Prior hormone therapy and breast cancer risk in the Women's Health Initiative randomized trial of estrogen plus progestin

Anderson, Garnet L.; Chlebowski, Rowan T.; Rossouw, Jacques E.; Rodabough, Rebecca J.; McTiernan, Anne; Margolis, Karen L.; Aggerwal, Anita; Curb, J. David; Hendrix, Susan L.; Hubbell, F. Allan; Khandekar, Jamardan; Lane, Dorothy S.; Lasser, Norman; Lopez, Ana Maria; Potter, JoNell; Ritenbaugh, Cheryl

doi:10.1016/j.maturitas.2006.05.004

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Volume 55, Issue 2 , Pages 103-115, 20 September 2006

Prior hormone therapy and breast cancer risk in the Women's Health Initiative randomized trial of estrogen plus progestin

Garnet L. Anderson
- WHI Clinical Coordinating Center, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, M3-A410, P.O. Box 19024, Seattle, WA 98109-1024, United States
- Corresponding author. Tel.: +1 206 667 4699; fax: +1 206 667 4142.
Rowan T. Chlebowski
- Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (LABioMed), Torrance, CA, United States
Jacques E. Rossouw
- NHLBI-WHI, Rockville, MD, United States
Rebecca J. Rodabough
- WHI Clinical Coordinating Center, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, M3-A410, P.O. Box 19024, Seattle, WA 98109-1024, United States
Anne McTiernan
- WHI Clinical Coordinating Center, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, M3-A410, P.O. Box 19024, Seattle, WA 98109-1024, United States
Karen L. Margolis
- Berman Center for Clinical Research, Hennepin County Medical Center, Minneapolis, MN, United States
Anita Aggerwal
- Washington Hospital Center, Washington, DC, United States
J. David Curb
- Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, United States
Susan L. Hendrix
- Department of Obstetrics and Gynecology, Wayne State University School of Medicine/Hutzel Women's Hospital, Detroit, MI, United States
F. Allan Hubbell
- Department of Medicine, University of California, Irvine, CA, United States
Jamardan Khandekar
- Department of Medicine, Northwestern University, Evanston, IL, United States
Dorothy S. Lane
- State University of New York at Stony Brook, NY, United States
Norman Lasser
- University of Medicine and Dentistry of New Jersey, Newark, NJ, United States
Ana Maria Lopez
- University of Arizona, Tucson, AZ, United States
JoNell Potter
- University of Miami, Miami, FL, United States
Cheryl Ritenbaugh
- University of Arizona, Tucson, AZ, United States

Received 23 November 2005; received in revised form 28 April 2006; accepted 5 May 2006. published online 03 July 2006.

Abstract

Objectives

To assess the extent to which prior hormone therapy modifies the breast cancer risk found with estrogen plus progestin (E+P) in the Women's Health Initiative (WHI) randomized trial.

Methods

Subgroup analyses of prior hormone use on invasive breast cancer incidence in 16,608 postmenopausal women in the WHI randomized trial of E+P over an average 5.6 years of follow-up.

Results

Small but statistically significant differences were found between prior HT users and non-users for most breast cancer risk factors but Gail risk scores were similar. Duration of E+P use within the trial (mean 4.4 years, S.D. 2.0) did not vary by prior use. Among 4311 prior users, the adjusted hazard ratio (HR) for E+P versus placebo was 1.96 (95% confidence interval [CI]: 1.17–3.27), significantly different (p=0.03) from that among 12,297 never users (HR 1.02; 95% CI: 0.77–1.36). The interaction between study arm and follow-up time was significant overall (p=0.01) and among never users (p=0.02) but not among prior users (p=0.10). The cumulative incidence over time for the E+P and placebo groups appeared to cross after about 3 years in prior users, and after about 5 years in women with no prior use. No interaction was found with duration (p=0.08) or recency of prior use (p=0.17). Prior hormone use significantly increased the E+P hazard ratio for larger, more advanced tumors.

Conclusion

A safe interval for combined hormone use could not be reliably defined with these data. However, the significant increase in breast cancer risk in the trial overall after only 5.6 years of follow-up, initially concentrated in women with prior hormone exposure, but with increasing risk over time in women without prior exposure, suggests that durations only slightly longer than those in the WHI trial are associated with increased risk of breast cancer. Longer-term exposure and follow-up data are needed.

Keywords: Estrogen, Progestin, Breast neoplasms, Subgroup analyses, Randomized trials