LOW BIOLOGIC AGGRESSIVENESS IN BREAST-CANCER IN WOMEN USING HORMONE REPLACEMENT THERAPY

Purpose: Hormone replacement therapy (HRT) has been associated with an increased risk for breast cancer. Cancers in women who use HRT are of ten less advanced, and lower mortality has been reported in those who use HRT than in nonusers, We sought to explain this by a comparison of indicators of tumor aggressiveness in patients who received HRT with those in patients who did not. Patients and Methods: A population-base d cohort of 477 postmenopausal women with breast cancer were interview ed for the use, type, and duration of HRT, Clinical variables and indi cators of tumor aggressiveness (histologic grade, hormone receptors, D NA ploidy, S-phase fraction, and c-erbB-2 oncoprotein overexpression) were analyzed. Results: Breast tumors from HRT users were smaller (odd s ratio, 0.47; P = .005), had better histologic differentiation (P = . 04), and had a lower proliferation rate (S-phase fraction, P = .009) t han tumors from nonusers. These differences persisted after adjustment s for age and method of diagnosis (mammography screening v self-referr al) by multiple logistic regression. No significant differences were o bserved in the estrogen (ER) or progesterone receptor content, c-erbB- 2 oncogene overexpression, or axillary node involvement, A subgroup an alysis showed that the tumor proliferation rates among HRT users were significantly lower only if HRT had been used at the time of diagnosis (P = .001). The type of HRT (estrogen v combination of estrogen and p rogesterone) was not associated with any clinical parameter or tumor p henotype. The association of HRT with lower proliferation rate and sma ller tumor size was exclusively caused by ER-positive tumors (P = .000 1 and P = .0035 v P > .1. respectively). Conclusion: The results indic ate that breast cancer in women who receive HRT is biologically less a ggressive than those without previous HRT, The lower cell-proliferatio n rate and smaller tumor size found in ER-positive tumors from current HRT users suggest a direct ER-mediated growth inhibitory effect of HR T on established breast tumors. This may at least partly explain why b reast cancer in HRT users has a more favorable clinical course. J Clin Oncol 16:3115-3120. (C) 1998 by American Society of Clinical Oncology .