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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 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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“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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Huang, P.-H., Huang, C., Chen, M., Lee, Y.-T., Yue, C.-H., Wang, H., & Lin, H. (2013) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2013/376123 · Cited by 131
Coronary heart disease: an older woman's major health risk
WENGER, N. K. (1997) · BMJ · doi:10.1136/bmj.315.7115.1085 · Cited by 129
Crisafulli, A., Marini, H. R., Bitto, A., Altavilla, D., Squadrito, G., Romeo, A., Adamo, E. B., Marini, R., D’Anna, R., Corrado, F., et al. (2004) · Menopause The Journal of The North American Menopause Society · doi:10.1097/01.gme.0000109314.11228.e5 · Cited by 128
Kerlikowske, K. M., Miglioretti, D. L., Ballard-Barbash, R. R., Weaver, D. L., Buist, D. S. M., Barlow, W. E., Cutter, G., Geller, B. M., Yankaskas, B. C., Taplin, S. H., et al. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.05.151 · Cited by 129
Influence of education level on breast cancer risk and survival in Sweden between 1990 and 2004
Hussain, S. K., Altieri, A., Sundquist, J., & Hemminki, K. (2007) · International Journal of Cancer · doi:10.1002/ijc.23007 · Cited by 127
Long-term cancer risk in women given diethylstilbestrol (DES) during pregnancy
Titus-Ernstoff, L. T., Hatch, E. E., Hoover, R. N., Palmer, J. R., Greenberg, E. R., Ricker, W., Kaufman, R. H., Noller, K. L., Herbst, A. L., Colton, T., et al. (2001) · British Journal of Cancer · doi:10.1054/bjoc.2000.1521 · Cited by 127
“A possible causal role for DES receives some support from evidence for an association between HRT and breast cancer risk (Colditz et al, 1995; CGHFBC, 1997; Schairer et al, 2000), generally with recent, long-term use; in contrast, DES exposure was brief, even for women with multiple exposed…”
Managing side effects in adjuvant endocrine therapy for breast cancer
Condorelli, R., & Vaz-Luís, I. (2018) · Expert Review of Anticancer Therapy · doi:10.1080/14737140.2018.1520096 · Cited by 132
Grese, T. A., Pennington, L. D., Sluka, J. P., Adrian, M. D., Cole, H. W., Fuson, T. R., Magee, D. E., Phillips, D. L., Rowley, E. R., Shetler, P. K., et al. (1998) · Journal of Medicinal Chemistry · doi:10.1021/jm970688z · Cited by 126
Phytoestrogens: endocrine disrupters or replacement for hormone replacement therapy?
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“[2] Colditz GA, Hankinson SE, Hunter DJ, et al.”
BackgroundA Review of the Effectiveness of Cimicifuga racemosa (Black Cohosh) for the Symptoms of Menopause
Lieberman, S. (1998) · Journal of Women s Health · doi:10.1089/jwh.1998.7.525 · Cited by 123
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Mechanisms of Cyclin-Dependent Kinase Inactivation by Progestins
Musgrove, E. A., Swarbrick, A., Lee, C. S. L., Cornish, A. L., & Sutherland, R. L. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.4.1812 · Cited by 123
“In contrast, while the effect of hormonal therapies on breast cancer risk has been controversial, there appears to be a slight increase in risk in recent or current users (7, 8), and in postmenopausal women the risk of breast cancer associated with estrogen use does not appear to be reduced by the addition of progesti…”
BackgroundOne-carbon metabolism-related gene polymorphisms and risk of breast cancer
Suzuki, T., Matsuo, K., Hirose, K., Hiraki, A., Kawase, T., Watanabe, M., Yamashita, T., Iwata, H., & Tajima, K. (2008) · Carcinogenesis · doi:10.1093/carcin/bgm295 · Cited by 119
Santoro, N. F. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.6.5765-1 · Cited by 122
Breast cancer risk factors in relation to breast density (United States)
Titus-Ernstoff, L. T., Tosteson, A. N. A., Kasales, C. J., Weiss, J. E., Goodrich, M., Hatch, E. E., & Carney, P. A. (2006) · Cancer Causes & Control · doi:10.1007/s10552-006-0071-1 · Cited by 122
“A prospective study of breast cancer risk also noted stronger HT effects in older women [37], although this is not always seen [36].”
Kim, J., & Münster, P. N. (2024) · Annals of Oncology · doi:10.1016/j.annonc.2024.10.824 · Cited by 134
Recent trends in breast cancer mortality among white and black US women.
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Cancer Risk Associated with Subfertility and Ovulation Induction: A Review
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“However, there are problems associated with long-term HRT, such as the possible increased risk of breast cancer and symptoms of breast tenderness and mood changes, etc. (Colditz et al. 1995; Selby and Peacock 1986).”
BackgroundRacial 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
“Some studies, although not all (52-55), suggest that the use of estrogen and progestins in hormone replacement therapy may increase breast cancer risk beyond that following use of estrogen alone (56-58).”
BackgroundBreast Cancer Screening in Older Women
Caplan, L. S., & Haynes, S. G. (2000) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2000.tb04763.x · Cited by 119
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Metadata
- 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 › Endocrinology › 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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