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J Clin Oncol. 2002 Feb 1;20(3):699-706.

Does menopausal hormone replacement therapy interact with known factors to increase risk of breast cancer?

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  • 1Department of Preventive Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA 90089, USA.



We and other investigators have previously shown that postmenopausal combined estrogen and progestin replacement therapy (EPRT) increases the risk of breast cancer and that the risk associated with EPRT is substantially higher than for estrogen replacement therapy (ERT) alone. The present study was conducted to determine whether any particular subgroup of women are at particularly high risk of breast cancer if they use EPRT and whether tumor characteristics in women who develop cancer while on ERT or EPRT are different from those in women not using ERT or EPRT.


We conducted a population-based case-control study in Los Angeles, CA, with patients diagnosed with breast cancer in the late 1980s and early 1990s. Control subjects were matched to patients on age, ethnicity, and neighborhood of residence. We present data on 1,897 postmenopausal patients and 1,637 controls aged 55 to 72 years who had not undergone a simple hysterectomy.


Relative risk of breast cancer associated with EPRT use did not vary with body mass index (body mass index at or below v above median [24.6 kg/m(2)]; P =.98), alcohol intake (> or + one v < one drink per week; P =.16), parity (nulliparous v parous; P =.45), history of benign breast disease (yes v no; P =.99), or family history of breast cancer (first degree v none; P =.57). All of these results were compatible with our previously reported estimate of an increased risk of breast cancer of 5% per year of use of EPRT. Hormone users, principally EPRT users, were more likely to have hormone receptor--positive, especially progesterone-positive, tumors.


We found no evidence that the risk of breast cancer associated with EPRT is limited to subgroups of women with specific cofactors. Tumors in EPRT users are more often hormone receptor--positive, indicating that they may have a better prognosis than breast cancer overall.

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