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1. Hormone Therapy Suspension and Mammography in the Women's Health Initiative Clinical Trials

   • Rowan T Chlebowski, MD, PhD
   • Marcia L. Stefanick

   Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center

   The Women’s Health Initiative (WHI) randomized clinical trials evaluating hormonal therapy have previously published findings which address and expand those recently published by Buist and colleagues (1). In the WHI clinical trial evaluating estrogen plus progestin, 16,608 postmenopausal women were randomized to receive combined hormone therapy or placebo. When the trial intervention was ended, women were informed by letter to stop study pills that day and almost all did. Women in the combined estrogen plus progestin group had significantly more mammograms requiring a physician-directed intervention (short interval follow-up suggested, suspicious abnormalities, and those highly suggestive of malignancy) during the intervention (2) and throughout first post-intervention year but not thereafter (P=0.005) (3) Thus, somewhat over one year is required for improvement in mammography performance after stopping combined estrogen plus progestin use.

   In an ancillary study in the same WHI clinical trial, the association between combined estrogen plus progestin use and mammographic density was examined in a randomly identified sub-sample of trial participants. In this randomized population of 1,413 postmenopausal women, there was a statistically significant 6.0% increase in density after 1 year and a 4.9% increase at 2 years with estrogen plus progestin use findings (4) The magnitude of the increase in breast density was somewhat higher than in the cited PEPI trial. Taken together, the PEPI and WHI findings suggest that changes in breast density associated with combined hormone therapy use are substantially greater in magnitude than those observed during a menstrual cycle.

   Finally, in the WHI randomized clinical trial evaluating estrogen alone in postmenopausal women with prior hysterectomy which randomized 10,739 participants, mammograms suspicious or highly suggestive of malignancy were not increased in the estrogen alone hormone groups (5) a finding which was different from that reported in the WHI combined hormone therapy trial where an increase in abnormal mammograms was seen with estrogen plus progestin (2). Thus, differences in mammography recall rates between women receiving estrogen alone compared to combined estrogen plus progestin use would be anticipated. Awareness of these findings from the WHI randomized trials should put those of Buist and colleagues in a more complete clinical context.

   References:

   1. Buist DSM, Anderson ML, Reed SD, et al. Short-term hormone therapy suspension and mammography recall. A randomized trial. Ann Intern Med 2009;150:752-765.

   2. Chlebowski RT, Hendrix SL, Langer RD, et al. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women’s Health Initiative randomized trial. JAMA 2003;289:3243 -53.

   3. Chlebowski RT, Anderson GL, Petinger M, et al. Estrogen plus progestin and breast cancer detection by means of mammography and breast biopsy. Arch Intern Med 2008;168:370-7.

   4. McTiernan A, Martin C, Peck J, et al. Estrogen and progestin influence on mammogram density in healthy postmenopausal women in the Women’s Health Initiative Randomized Trial. J Natl Cancer Inst. 97(8):684 -91, 2005.

   5. Stefanick ML, Anderson GL, Margolis KL, et al. Effects of conjugated equine estrogens on breast cancer and mammography in postmenopausal women with hysterectomy: The Women’s Health Initiative randomized trial JAMA 242:1048-63, 2006.

   Conflict of Interest:

   None declared

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   Published June 30, 2009