Hormone replacement therapy and high S phase in breast cancer

Context Prolonged postmenopausal hormone replacement therapy (HRT) is assoc iated 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 w omen 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 wit h 349 invasive breast cancers. Main outcome Measures Estrogen receptor (ER) status (ER positive vs ER nega tive) 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 w ere using HRT was markedly increased com pared with that in women who had n ever 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 l imited 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 us ers, OR, 1.08; 95% CI, 0.20-5.86). Conclusions Use of HRT appears to stimulate growth of ER-positive but not E R-negative breast cancer as measured by S-phase fraction. The prognostic si gnificance of high S-phase fraction in current HRT users who have ER-positi ve tumors is unknown.