TY - JOUR
T1 - Mammographic Density Change With Estrogen and Progestin Therapy and Breast Cancer Risk
AU - Byrne, Celia
AU - Ursin, Giske
AU - Martin, Christopher F.
AU - Peck, Jennifer D.
AU - Cole, Elodia B.
AU - Zeng, Donglin
AU - Kim, Eunhee
AU - Yaffe, Martin D.
AU - Boyd, Norman F.
AU - Heiss, Gerardo
AU - McTiernan, Anne
AU - Chlebowski, Rowan T.
AU - Lane, Dorothy S.
AU - Manson, Jo Ann E.
AU - Wactawski-Wende, Jean
AU - Pisano, Etta D.
N1 - Funding Information:
This study was supported by the National Cancer Institute at the National Institutes of Health R01 CA105007 (EDP); the Mammogram Density Ancillary Study was funded by the National Cancer Institute at the National Institutes of Health R01 CA76017 (GH); the Women's Health Initiative program was funded by the National Heart, Lung, and Blood Institute at the National Institutes of Health, US Department of Health and Human Services, through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HSN268201100003C, HHSN268201100004C, and HHSN271201100004C.
Publisher Copyright:
© 2017 Published by Oxford University Press.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85017218277&partnerID=8YFLogxK
U2 - 10.1093/jnci/djx001
DO - 10.1093/jnci/djx001
M3 - Article
C2 - 28376149
AN - SCOPUS:85017218277
SN - 0027-8874
VL - 109
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 9
M1 - djx001
ER -