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Randomized Controlled Trial
. 2017 Sep 1;109(9):djx001.
doi: 10.1093/jnci/djx001.

Mammographic Density Change With Estrogen and Progestin Therapy and Breast Cancer Risk

Celia Byrne  1 , Giske Ursin  2 , Christopher F Martin  3 , Jennifer D Peck  4 , Elodia B Cole  5 , Donglin Zeng  3 , Eunhee Kim  6 , Martin D Yaffe  7 , Norman F Boyd  8 , Gerardo Heiss  3 , Anne McTiernan  9 , Rowan T Chlebowski  10 , Dorothy S Lane  11 , JoAnn E Manson  12 , Jean Wactawski-Wende  13 , Etta D Pisano  5
Affiliations
Randomized Controlled Trial

Mammographic Density Change With Estrogen and Progestin Therapy and Breast Cancer Risk

Celia Byrne et al. J Natl Cancer Inst. .

Abstract

Background: Estrogen plus progestin therapy increases both mammographic density and breast cancer incidence. Whether mammographic density change associated with estrogen plus progestin initiation predicts breast cancer risk is unknown.

Methods: We conducted an ancillary nested case-control study within the Women's Health Initiative trial that randomly assigned postmenopausal women to daily conjugated equine estrogen 0.625 mg plus medroxyprogesterone acetate 2.5 mg or placebo. Mammographic density was assessed from mammograms taken prior to and one year after random assignment for 174 women who later developed breast cancer (cases) and 733 healthy women (controls). Logistic regression analyses included adjustment for confounders and baseline mammographic density when appropriate.

Results: Among women in the estrogen plus progestin arm (97 cases/378 controls), each 1% positive change in percent mammographic density increased breast cancer risk 3% (odds ratio [OR] = 1.03, 95% confidence interval [CI] = 1.01 to 1.06). For women in the highest quintile of mammographic density change (>19.3% increase), breast cancer risk increased 3.6-fold (95% CI = 1.52 to 8.56). The effect of estrogen plus progestin use on breast cancer risk (OR = 1.28, 95% CI = 0.90 to 1.82) was eliminated in this study, after adjusting for change in mammographic density (OR = 1.00, 95% CI = 0.66 to 1.51).

Conclusions: We found the one-year change in mammographic density after estrogen plus progestin initiation predicted subsequent increase in breast cancer risk. All of the increased risk from estrogen plus progestin use was mediated through mammographic density change. Doctors should evaluate changes in mammographic density with women who initiate estrogen plus progestin therapy and discuss the breast cancer risk implications.

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Figures

Figure 1.
Figure 1.
Distribution of change in mammographic density from baseline to at least one year after random assignment within participants from the placebo arm of the Women’s Health Initiative. The mean change in percent mammographic density declined by 0.05%, with a median change in mammographic density of 0.0% and a standard deviation of 6.36.
Figure 2.
Figure 2.
Distribution of change in mammographic density from baseline to at least one year after random assignment within participants from the estrogen plus progestin arm of the Women’s Health Initiative. The mean change in percent mammographic density increased by 9.73%, with a median change in mammographic density of 6.02% and a standard deviation of 12.80.
See this image and copyright information in PMC

References

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