with a log link and a robust variance estimator to estimate relative risks (RR) of decreasing %MD versus no change associated with hormone therapy cessation (see definitions of change below). We used GLM with an identity link to estimate attributable risks (AR). We report RRs and ARs with 95% CIs by subgroup of each potential effect modifier to assess whether certain women were more likely to experience a decrease in %MD due to cessation. To estimate RRs and ARs, we compared women who decreased ≥7.5% MD versus women with no change (defined as an absolute change of ≤3% MD). A 7.5% decrease in %MD was approximately the median level of decrease among women whose %MD decreased (>3%) and may represent a clinically relevant level of decrease. Studies suggest that women with a given %MD have a 15% to 20% higher risk of breast cancer than women whose %MD is lower by 10% (6,7). All analyses were conducted using STATA version 11.1 (StataCorp).
Results
Women randomized to suspend hormone therapy had a greater median decrease in %MD between mammograms than continued users (−2.4% vs. −0.7%), and a greater proportion who decreased by ≥7.5% MD (21% vs. 15%; Table 1). Overall, hormone therapy cessation was associated with a 30% increased likelihood of a ≥7.5% MD decrease versus no change (RR = 1.3, 95% CI = 1.03–1.7) and an attributable risk of 9% (95% CI = 2–17). We found little evidence of effect modification by the factors studied on either a multiplicative or an additive scale (Table 2).
Continued use group . | Hormone therapy cessation group . | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
. | Median change in %MD (95% CI) . | N . | Outcome: %MD change: row percent . | Median change in %MD (95% CI) . | N . | Outcome: %MD change: row percent . | ||||||
. | . | . | Decrease . | No change ±3% . | Increase >3% . | . | . | Decrease . | No change ±3% . | Increase >3% . | ||
. | . | . | ≥7.5% . | >3% to <7.5% . | . | . | . | . | ≥7.5% . | >3% to <7.5% . | . | . |
Overall | −0.7 (−1.3 to −0.2) | 430 | 15 | 20 | 36 | 29 | −2.4 (−2.7 to −1.4) | 738 | 21 | 24 | 32 | 23 |
Age, y | ||||||||||||
45–55 | −0.6 (−1.8 to 0.5) | 116 | 17 | 17 | 35 | 30 | −3.4 (−4.4 to −2.4) | 199 | 26 | 25 | 28 | 20 |
56–65 | −0.8 (−1.8 to 0.6) | 214 | 15 | 21 | 35 | 29 | −1.7 (−2.6 to −0.7) | 381 | 18 | 24 | 32 | 25 |
66+ | −0.6 (−1.9 to 0.9) | 100 | 13 | 21 | 39 | 27 | −1.4 (−3.1 to −0.3) | 158 | 19 | 24 | 36 | 21 |
Caucasian | ||||||||||||
No | −0.2 (−3.0 to 3.1) | 31 | 16 | 16 | 32 | 35 | 0.7 (−2.2 to 3.0) | 70 | 17 | 20 | 24 | 39 |
Yes | −0.8 (−1.4 to −0.2) | 398 | 15 | 21 | 36 | 28 | −2.4 (−3.0 to −1.7) | 664 | 21 | 25 | 33 | 22 |
Baseline BMI, kg/m2 | ||||||||||||
<25 | −0.2 (−1.4 to 1.0) | 191 | 17 | 15 | 34 | 34 | −1.6 (−2.6 to −0.3) | 311 | 20 | 22 | 31 | 27 |
25–30 | −0.7 (−1.7 to −0.1) | 147 | 12 | 23 | 39 | 26 | −2.0 (−3.0 to −0.7) | 244 | 20 | 24 | 32 | 24 |
>30 | −1.4 (−3.5 to 0.05) | 92 | 17 | 25 | 35 | 23 | −3.4 (−4.4 to −2.0) | 183 | 22 | 29 | 33 | 16 |
Baseline %MD | ||||||||||||
10% to <20% | −0.3 (−1.4 to 0.6) | 137 | 4 | 21 | 50 | 26 | −0.8 (−1.8 to 0.3) | 241 | 9 | 27 | 40 | 24 |
20% to <30% | 0.2 (−1.0 to 2.0) | 119 | 12 | 19 | 34 | 35 | −1.7 (−2.5 to −0.6) | 201 | 17 | 24 | 36 | 23 |
30% to <40% | −2.6 (−4.4 to −0.1) | 87 | 25 | 23 | 26 | 25 | −3.4 (−4.8 to −2.0) | 152 | 28 | 25 | 26 | 20 |
40+% | −2.6 (−4.9 to −0.3) | 87 | 29 | 16 | 26 | 29 | −5.1 (−7.0 to −2.7) | 144 | 38 | 20 | 18 | 24 |
Parity | ||||||||||||
Parous | −0.9 (−1.5 to −0.2) | 347 | 16 | 20 | 36 | 27 | −2.3 (−2.9 to −1.5) | 583 | 21 | 25 | 32 | 23 |
Nulliparous | −0.2 (−1.1 to 1.8) | 82 | 12 | 18 | 35 | 34 | −1.5 (-3.2 to −0.3) | 153 | 20 | 24 | 33 | 24 |
Family history of breast cancer (first degree) | ||||||||||||
No | −0.4 (−0.9 to 0.2) | 330 | 16 | 18 | 36 | 30 | −2.3 (−3.0 to −1.5) | 589 | 21 | 24 | 31 | 23 |
Yes | −2.2 (−3.4 to −0.4) | 89 | 12 | 30 | 31 | 26 | −1.7 (−3.2 to −0.5) | 130 | 19 | 24 | 35 | 22 |
Change in BMI, kg/m2 | ||||||||||||
Decrease >1.5 | 1.1 (−3.4 to 4.3) | 37 | 11 | 24 | 30 | 35 | −0.9 (−3.6 to 0.2) | 64 | 16 | 23 | 38 | 23 |
No change (≤1.5) | −0.4 (−1.4 to 0.4) | 286 | 16 | 18 | 35 | 31 | −2.0 (−2.6 to −1.1) | 486 | 21 | 24 | 30 | 26 |
Increase >1.5 | −1.8 (−3.5 to −0.7) | 84 | 17 | 24 | 39 | 20 | −2.9 (−4.1 to −1.7) | 159 | 22 | 27 | 33 | 18 |
Hormone therapy type | ||||||||||||
Estrogen therapy | −0.9 (−1.7 to −0.2) | 264 | 16 | 22 | 35 | 27 | −2.1 (−2.7 to −1.1) | 450 | 19 | 25 | 33 | 23 |
Estrogen + progesterone | −0.2 (−1.4 to 0.8) | 166 | 14 | 16 | 37 | 32 | −2.4 (−3.4 to −1.2) | 288 | 24 | 24 | 30 | 23 |
Duration of prior hormone therapy use at baseline, y | ||||||||||||
<5 | 0.5 (−1.1 to −2.5) | 57 | 16 | 14 | 37 | 33 | −1.7 (−5.1 to 1.7) | 86 | 31 | 13 | 24 | 31 |
5–9 | −1.2 (−2.8 to 0.5) | 93 | 18 | 18 | 35 | 28 | −2.7 (−3.9 to −1.6) | 159 | 23 | 25 | 35 | 17 |
10–14 | −0.7 (−1.8 to 2.0) | 83 | 14 | 20 | 29 | 36 | −2.2 (−3.5 to −1.0) | 167 | 17 | 28 | 32 | 23 |
15+ | −0.9 (−1.6 to 0.2) | 173 | 14 | 22 | 38 | 25 | −2.0 (−3.1 to −0.6) | 277 | 20 | 25 | 33 | 22 |
Continued use group . | Hormone therapy cessation group . | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
. | Median change in %MD (95% CI) . | N . | Outcome: %MD change: row percent . | Median change in %MD (95% CI) . | N . | Outcome: %MD change: row percent . | ||||||
. | . | . | Decrease . | No change ±3% . | Increase >3% . | . | . | Decrease . | No change ±3% . | Increase >3% . | ||
. | . | . | ≥7.5% . | >3% to <7.5% . | . | . | . | . | ≥7.5% . | >3% to <7.5% . | . | . |
Overall | −0.7 (−1.3 to −0.2) | 430 | 15 | 20 | 36 | 29 | −2.4 (−2.7 to −1.4) | 738 | 21 | 24 | 32 | 23 |
Age, y | ||||||||||||
45–55 | −0.6 (−1.8 to 0.5) | 116 | 17 | 17 | 35 | 30 | −3.4 (−4.4 to −2.4) | 199 | 26 | 25 | 28 | 20 |
56–65 | −0.8 (−1.8 to 0.6) | 214 | 15 | 21 | 35 | 29 | −1.7 (−2.6 to −0.7) | 381 | 18 | 24 | 32 | 25 |
66+ | −0.6 (−1.9 to 0.9) | 100 | 13 | 21 | 39 | 27 | −1.4 (−3.1 to −0.3) | 158 | 19 | 24 | 36 | 21 |
Caucasian | ||||||||||||
No | −0.2 (−3.0 to 3.1) | 31 | 16 | 16 | 32 | 35 | 0.7 (−2.2 to 3.0) | 70 | 17 | 20 | 24 | 39 |
Yes | −0.8 (−1.4 to −0.2) | 398 | 15 | 21 | 36 | 28 | −2.4 (−3.0 to −1.7) | 664 | 21 | 25 | 33 | 22 |
Baseline BMI, kg/m2 | ||||||||||||
<25 | −0.2 (−1.4 to 1.0) | 191 | 17 | 15 | 34 | 34 | −1.6 (−2.6 to −0.3) | 311 | 20 | 22 | 31 | 27 |
25–30 | −0.7 (−1.7 to −0.1) | 147 | 12 | 23 | 39 | 26 | −2.0 (−3.0 to −0.7) | 244 | 20 | 24 | 32 | 24 |
>30 | −1.4 (−3.5 to 0.05) | 92 | 17 | 25 | 35 | 23 | −3.4 (−4.4 to −2.0) | 183 | 22 | 29 | 33 | 16 |
Baseline %MD | ||||||||||||
10% to <20% | −0.3 (−1.4 to 0.6) | 137 | 4 | 21 | 50 | 26 | −0.8 (−1.8 to 0.3) | 241 | 9 | 27 | 40 | 24 |
20% to <30% | 0.2 (−1.0 to 2.0) | 119 | 12 | 19 | 34 | 35 | −1.7 (−2.5 to −0.6) | 201 | 17 | 24 | 36 | 23 |
30% to <40% | −2.6 (−4.4 to −0.1) | 87 | 25 | 23 | 26 | 25 | −3.4 (−4.8 to −2.0) | 152 | 28 | 25 | 26 | 20 |
40+% | −2.6 (−4.9 to −0.3) | 87 | 29 | 16 | 26 | 29 | −5.1 (−7.0 to −2.7) | 144 | 38 | 20 | 18 | 24 |
Parity | ||||||||||||
Parous | −0.9 (−1.5 to −0.2) | 347 | 16 | 20 | 36 | 27 | −2.3 (−2.9 to −1.5) | 583 | 21 | 25 | 32 | 23 |
Nulliparous | −0.2 (−1.1 to 1.8) | 82 | 12 | 18 | 35 | 34 | −1.5 (-3.2 to −0.3) | 153 | 20 | 24 | 33 | 24 |
Family history of breast cancer (first degree) | ||||||||||||
No | −0.4 (−0.9 to 0.2) | 330 | 16 | 18 | 36 | 30 | −2.3 (−3.0 to −1.5) | 589 | 21 | 24 | 31 | 23 |
Yes | −2.2 (−3.4 to −0.4) | 89 | 12 | 30 | 31 | 26 | −1.7 (−3.2 to −0.5) | 130 | 19 | 24 | 35 | 22 |
Change in BMI, kg/m2 | ||||||||||||
Decrease >1.5 | 1.1 (−3.4 to 4.3) | 37 | 11 | 24 | 30 | 35 | −0.9 (−3.6 to 0.2) | 64 | 16 | 23 | 38 | 23 |
No change (≤1.5) | −0.4 (−1.4 to 0.4) | 286 | 16 | 18 | 35 | 31 | −2.0 (−2.6 to −1.1) | 486 | 21 | 24 | 30 | 26 |
Increase >1.5 | −1.8 (−3.5 to −0.7) | 84 | 17 | 24 | 39 | 20 | −2.9 (−4.1 to −1.7) | 159 | 22 | 27 | 33 | 18 |
Hormone therapy type | ||||||||||||
Estrogen therapy | −0.9 (−1.7 to −0.2) | 264 | 16 | 22 | 35 | 27 | −2.1 (−2.7 to −1.1) | 450 | 19 | 25 | 33 | 23 |
Estrogen + progesterone | −0.2 (−1.4 to 0.8) | 166 | 14 | 16 | 37 | 32 | −2.4 (−3.4 to −1.2) | 288 | 24 | 24 | 30 | 23 |
Duration of prior hormone therapy use at baseline, y | ||||||||||||
<5 | 0.5 (−1.1 to −2.5) | 57 | 16 | 14 | 37 | 33 | −1.7 (−5.1 to 1.7) | 86 | 31 | 13 | 24 | 31 |
5–9 | −1.2 (−2.8 to 0.5) | 93 | 18 | 18 | 35 | 28 | −2.7 (−3.9 to −1.6) | 159 | 23 | 25 | 35 | 17 |
10–14 | −0.7 (−1.8 to 2.0) | 83 | 14 | 20 | 29 | 36 | −2.2 (−3.5 to −1.0) | 167 | 17 | 28 | 32 | 23 |
15+ | −0.9 (−1.6 to 0.2) | 173 | 14 | 22 | 38 | 25 | −2.0 (−3.1 to −0.6) | 277 | 20 | 25 | 33 | 22 |
NOTE: Row percents may not add to 100 because of rounding to the nearest 1%. N's may not sum to totals due to missing values. The study had 88% power to detect a 7% change in density among exposed women, if there were no change among unexposed.
. | Continued hormone therapy use (referent group) . | 1- to 2-mo hormone therapy cessation . | 1- to 2-mo vs. no hormone therapy cessation . | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
. | No change,a n (%) . | Decrease ≥7.5%, n (%) . | No change, n (%) . | Decrease ≥7.5%, n (%) . | RRb (95% CI) . | ARb, c (%) (95% CI) . | ||||||
Overall effect | 154 (100) | 66 (100) | 235 (100) | 152 (100) | 1.3 (1.03–1.7) | 9 (2–17) | ||||||
Age, y | ||||||||||||
66+ | 39 (25) | 20 (30) | 57 (24) | 30 (20) | 1.5 (1.0–2.2) | 9 (−6 to 25) | ||||||
56–65 | 74 (48) | 33 (50) | 122 (52) | 70 (46) | 1.2 (0.8–1.7) | 6 (−5 to 17) | ||||||
45–55 | 41 (27) | 20 (30) | 56 (24) | 52 (34) | 1.4 (0.8–2.4) | 15 (0–30) | ||||||
BMI,d kg/m2 | ||||||||||||
<25 | 65 (42) | 32 (48) | 96 (41) | 54 (40) | 1.2 (0.9–1.7) | 7 (−5 to 19) | ||||||
25–30 | 57 (37) | 18 (27) | 79 (34) | 48 (32) | 1.6 (1.0–2.5) | 14 (1–27) | ||||||
>30 | 32 (21) | 16 (24) | 60 (26) | 41 (27) | 1.2 (0.8–1.9) | 7 (−9 to 24) | ||||||
Baseline %MDd | ||||||||||||
10% to <20% | 68 (44) | 5 (8) | 97 (41) | 21 (14) | 2.6 (1.02–6.6) | 11 (2–20) | ||||||
20% to <30% | 40 (26) | 14 (21) | 72 (31) | 34 (22) | 1.2 (0.7–2.1) | 6 (−9 to 21) | ||||||
30% to <40% | 23 (15) | 22 (33) | 40 (17) | 43 (28) | 1.1 (0.7–1.5) | 3 (−15 to 21) | ||||||
40+% | 23 (15) | 25 (38) | 26 (11) | 54 (36) | 1.3 (0.9–1.8) | 15 (−2 to 33) | ||||||
Parity | ||||||||||||
Parous | 125 (81) | 56 (85) | 185 (79) | 121 (80) | 1.3 (1.0–1.7) | 9 (0–17) | ||||||
Nulliparous | 29 (19) | 10 (15) | 50 (21) | 31 (20) | 1.5 (0.8–2.7) | 13 (−5 to 30) | ||||||
Family history of breast cancer (first degree) | ||||||||||||
Yes | 28 (18) | 11 (17) | 45 (19) | 25 (16) | 1.3 (0.7–2.3) | 10 (1–19) | ||||||
No | 120 (78) | 52 (79) | 185 (79) | 125 (82) | 1.3 (1.0–1.7) | 8 (−11 to 26) | ||||||
Change in BMI | ||||||||||||
Decrease >1.5 | 11 (7) | 4 (6) | 24 (10) | 10 (7) | 1.1 (0.4–3.0) | 3 (−24 to 30) | ||||||
No change (≤1.5) | 99 (64) | 46 (70) | 145 (62) | 100 (66) | 1.3 (1.0–1.7) | 9 (0–19) | ||||||
Increase >1.5 | 33 (21) | 14 (21) | 53 (23) | 35 (23) | 1.3 (0.8–2.2) | 10 (−7 to 27) | ||||||
Hormone therapy type | ||||||||||||
Estrogen therapy | 92 (60) | 42 (64) | 149 (63) | 84 (55) | 1.2 (0.8–1.6) | 5 (−5 to 15) | ||||||
Estrogen + progesterone | 62 (40) | 24 (36) | 86 (37) | 68 (45) | 1.6 (1.1–2.3) | 16 (4–29) | ||||||
Hormone therapy duration,e y | ||||||||||||
<5 | 21 (14) | 9 (14) | 21 (9) | 27 (18) | 1.9 (1.0–3.4) | 26 (5–48) | ||||||
5–9 | 33 (21) | 17 (26) | 55 (23) | 37 (24) | 1.2 (0.7–1.9) | 6 (−10 to 23) | ||||||
10–14 | 24 (16) | 12 (18) | 54 (23) | 28 (18) | 1.0 (0.6–1.8) | 1 (−18 to 19) | ||||||
15+ | 66 (43) | 25 (38) | 91 (39) | 55 (36) | 1.4 (0.9–2.0) | 10 (2–22) |
. | Continued hormone therapy use (referent group) . | 1- to 2-mo hormone therapy cessation . | 1- to 2-mo vs. no hormone therapy cessation . | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
. | No change,a n (%) . | Decrease ≥7.5%, n (%) . | No change, n (%) . | Decrease ≥7.5%, n (%) . | RRb (95% CI) . | ARb, c (%) (95% CI) . | ||||||
Overall effect | 154 (100) | 66 (100) | 235 (100) | 152 (100) | 1.3 (1.03–1.7) | 9 (2–17) | ||||||
Age, y | ||||||||||||
66+ | 39 (25) | 20 (30) | 57 (24) | 30 (20) | 1.5 (1.0–2.2) | 9 (−6 to 25) | ||||||
56–65 | 74 (48) | 33 (50) | 122 (52) | 70 (46) | 1.2 (0.8–1.7) | 6 (−5 to 17) | ||||||
45–55 | 41 (27) | 20 (30) | 56 (24) | 52 (34) | 1.4 (0.8–2.4) | 15 (0–30) | ||||||
BMI,d kg/m2 | ||||||||||||
<25 | 65 (42) | 32 (48) | 96 (41) | 54 (40) | 1.2 (0.9–1.7) | 7 (−5 to 19) | ||||||
25–30 | 57 (37) | 18 (27) | 79 (34) | 48 (32) | 1.6 (1.0–2.5) | 14 (1–27) | ||||||
>30 | 32 (21) | 16 (24) | 60 (26) | 41 (27) | 1.2 (0.8–1.9) | 7 (−9 to 24) | ||||||
Baseline %MDd | ||||||||||||
10% to <20% | 68 (44) | 5 (8) | 97 (41) | 21 (14) | 2.6 (1.02–6.6) | 11 (2–20) | ||||||
20% to <30% | 40 (26) | 14 (21) | 72 (31) | 34 (22) | 1.2 (0.7–2.1) | 6 (−9 to 21) | ||||||
30% to <40% | 23 (15) | 22 (33) | 40 (17) | 43 (28) | 1.1 (0.7–1.5) | 3 (−15 to 21) | ||||||
40+% | 23 (15) | 25 (38) | 26 (11) | 54 (36) | 1.3 (0.9–1.8) | 15 (−2 to 33) | ||||||
Parity | ||||||||||||
Parous | 125 (81) | 56 (85) | 185 (79) | 121 (80) | 1.3 (1.0–1.7) | 9 (0–17) | ||||||
Nulliparous | 29 (19) | 10 (15) | 50 (21) | 31 (20) | 1.5 (0.8–2.7) | 13 (−5 to 30) | ||||||
Family history of breast cancer (first degree) | ||||||||||||
Yes | 28 (18) | 11 (17) | 45 (19) | 25 (16) | 1.3 (0.7–2.3) | 10 (1–19) | ||||||
No | 120 (78) | 52 (79) | 185 (79) | 125 (82) | 1.3 (1.0–1.7) | 8 (−11 to 26) | ||||||
Change in BMI | ||||||||||||
Decrease >1.5 | 11 (7) | 4 (6) | 24 (10) | 10 (7) | 1.1 (0.4–3.0) | 3 (−24 to 30) | ||||||
No change (≤1.5) | 99 (64) | 46 (70) | 145 (62) | 100 (66) | 1.3 (1.0–1.7) | 9 (0–19) | ||||||
Increase >1.5 | 33 (21) | 14 (21) | 53 (23) | 35 (23) | 1.3 (0.8–2.2) | 10 (−7 to 27) | ||||||
Hormone therapy type | ||||||||||||
Estrogen therapy | 92 (60) | 42 (64) | 149 (63) | 84 (55) | 1.2 (0.8–1.6) | 5 (−5 to 15) | ||||||
Estrogen + progesterone | 62 (40) | 24 (36) | 86 (37) | 68 (45) | 1.6 (1.1–2.3) | 16 (4–29) | ||||||
Hormone therapy duration,e y | ||||||||||||
<5 | 21 (14) | 9 (14) | 21 (9) | 27 (18) | 1.9 (1.0–3.4) | 26 (5–48) | ||||||
5–9 | 33 (21) | 17 (26) | 55 (23) | 37 (24) | 1.2 (0.7–1.9) | 6 (−10 to 23) | ||||||
10–14 | 24 (16) | 12 (18) | 54 (23) | 28 (18) | 1.0 (0.6–1.8) | 1 (−18 to 19) | ||||||
15+ | 66 (43) | 25 (38) | 91 (39) | 55 (36) | 1.4 (0.9–2.0) | 10 (2–22) |
aPercentages may not add to 100 because of rounding to the nearest 1%.
bUnadjusted (assignment to the exposure was randomized and is not associated with other factors; ref. 5).
cAR: cumulative incidence (proportion) of women in the cessation group who experienced a decrease in MD of ≥7.5% due to hormone therapy cessation.
dAt index mammogram.
eDuration of prior hormone therapy use at baseline.
Discussion
We did not observe strong evidence that the effect of hormone therapy cessation on %MD varies by woman-level characteristics. Our findings suggest that hormone therapy cessation may have a similar biological effect on %MD regardless of age, BMI, baseline %MD, and the other factors we examined. Although we used continuous measures of %MD, which are more precise than commonly used categorical measures, and a single trained reader interpreted all mammograms, measurement error of %MD remains a concern. Quality control sampling indicated that less than 10% of mammography rereads differed by ≥7.5% MD. We were unable to measure %MD immediately before hormone therapy cessation. However, our comparison of 2 large, randomized groups allowed us to infer this change with reasonable confidence. Additional strengths include a large sample size, randomization of exposure, high compliance with the intervention (8), and high-quality administrative data.
Our findings suggest that hormone therapy cessation–associated decrease in %MD is not predicted by woman-level factors. Other explanations for why subsets of women experience %MD decreases due to hormone therapy cessation, such as genetic factors, should be considered.
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Acknowledgments
This study could not have been completed without the assistance of Tammy Dodd, Linda Palmer, Dawn Fitzgibbons, Deborah Seger, Susan Reed, Katherine Newton, or Melissa Rabelhofer. The authors would further like to thank members of our advisory board: Hermien Watkins, Paula Hoffman, Deb Schiro, and Margrit Schubiger; members of the Data Safety and Monitoring Board: Susan Heckbert, MD, PhD, Chair, Department of Epidemiology, University of Washington; Ben Anderson, MD, University of Washington; Mary Anne Rossing, DVM, PhD, Fred Hutchinson Cancer Research Center; Robert D. Rosenberg, MD, University of New Mexico; Thomas Lumley, PhD, University of Washington Department of Biostatistics; and Elizabeth Lin, MD, Group Health Permanente medical monitor. They also thank Robert Karl, MD, Donna White, MD, and Jo Ellen Callahan for their support for implementing this trial at Group Health; Noel Weiss, MD, MPH, and Jessica Chubak, PhD, MBHL, for providing feedback on methods and analyses; Stephen Taplin, MD, MPH, for his collaboration in getting this study funded when he was an investigator at Group Health Cooperative.
Grant Support
The READ study was funded by the Department of Defense (principal investigator, D.S.M. Buist; DAMD17-03-1-0447). Registered clinical trial number: NCT00117663. Study participants were recruited from the Group Health Breast Cancer Screening Program funded by the National Cancer Institute (principal investigator: D.S.M. Buist, U01CA63731).