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Melody A. Cobleigh, MD; Frances E. Norlock, DO, MPH; Denise M. Oleske, PhD; Alexander Starr, MD

JAMA. 1999;281:1528-1530.

Context  Prolonged postmenopausal hormone replacement therapy (HRT) is associated with increased incidence of breast cancer and, paradoxically, reduced breast cancer mortality. The biological rationale for this discrepancy has not been explored.

Objective  To compare the prognostic characteristics of cancers arising in women who have used HRT with those in women who never have used HRT.

Design  Prospective cohort study from December 1989 to November 1996.

Setting  Teaching hospital in a large midwestern metropolitan area.

Patients  Cohort of 331 postmenopausal women who presented consecutively with 349 invasive breast cancers.

Main Outcome Measures  Estrogen receptor (ER) status (ER positive vs ER negative) and S phase (low vs high) for current HRT users vs never users.

Results  The frequency of high S-phase fraction among cancers in women who were using HRT was markedly increased compared with that in women who had never used HRT (adjusted odds ratio [OR], 2.82; 95% confidence interval [CI], 1.04-7.66). However, the greater frequency of high S-phase fraction was limited to women with ER-positive cancers (for HRT users vs never users, OR, 5.25; 95% CI, 1.36-20.28; for ER-negative cancers in HRT users vs never users, OR, 1.08; 95% CI, 0.20-5.86).

Conclusions  Use of HRT appears to stimulate growth of ER-positive but not ER-negative breast cancer as measured by S-phase fraction. The prognostic significance of high S-phase fraction in current HRT users who have ER-positive tumors is unknown.

Author Affiliations: Section of Medical Oncology (Dr Cobleigh) and Departments of Medicine (Drs Norlock and Starr), and Preventive Medicine (Dr Oleske), Rush-Presbyterian-St Luke's Medical Center, Chicago, Ill.

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