The use of estrogens and progestins and the risk of breast cancer in postmenopausal women.
Open accessAbstract
BACKGROUND: The effect of adding progestins to estrogen therapy on the risk of breast cancer in postmenopausal women is controversial. METHODS: To quantify the relation between the use of hormones and the risk of breast cancer in postmenopausal women, we extended our follow-up of the participants in the Nurses' Health Study to 1992. The women were asked to complete questionnaires every two years to update information on their menopausal status, use of estrogen and progestin preparations, and any diagnosis of breast cancer. During 725,550 person-years of follow-up, we documented 1935 cases of newly diagnosed invasive breast cancer. RESULTS: The risk of breast cancer was significantly increased among women who were currently using estrogen alone (relative risk, 1.32; 95 percent confidence interval, 1.14 to 1.54) or estrogen plus progestin (relative risk, 1.41; 95 percent confidence interval, 1.15 to 1.74), as compared with postmenopausal women who had never used hormones. Women currently taking hormones who had used such therapy for 5 to 9 years had an adjusted relative risk of breast cancer of 1.46 (95 percent confidence interval, 1.22 to 1.74), as did those currently using hormones who had done so for a total of 10 or more years (relative risk, 1.46; 95 percent confidence interval, 1.20 to 1.76). The increased risk of breast cancer associated with five or more years of postmenopausal hormone therapy was greater among older women (relative risk for women 60 to 64 years old, 1.71; 95 percent confidence interval, 1.34 to 2.18). The relative risk of death due to breast cancer was 1.45 (95 percent confidence interval, 1.01 to 2.09) among women who had taken estrogen for five or more years. CONCLUSIONS: The addition of progestins to estrogen therapy does not reduce the risk of breast cancer among postmenopausal women. The substantial increase in the risk of breast cancer among older women who take hormones suggests that the trade-offs between risks and benefits should be carefully assessed.
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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).”
Use of ERT requires addition of progestins to counteract endometrial proliferation induced by estrogens, whereas both estrogens and progestins could increase risk of breast cancer.
“The use of ERT requires the addition of progestins to counteract the endometrial proliferation induced by estrogens, whereas both estrogens and progestins could increase the risk of breast cancer (5,318).”
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“Observational studies have shown that women who use HRT have a substantially decreased risk for coronary artery disease (6–8), osteoporosis and fractures (8–10), and death (12), but they may also have an increased risk for breast cancer (13).”
BackgroundPostmarketing Surveillance and Adverse Drug Reactions
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BackgroundBreast cancer: hormones and other risk factors
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“Reports from both the Collaborative Group on Hormonal Factors in Breast Cancer and the US Nurses Health Study support these risk estimates [33,34].”
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Induction of uterine adenocarcinoma in CD-1 mice by catechol estrogens.
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“modest, but nevertheless concerning, increased incidence of breast cancer in women taking estrogens is a major limitation of this prophylactic therapy (14).”
BackgroundHuang, W., Newman, B. M., Millikan, R. C., Schell, M. J., Hulka, B. S., & Moorman, P. G. (2000) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a010265 · Cited by 278 · see citing works
“Estrogen and progesterone help regulate growth and differentiation of normal breast tissue, and they are considered important in the development and progression of breast cancer (1-4).”
BackgroundWuttke, W., Seidlová‐Wuttke, D., & Gorkow, C. (2003) · Maturitas · doi:10.1016/s0378-5122(02)00350-x · Cited by 278 · see citing works
Labrie, F., Diamond, P., Cusan, L., Gomez, J.-L., Bélanger, A., & Candas, B. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.10.4306 · Cited by 292 · see citing works
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“Although the benefits of estrogen therapy outweigh the risks in most women, concern about risk for breast cancer is sufficiently great that many women avoid estrogen therapy (14, 15).”
BackgroundThird consensus on medical treatment of metastatic breast cancer
Beslija, S., Bonneterre, J. M., Burstein, H. J., Cocquyt, V. F. J., Gnant, M., Heinemann, V., Jassem, J., Köstler, W. J., Krainer, M., Ménard, S., et al. (2009) · Annals of Oncology · doi:10.1093/annonc/mdp261 · Cited by 263 · see citing works
“Based upon scientific evidence causally linking the use of HRT to the development of breast cancer [164, 165], the use of HRT in MBC is strongly discouraged, as HRT may stimulate growth of hormone receptor-positive cancers.”
BackgroundIndolizine: a biologically active moiety
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“…changes like heart disease and osteoporosis; Jorgensen et al. 2000a, claiming to be the first to report the synthesis of a non-steroidal full estrogen agonist, synthesized various pyrroloindolizine derivatives (Jorgensen et al., 2000b; Lobo, 1997; Colditz et al., 1995; Stanford et al., 1995).”
BackgroundChapter 5: Tissue-Specific Synthesis and Oxidative Metabolism of Estrogens
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Risks of breast and endometrial cancer after estrogen and estrogen–progestin replacement
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BackgroundResultGuide to Clinical Preventive Services: Report of the US Preventive Services Task Force
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Unopposed Estrogen Therapy and the Risk of Invasive Breast Cancer
Chen, W. Y., Manson, J. E., Hankinson, S. E., ROSNER, B. A., Holmes, M. D., Willett, W. C., & Colditz, G. A. (2006) · Archives of Internal Medicine · doi:10.1001/archinte.166.9.1027 · Cited by 248 · see citing works
“Our research group has previously published on the relation between PMH and breast cancer within the NHS, but most of these analyses grouped together ET and combination regimens of estrogen and progesterone.(14,15) In 2000, our group published a log incidence model for cumulative lifetime breast cancer risk and estima…”
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“[3] Colditz GA, Hankinson SE, Hunter DJ, et al.”
BackgroundTreatment of Established Postmenopausal Osteoporosis with Raloxifene: A Randomized Trial
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“Most importantly, there are recent data that support strongly the contention that long-term estrogen therapy is associated with an increased risk for breast cancer.((25)) Even though this is still a subject of debate,((26)) the issue has had wide coverage in the mass media, and a general TABLE 5.”
BackgroundSquadrito, F., Altavilla, D., Morabito, N., Crisafulli, A., D’Anna, R., Corrado, F., Ruggeri, P., Campo, G. M., Calapai, G., Caputi, A. P., et al. (2002) · Atherosclerosis · doi:10.1016/s0021-9150(02)00013-8 · Cited by 230 · see citing works
Patient-specific decisions about hormone replacement therapy in postmenopausal women
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Efficacy of estrogen supplementation in the treatment of urinary incontinence
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Low-Dose Esterified Estrogen Therapy
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The physiological actions of isoflavone phytoestrogens
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Effects of Alcohol Ingestion on Estrogens in Postmenopausal Women
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Failure of Estrogen Plus Progestin Therapy for Prevention
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Chlebowski, R. T., Manson, J. E., Anderson, G. L., Cauley, J. A., Aragaki, A. K., Stefanick, M. L., Lane, D. S., Johnson, K., Wactawski‐Wende, J., Chen, C., et al. (2013) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djt043 · Cited by 205 · see citing works
“These findings were similar to observational study results regarding incidence (4) but differ from most reports regarding tumor characteristics and clinical outcome, in which a decrease (5–8) in deaths after breast cancer is commonly, but not universally (9), seen.”
BackgroundResult
- Authors
- Colditz, G. A., Hankinson, S. E., Hunter, D. J., Willett, W. C., Manson, J. E., Stampfer, M. J., Hennekens, C., Rosner, B., & Speizer, F. E.
- Affiliations
- Brigham and Women's Hospital (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 1995-06-15
- Volume
- 332
- Issue
- 24
- Pages
- 1589-1593
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2607238143
- Cited by
- 1,487
- References
- 32
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 6 · 2023: 8 · 2022: 8 · 2021: 13 · 2020: 13 · 2019: 11 · 2018: 17 · 2017: 16 · 2016: 16 · 2015: 18 · 2014: 21 · 2013: 18 · 2012: 26
- FWCI
- 111.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA 40956)
- 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
- breast cancer risk, hormone replacement therapy, estrogen therapy, progestins, estrogen plus progestin, duration of hormone use, age-related risk, breast cancer mortality, Nurses' Health Study
- MeSH terms
- Aged, Breast Neoplasms, Estrogens, Female, Follow-Up Studies, Humans, Middle Aged, Progestins, Prospective Studies, Risk, Risk Factors, Cohort Studies, Estrogen Replacement Therapy, Confidence Intervals, Case-Control Studies, Postmenopause
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