Journal of Clinical Oncology, Vol 16, 3115-3120, Copyright © 1998 by American Society of Clinical Oncology
Low biologic aggressiveness in breast cancer in women using hormone replacement therapy
K Holli, J Isola and J Cuzick
Department of Oncology, University Hospital of Tampere, Institute of Medical Technology, University of Tampere, Finland. kaholli@tays.fi
PURPOSE: Hormone replacement therapy (HRT) has been associated with an
increased risk for breast cancer. Cancers in women who use HRT are often
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-based cohort of 477
postmenopausal women with breast cancer were interviewed for the use, type,
and duration of HRT. Clinical variables and indicators of tumor
aggressiveness (histologic grade, hormone receptors, DNA ploidy, S-phase
fraction, and c-erbB-2 oncoprotein overexpression) were analyzed. RESULTS:
Breast tumors from HRT users were smaller (odds ratio, 0.47; P=.005), had
better histologic differentiation (P=.04), and had a lower proliferation
rate (S-phase fraction, P=.009) than tumors from nonusers. These
differences persisted after adjustments for age and method of diagnosis
(mammography screening v self-referral) by multiple logistic regression. No
significant differences were observed in the estrogen (ER) or progesterone
receptor content, c-erbB-2 oncogene overexpression, or axillary node
involvement. A subgroup analysis 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 progesterone) was not associated with any clinical parameter
or tumor phenotype. The association of HRT with lower proliferation rate
and smaller tumor size was exclusively caused by ER-positive tumors
(P=.0001 and P=.0035 v P > .1, respectively). CONCLUSION: The results
indicate that breast cancer in women who receive HRT is biologically less
aggressive than those without previous HRT. The lower cell- proliferation
rate and smaller tumor size found in ER-positive tumors from current HRT
users suggest a direct ER-mediated growth inhibitory effect of HRT on
established breast tumors. This may at least partly explain why breast
cancer in HRT users has a more favorable clinical course.
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