© 2000 by Oxford University Press
Journal of the National Cancer Institute, Vol. 92, No. 4, 328-332,
February 16, 2000
© 2000 Oxford University Press
REPORTS |
Effect of Hormone Replacement Therapy on Breast Cancer Risk: Estrogen Versus Estrogen Plus Progestin
Affiliation of authors: University of Southern California/Norris Comprehensive Cancer Center, Los Angeles.
Correspondence to: Ronald K. Ross, M.D., University of Southern California/Norris Comprehensive Cancer Center, 1441 Eastlake Ave., Rm. 8302B, Los Angeles, CA 90089-9181 (e-mail: ross_r{at}ccnt.hsc.usc.edu).
BACKGROUND: Hormone replacement therapy (HRT) given as unopposed estrogen
replacement
therapy (ERT) gained widespread popularity in the United States in the 1960s and 1970s. Recent
prescribing practices have favored combination HRT (CHRT), i.e., adding a progestin to estrogen
for
the entire monthly cycle (continuous combined replacement therapy [CCRT]) or a
part of
the cycle (sequential estrogen plus progestin therapy [SEPRT]). Few data exist on the
association between CHRT and breast cancer risk. We determined the effects of CHRT on a
woman's risk of developing breast cancer in a population-based, case-control study.
METHODS: Case subjects included those with incident breast cancers diagnosed over 4
years in Los Angeles County, CA, in the late 1980s and 1990s. Control subjects were
neighborhood
residents who were individually matched to case subjects on age and race. Case subjects and
control
subjects were interviewed in person to collect information on known breast cancer risk factors as
well
as on HRT use. Information on 1897 postmenopausal case subjects and on 1637 postmenopausal
control subjects aged 55-72 years who had not undergone a simple hysterectomy was analyzed.
Breast
cancer risks associated with the various types of HRT were estimated as odds ratios (ORs) after
adjusting simultaneously for the different forms of HRT and for known risk factors of breast
cancer. All P values are two-sided. RESULTS: HRT was associated with a 10%
higher
breast cancer risk for each 5 years of use (OR5 = 1.10; 95% confidence
interval [CI] = 1.02-1.18). Risk was substantially higher for CHRT use (OR5 = 1.24; 95% CI = 1.07-1.45) than for ERT use (OR5
= 1.06; 95% CI = 0.97-1.15). Risk estimates were higher for SEPRT (OR5 = 1.38; 95% CI = 1.13-1.68) than for CCRT (OR5
=
1.09; 95% CI = 0.88-1.35), but this difference was not statistically significant. Conclusions: This study provides strong evidence that the addition of a progestin to HRT
enhances
markedly the risk of breast cancer relative to estrogen use alone. These findings have important
implications for the risk-benefit equation for HRT in women using CHRT.
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