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J Natl Cancer Inst. 2017 Sep 1;109(9). doi: 10.1093/jnci/djx001.

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

Author information

1
Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
2
Cancer Registry of Norway, Institute of Population Based Cancer Research, Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway and Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA.
3
University of North Carolina, Chapel Hill, NC, USA.
4
The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
5
Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA, USA.
6
National Institutes of Health, Bethesda, MD, USA.
7
Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
8
Ontario Cancer Institute, Toronto, Ontario, Canada.
9
Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
10
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
11
Stony Brook School of Medicine, Stony Brook, NY, USA.
12
Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
13
University at Buffalo, State University of New York, Buffalo, NY, USA.

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.

PMID:
28376149
PMCID:
PMC6059178
DOI:
10.1093/jnci/djx001
[Indexed for MEDLINE]
Free PMC Article

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