Cited by 888Menopause: Health Impacts and TreatmentsEstrogen and related hormone effectsCancer Risks and Factors

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Effect of Hormone Replacement Therapy on Breast Cancer Risk: Estrogen Versus Estrogen Plus Progestin

Ross, R. K.·2000·Journal of the National Cancer Institute

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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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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
DOI: 10.1093/jnci/92.4.328
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 › Endocrinology › 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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Effect of Hormone Replacement Therapy on Breast Cancer Risk: Estrogen Versus Estrogen Plus Progestin

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