Effect of Hormone Replacement Therapy on Breast Cancer Risk: Estrogen Versus Estrogen Plus Progestin
Abstract
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(1/2) 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 (OR(5) = 1.10; 95% confidence interval [CI] = 1.02-1.18). Risk was substantially higher for CHRT use (OR(5) = 1.24; 95% CI = 1.07-1.45) than for ERT use (OR(5) = 1. 06; 95% CI = 0.97-1.15). Risk estimates were higher for SEPRT (OR(5) = 1.38; 95% CI = 1.13-1.68) than for CCRT (OR(5) = 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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Recent data suggest progestins exert a negative impact on breast cancer, with recent reports indicating an increased risk of the disease in women.
“recent data suggest that progestins exert a negative impact on breast cancer (2-5), with recent reports indicating an increased risk of the disease in women (6,7).”
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Garbe, J. C., Pepin, F., Pelissier, F. A., Sputova, K., Fridriksdottir, A. J., Guo, D. E., Villadsen, R., Park, M., PETERSEN, O. W., Borowsky, A. D., et al. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-0157 · Cited by 121 · see citing works
Ji, Q., Aoyama, C., Nien, Y.-D., Liu, P. I., Chen, P. K., Chang, L., Stanczyk, F. Z., & Stolz, A. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-1608 · Cited by 119 · see citing works
Chlebowski, R. T., Hendrix, S. L., Langer, R. D., Stefanick, M. L., Gass, M. L. S., Lane, D. S., Rodabough, R. J., Gilligan, M. A., Cyr, M. G., Thomson, C. A., et al. (2003) · Obstetrical & Gynecological Survey · doi:10.1097/01.ogx.0000093674.44946.d6 · Cited by 119 · see citing works
Racial differences in premenopausal endogenous hormones
Pinheiro, S. P., Holmes, M. D., Pollak, M. N., Barbieri, R. L., & Hankinson, S. E. (2005) · Cancer Epidemiology, Biomarkers & Prevention · doi:10.1158/1055-9965.epi-04-0944 · Cited by 119 · see citing works
- Authors
- Ross, R. K.
- Affiliations
- USC Norris Comprehensive Cancer Center (US)
- Corresponding author
- Ross, R. K.
- Venue
- Journal of the National Cancer Institute
- Publisher
- Oxford University Press (OUP)
- Published
- 2000-02-16
- Volume
- 92
- Issue
- 4
- Pages
- 328-332
- ISSN
- 0027-8874 (ISSN-L)
- 1460-2105
- OpenAlex
- W3022279537
- Cited by
- 877
- References
- 0
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 2 · 2023: 9 · 2022: 8 · 2021: 14 · 2020: 17 · 2019: 8 · 2018: 14 · 2017: 14 · 2016: 16 · 2015: 21 · 2014: 21 · 2013: 28 · 2012: 30
- FWCI
- 73.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JNCI Journal of the National Cancer Institute (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (n01pc067010-004)
- National Cancer Institute (CA 17054, P01CA017054, CA14089, P30CA014089, PC67010)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Oncology › Cancer Risks and Factors
- Keywords
- hormone replacement therapy, breast cancer risk, estrogen plus progestin, postmenopausal women, hormone-dependent breast cancer, breast cancer risk factors, duration of HRT use, Los Angeles
- MeSH terms
- Aged, Breast Neoplasms, California, Estrogens, Female, Humans, Middle Aged, Progestins, Risk, Risk Factors, Time Factors, Estrogen Replacement Therapy, Odds Ratio, Case-Control Studies
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