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


CONCLUSIONS
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.
Anderson
Garnet L
GL
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. garnet@whi.org <garnet@whi.org>
Chlebowski
Rowan T
RT
Rossouw
Jacques E
JE
Rodabough
Rebecca J
RJ
McTiernan
Anne
A
Margolis
Karen L
KL
Aggerwal
Anita
A
David Curb
J
J
Hendrix
Susan L
SL
Allan Hubbell
F
F
Khandekar
Jamardan
J
Lane
Dorothy S
DS
Lasser
Norman
N
Lopez
Ana Maria
AM
Potter
JoNell
J
Ritenbaugh
Cheryl
C
D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology / Q000209:etiology*; D016009:Chi-Square Distribution; D004311:Double-Blind Method; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D004966:Estrogens, Conjugated (USP) / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000009:adverse effects; D008875:Middle Aged; D012307:Risk Factors; D016387:Women's Health
D004966:Estrogens, Conjugated (USP); D017258:Medroxyprogesterone Acetate