AS36 – Menopausal hormone therapy and changes in mammographic density

This page provides study documentation for AS36.  The AS36 datasets are also available on this site for qualified investigators (sign in and a completed Data Distribution Agreement are required; see details on the Data site).

Investigator Names and Contact Information

Anne McTiernan, MD, PhD. - Principal Investigator*
Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA
E-mail: amctiern@fhcrc.org

* Originally, the principal investigator was Barbara S. Hulka, University of North Carolina.

Introduction/Intent

To test assess the effect of the WHI menopausal hormone trials (HT) on mammographic density. 

Materials/Methods

Data: Longitudinal mammographic breast density measurements of WHI HT participants in the estrogen-plus-progestin trial (n=413) and estrogen-alone trial (n=435).  Data consists of a baseline pre-randomization measurement, and in most instances, two follow-up measurements collected one and two years after randomization.  Participants were identified from 17 of 40 WHI clinically centers that agreed to participate, and consisted of a stratified (race/ethnicity) random sample.

Methods: Films were digitized on a Lumisys 85 laser digitizer and the files were converted to bitmap format and then assessed by a computer-assisted interactive thresholding technique to compute the percent mammographic density (ratio of dense breast area to total breast area). Two trained investigators, blind to treatment arm and sequence, performed density measurements on all films, with high reliability (intra-class correlation coefficients > 0.92). The percent density for each film is the mean of both investigators' measures for that film.  Detailed have been previously published (McTiernan 2005).

Usage notes:  The AS36 and AS178 data were intended to stand-alone.  Researchers who wish to combine MD measurements should consider a calibration model to standardize MD measurements between studies, because different computer-assisted interactive thresholding techniques were used.  Per design, there are many participants (n=266) with MD measurements from both studies; see   https://www.whi.org/researchers/data/Documents/Specimen%20Results%20Read%20Me.pdf for commentary on calibration. 

Main results and publications

Both HT preparations significantly increased mammographic density at year 1, and these effects were sustained through year 2.  Compared to estrogen-plus-progestin, the increase in mammographic density due to estrogen-alone were modest. 

Ms285 - McTiernan, Anne, et al. "Estrogen-plus-progestin use and mammographic density in postmenopausal women: women's health initiative randomized trial." Journal of the National Cancer Institute 97.18 (2005): 1366-1376.

Ms358 - McTiernan, Anne, et al. "Conjugated equine estrogen influence on mammographic density in postmenopausal women in a substudy of the women's health initiative randomized trial." Journal of Clinical Oncology 27.36 (2009): 6135-6143.

Additional publications

Ms694- Bertone-Johnson, Elizabeth R., et al. "Dietary vitamin D and calcium intake and mammographic density in postmenopausal women." Menopause (New York, NY) 17.6 (2010): 1152.

Ms1063- Bertone-Johnson, Elizabeth R., et al. "Vitamin D and calcium supplementation and one-year change in mammographic density in the women's health initiative calcium and vitamin D trial." Cancer Epidemiology Biomarkers & Prevention 21.3 (2012): 462-473.

Ms1447- Crandall, Carolyn J., et al. "Breast tenderness after initiation of conjugated equine estrogens and mammographic density change." Breast cancer research and treatment 131.3 (2012): 969-979.

For a complete, up-to-date list of WHI papers related to this ancillary study, please use the searchable Bibliography section of this website. To search for papers by study number, access the Simple Search, and enter the study number in the “Related Studies” field.