Cited by 1,487Menopause: Health Impacts and TreatmentsEstrogen and related hormone effectsCancer Risks and Factors

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The use of estrogens and progestins and the risk of breast cancer in postmenopausal women.

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Colditz, Graham A., Hankinson, Susan E., Hunter, David J., Willett, Walter C., Manson, JoAnn E., Stampfer, Meir J., Hennekens, Charles, Rosner, Bernard, Speizer, Frank E.·1995·New England Journal of Medicine

DOI 10.1056/nejm199506153322401

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Abstract

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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Regression Models and Life-Tables
Cox, D. R. (1972) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1972.tb00899.x · Cited by 39,793
Variations in mortality by weight among 750,000 men and women
Lew, E. A., & Garfinkel, L. (1979) · Journal of Chronic Diseases · doi:10.1016/0021-9681(79)90119-x · Cited by 1,169
Estrogens, Progestogens, Normal Breast Cell Proliferation, and Breast Cancer Risk
Pike, M. C., SPICER, D. V., Dahmoush, L., & Press, M. F. (1993) · Epidemiologic Reviews · doi:10.1093/oxfordjournals.epirev.a036102 · Cited by 1,009
TEST OF THE NATIONAL DEATH INDEX
Stampfer, M. J., Willett, W. C., Speizer, F. E., DYSERT, D. C., LIPNICK, R. J., ROSNER, B. A., & Hennekens, C. H. (1984) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a113804 · Cited by 791
The role of oestrogens and progestagens in the epidemiology and prevention of breast cancer
Key, T. J., & Pike, M. C. (1988) · European Journal of Cancer and Clinical Oncology · doi:10.1016/0277-5379(88)90173-3 · Cited by 658
The Risk of Breast Cancer after Estrogen and Estrogen–Progestin Replacement
Bergkvist, L., Adami, H., Persson, I. R., Hoover, R. N., & Schairer, C. (1989) · New England Journal of Medicine · doi:10.1056/nejm198908033210505 · Cited by 612
The Effect of Postmenopausal Estrogen Therapy on Bone Density in Elderly Women
Felson, D. T., Zhang, Y., Hannan, M. T., Kiel, D. P., Wilson, P. W. F., & Anderson, J. J. (1993) · New England Journal of Medicine · doi:10.1056/nejm199310143291601 · Cited by 580
THE EPIDEMIOLOGY OF SERUM SEX HORMONES IN POSTMENOPAUSAL WOMEN
Cauley, J. A., Gutai, J. P., Kuller, L. H., LEDONNE, D., & POWELL, J. G. (1989) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a115234 · Cited by 485
Biologic Effects of Transdermal Estradiol
Chetkowski, R. J., Meldrum, D. R., Steingold, K. A., Randle, D., Lu, J. K., Eggena, P., Hershman, J. M., Alkjaersig, N. K., Fletcher, A. P., & Judd, H. L. (1986) · New England Journal of Medicine · doi:10.1056/nejm198606193142505 · Cited by 482
Biologic effects of transdermal estradiol
Chetkowski, R. J., Meldrum, D., & Ka, S. (1987) · International Journal of Gynecology & Obstetrics · doi:10.1016/0020-7292(87)90325-0 · Cited by 467

Show all 32 references

Research works printed but not linked: 4

Feinleib M, 1968, J Natl Cancer Inst, 41, 315
Committee on the relationship Between Oral Contraceptives and Breast Cancer, Institute of Medicine. Oral contraceptives & breast cancer. Washington, D.C.: National Academy Press, 1991.
Gambrell RD, 1983, Obstet Gynecol, 62, 435
Rose DP, 1977, Obstet Gynecol, 49, 80

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Li, C. I., & Daling, J. R. (2007) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-07-0546 · Cited by 106
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Method
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Nuñez, S. B., Medin, J. A., Braissant, O., Kemp, L., Wahli, W., Ozato, K., & Segars, J. H. (1997) · Molecular and Cellular Endocrinology · doi:10.1016/s0303-7207(96)03980-9 · Cited by 101
MENOPAUSE AND HORMONE REPLACEMENT THERAPY
Johnson, S. R. (1998) · Medical Clinics of North America · doi:10.1016/s0025-7125(05)70608-8 · Cited by 104
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Shimizu, I., & Ito, S. (2007) · Hepatology Research · doi:10.1111/j.1872-034x.2007.00032.x · Cited by 103
Kistner's Gynecology and Women's Health
Ryan, K. J. (1999) · Cited by 104
Body mass index and post-menopausal breast cancer: an age-specific analysis
Vecchia, C. L., Negri, E., Franceschi, S., Talamini, R., Bruzzi, P., Palli, D., & Decarli, A. (1997) · British Journal of Cancer · doi:10.1038/bjc.1997.73 · Cited by 102
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Zeligs, M. A. (1998) · Journal of Medicinal Food · doi:10.1089/jmf.1998.1.67 · Cited by 100
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Background
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Cause-Specific Mortality in Women Receiving Hormone Replacement Therapy
Schairer, C., Adami, H., Hoover, R. N., & Persson, I. R. (1997) · Epidemiology · doi:10.1097/00001648-199701000-00010 · Cited by 100
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Background
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Background
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Background
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“Elevated breast cancer risks among estrogen plus progestin users first emerged in the mid-1990s to late 1990s (17, 29).”
Background
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“There are, however, shortfalls in the way information has been collected and analysed in most published epidemiological studies (Colditz et al, 1995; Magnusson et al, 1999; Li et al, 2000; Schairer et al, 2000; Daling et al, 2002; Newcomb et al, 2002; Beral and Million Women Study Collaborators,…”
BackgroundMethodResultInfluential
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Wu, A. H. (2000) · Cancer · doi:10.1002/(sici)1097-0142(20000301)88:5+ · Cited by 18
Risk factors for carcinoma in situ of the breast.
Trentham‐Dietz, A., Newcomb, P. A., Storer, B. E., & Remington, P. L. (2000) · PubMed · Cited by 93
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Biglia, N., Mariani, L. L., Sgrò, L. G., Mininanni, P., Moggio, G., & Sismondi, P. (2007) · Endocrine Related Cancer · doi:10.1677/erc-06-0060 · Cited by 93
“…have shown a more pronounced negative effect on breast cancer risk of oestrogen plus progestin associations as compared with oestrogen alone (ERT; Colditz et al. 1995, Persson et al. 1996, Colditz & Rosner 1998, Magnusson et al. 2000, Ross et al. 2000, Schairer et al. 2000, Rossouw et al. 2002,…”
Background
Hormone-associated cancer: mechanistic similarities between human breast cancer and estrogen-induced kidney carcinogenesis in hamsters.
Liehr, J. G. (1997) · Environmental Health Perspectives · doi:10.1289/ehp.97105s3565 · Cited by 91
“Progestin added to the estrogen medications does not inhibit mammary carcinogenesis (8) because the former hormone appears to be the primary mitogen of mammary ductal epithelial cells (9), whereas estrogen appears to function in”
Background
Individualizing osteoporosis therapy
Silverman, S. L., & Christiansen, C. (2012) · Osteoporosis International · doi:10.1007/s00198-011-1775-y · Cited by 90
Different menopausal hormone regimens and risk of breast cancer
Brusselaers, N., Tamimi, R. M., Könings, P., ROSNER, B. A., Adami, H., & Lagergren, J. (2018) · Annals of Oncology · doi:10.1093/annonc/mdy212 · Cited by 90
Altered retinoblastoma protein expression in nonsmall cell lung cancer
Dosaka‐Akita, H., Hu, S., Fujino, M., Harada, M., Kinoshita, I., Xu, H., Kuzumaki, N., Kawakami, Y., & Benedict, W. F. (1997) · Cancer · doi:10.1002/(sici)1097-0142(19970401)79:7 · Cited by 97
Estrogen Replacement Therapy in Women with Prior Diagnosis and Treatment for Breast Cancer
Vassilopoulou‐Sellin, R., Theriault, R. L., & Klein, M. J. (1997) · Gynecologic Oncology · doi:10.1006/gyno.1997.4621 · Cited by 89
Effects of the phytoestrogen genistein on cardiovascular risk factors in postmenopausal women
Crisafulli, A., Altavilla, D., Marini, H. R., Bitto, A., Cucinotta, D., Frisina, N., Corrado, F., D’Anna, R., Squadrito, G., Adamo, E. B., et al. (2005) · Menopause The Journal of The North American Menopause Society · doi:10.1097/00042192-200512020-00013 · Cited by 91
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Nachtigall, L. E., Casson, P. R., Lucas, J. D., Schofield, V., Melson, C., & Simon, J. A. (2010) · Gynecological Endocrinology · doi:10.3109/09513590.2010.487597 · Cited by 88
Breast cancer prevention: a review of current evidence
Vogel, V. G. (2000) · CA A Cancer Journal for Clinicians · doi:10.3322/canjclin.50.3.156 · Cited by 87
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Mosca, L. J. (2000) · Archives of Internal Medicine · doi:10.1001/archinte.160.15.2263 · Cited by 87
First-time proof of endometrial safety of the special black cohosh extract (Actaea or Cimicifuga racemosa extract) CR BNO 1055
Rauš, K., Brucker, C. V. M., Gorkow, C., & Wuttke, W. (2006) · Menopause The Journal of The North American Menopause Society · doi:10.1097/01.gme.0000196813.34247.e2 · Cited by 84
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Simon, K. C., Chen, H., Gao, X., Schwarzschild, M. A., & Ascherio, A. (2009) · Movement Disorders · doi:10.1002/mds.22619 · Cited by 87
“Further, the validity of history of estrogen use and reproductive factors in our study is supported by the previous finding that these factors were strong predictors of ovarian and breast cancer in this cohort.(29,30) Although the confirmation of PD diagnoses relied on reports from the treating neurologists or review…”
Result
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Meunier, P. J., Confavreux, E., Tupinon, I., Hardouin, C., Delmas, P. D., & Balena, R. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.9.4073 · Cited by 85
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Background
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Burdette, J. E., Liu, J., Lantvit, D., Lim, E., Booth, N. L., Bhat, K., Hedayat, S., van Breemen, R. B., Constantinou, A. I., Pezzuto, J. M., et al. (2002) · Journal of Nutrition · doi:10.1093/jn/132.1.27 · Cited by 84
Case-control study of increased mammographic breast density response to hormone replacement therapy.
Vachon, C. M., Sellers, T. A., Vierkant, R. A., Wu, F.-F., & Brandt, K. R. (2002) · PubMed · Cited by 83
OSTEOPOROSIS
Kenny, A. M., & Prestwood, K. M. (2000) · Rheumatic Disease Clinics of North America · doi:10.1016/s0889-857x(05)70157-5 · Cited by 83
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Menopausal hormone therapy and risk of breast cancer: a meta-analysis of epidemiological studies and randomized controlled trials
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BackgroundResultInfluential
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Gomez, S. L., Tan, S. K., Keegan, T. H. M., & Clarke, C. A. (2007) · BMC Cancer · doi:10.1186/1471-2407-7-201 · Cited by 81
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Zhang, F., Chen, Y., Pisha, E., Shen, L., Xiong, Y., van Breemen, R. B., & Bolton, J. L. (1999) · Chemical Research in Toxicology · doi:10.1021/tx980217v · Cited by 81
Geriatric medicine: a brief history
Evans, J. G. (1997) · BMJ · doi:10.1136/bmj.315.7115.1075 · Cited by 83
Osteoporotic fractures: background and prevention strategies
Wark, J. D. (1996) · Maturitas · doi:10.1016/0378-5122(95)00974-4 · Cited by 79
Equine Estrogen Metabolite 4-Hydroxyequilenin Induces DNA Damage in the Rat Mammary Tissues: Formation of Single-Strand Breaks, Apurinic Sites, Stable Adducts, and Oxidized Bases
Zhang, F., Swanson, S. M., van Breemen, R. B., Liu, X., Yang, Y., Gu, C., & Bolton, J. L. (2001) · Chemical Research in Toxicology · doi:10.1021/tx010158c · Cited by 80
Hormone replacement therapy as a risk factor for epithelial ovarian cancer: Results of a case-control study
Hempling, R. E., WONG, C., STEVENPIVER, M., NATARAJAN, N., & Mettlin, C. J. (1997) · Obstetrics and Gynecology · doi:10.1016/s0029-7844(97)00118-x · Cited by 80
Menopausal Hormone Therapy and Breast Cancer Risk in the NIH-AARP Diet and Health Study Cohort
Brinton, L. A., Richesson, D. A., Leitzmann, M. F., Gierach, G. L., Schatzkin, A. G., Mouw, T., Hollenbeck, A. R., & Lacey, J. V. (2008) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-08-0435 · Cited by 79
“Further, questions exist about the role of unopposed estrogen therapy (ET), which has been linked to elevated breast cancer risks in numerous observational studies (7) but not in WHI (2).”
Background
Postmenopausal hormone therapy and breast cancer: a systematic review and meta-analysis
Shah, N. R., Borenstein, J. E., & Dubois, R. W. (2005) · Menopause The Journal of The North American Menopause Society · doi:10.1097/01.gme.0000184221.63459.e1 · Cited by 78
Ultrafiltration tandem mass spectrometry of estrogens for characterization of structure and affinity for human estrogen receptors
Sun, Y., Gu, C., Liu, X., Liang, W., Yao, P., Bolton, J. L., & van Breemen, R. B. (2004) · Journal of the American Society for Mass Spectrometry · doi:10.1016/j.jasms.2004.11.002 · Cited by 79
“Hormone replacement therapy (HRT) may be used to reduce these symptoms and perhaps even reduce the postmenopausal risk of certain age-related disorders such as osteoporosis [8, 9].”
Background
Perspectives on the Women's Health Initiative trial of hormone replacement therapy
Grimes, D. A. (2002) · Obstetrics and Gynecology · doi:10.1016/s0029-7844(02)02503-6 · Cited by 77
“The potential association between ERT or HRT and breast cancer has received intensive scrutiny over the years.(50,51) The findings of the Women’s Health Initiative are consistent with a small increase in risk (26%) (Figure 1).”
Background
Effects of ospemifene and raloxifene on biochemical markers of bone turnover in postmenopausal women
Komi, J., Lankinen, K. S., DeGregorio, M. W., Heikkinen, J. E., Saarikoski, S., Tuppurainen, M. T., Halonen, K., Lammintausta, R. A. S., Väänänen, K., Ylikorkala, O., et al. (2006) · Journal of Bone and Mineral Metabolism · doi:10.1007/s00774-006-0689-9 · Cited by 77
Estrogen, Estrogen Plus Progestin Therapy, and Risk of Breast Cancer
Colditz, G. A. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.909s.11.2 · Cited by 77
Increased brain serotonin function in men with chronic fatigue syndrome: Fig 1
Sharpe, M., Hawton, K. E., Clements, A., & Cowen, P. J. (1997) · BMJ · doi:10.1136/bmj.315.7101.164 · Cited by 77
High-risk mammographic parenchymal patterns, hormone replacement therapy and other risk factors: a case-control study
Sala, E., Warren, R. M. L., McCann, J., Duffy, S. W., Luben, R., & Day, N. M. (2000) · International Journal of Epidemiology · doi:10.1093/ije/29.4.629 · Cited by 77
Raloxifene Causing Malabsorption of Levothyroxine
Siraj, E. S., Gupta, M. K., & Reddy, S. S. K. (2003) · Archives of Internal Medicine · doi:10.1001/archinte.163.11.1367 · Cited by 76
Digoxin Use and the Risk of Breast Cancer in Women
Biggar, R. J., Wohlfahrt, J., Oudin, A., Hjuler, T., & Melbye, M. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.32.8146 · Cited by 76
Estrogen replacement in menopausal women: Recent and current prospective studies, the WHI and the KEEPS
Harman, S. M. (2006) · Gender Medicine · doi:10.1016/s1550-8579(06)80214-7 · Cited by 76
Reprint of Breast cancer: hormones and other risk factors
Hulka, B. S., & Moorman, P. G. (2008) · Maturitas · doi:10.1016/j.maturitas.2008.11.016 · Cited by 75
Hormone Replacement Therapy in Postmenopausal Women: Breast Tissue Perfusion Determined with MR Imaging—Initial Observations
Delille, J.-P., Slanetz, P. J., Yeh, E. D., Kopans, D. B., Halpern, E. F., & Garrido, L. (2005) · Radiology · doi:10.1148/radiol.2351040012 · Cited by 75
Efficacy and safety of a special extract of Rheum rhaponticum (ERr 731) in perimenopausal women with climacteric complaints
Heger, M., Ventskovskiy, B. M., Borzenko, I., Kneis, K. C., Rettenberger, R., Kaszkin-Bettag, M., & Heger, P. W. (2006) · Menopause The Journal of The North American Menopause Society · doi:10.1097/01.gme.0000240632.08182.e4 · Cited by 74
Effects of phytoestrogenic isoflavones from red clover (Trifolium pratense L.) on experimental osteoporosis
Occhiuto, F., Pasquale, R. D., Guglielmo, G., Palumbo, D. R., Zangla, G., Samperi, S., Renzo, A., & Circosta, C. (2006) · Phytotherapy Research · doi:10.1002/ptr.2037 · Cited by 75
“Since the side-effects of estrogen replacement therapy include a slight but significant increase in the risk of developing breast and endometrial cancer (Colditz et al., 1995), women are increasingly using herbal remedies as an alternative therapy (Murkies et al., 1998).”
The Medicalization of Menopause: Critique and Consequences
Meyer, V. (2001) · International Journal of Health Services · doi:10.2190/m77d-yv2y-d5nu-fxnw · Cited by 78
Hormone replacement therapy and tumour grade in breast cancer: prospective study in screening unit: Table 1
Harding, C., Knox, W. F., Faragher, E. B., Baildam, A. D., & Bundred, N. J. (1996) · BMJ · doi:10.1136/bmj.312.7047.1646 · Cited by 75
The effect of tibolone and continuous combined conjugated equine oestrogens plus medroxyprogesterone acetate on progression of carotid intima–media thickness: the Osteoporosis Prevention and Arterial effects of tiboLone (OPAL) study
Bots, M. L., Evans, G. W., Riley, W. A., McBride, K., Paskett, E. D., Helmond, F. A., & Grobbee, D. E. (2006) · European Heart Journal · doi:10.1093/eurheartj/ehi695 · Cited by 74
Effect of Body Mass on the Association between Estrogen Replacement Therapy and Mortality among Elderly US Women
Rodríguez, C., Calle, E. E., Patel, A. V., Tatham, L. M., Jacobs, E. J., & Thun, M. J. (2001) · American Journal of Epidemiology · doi:10.1093/aje/153.2.145 · Cited by 74
The critical role of bisphosphonates to target bone cancer metastasis: an overview
Singh, T., Kaur, V., Kumar, M., Kaur, P., Murthy, R. S. R., & Rawal, R. K. (2014) · Journal of drug targeting · doi:10.3109/1061186x.2014.950668 · Cited by 73
A Phytoestrogen Diarylheptanoid Mediates Estrogen Receptor/Akt/Glycogen Synthase Kinase 3β Protein-dependent Activation of the Wnt/β-Catenin Signaling Pathway
Bhukhai, K., Suksen, K., Bhummaphan, N., Janjorn, K., Thongon, N., Tantikanlayaporn, D., Piyachaturawat, P., Suksamrarn, A., & Chairoungdua, A. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.344747 · Cited by 74
“However, long-term supplementationwith estrogen increased the risk of breast cancer (11) and endometrial cancer (12).”
Background
Mammographic density in women on postmenopausal hormone replacement therapy
Leung, W., Goldberg, F., Zee, B. C.-Y., & Sterns, E. E. (1997) · Surgery · doi:10.1016/s0039-6060(97)90072-6 · Cited by 73
A Prospective Study of Infertility Due to Ovulatory Disorders, Ovulation Induction, and Incidence of Breast Cancer
Terry, K. L. (2006) · Archives of Internal Medicine · doi:10.1001/archinte.166.22.2484 · Cited by 72
“Subsequent epidemiologic evidence indicated that exogenous estrogen plus progestin increases breast cancer risk beyond that of estrogen alone.(7,8) However, these studies were restricted to postmenopausal women; whether these combinations have a similar influence on premenopausal breast cancer risk is not known.”
Background
Demographics, family histories, and psychological characteristics of prostate carcinoma screening participants
Taylor, K. L., DiPlacido, J., Redd, W. H., Faccenda, K., Greer, L., & Perlmutter, A. P. (1999) · Cancer · doi:10.1002/(sici)1097-0142(19990315)85:6 · Cited by 50
The Bioidentical Hormone Debate: Are Bioidentical Hormones (Estradiol, Estriol, and Progesterone) Safer or More Efficacious than Commonly Used Synthetic Versions in Hormone Replacement Therapy?
Holtorf, K. (2009) · Postgraduate Medicine · doi:10.3810/pgm.2009.01.1949 · Cited by 71
Estrogens for Prevention of Coronary Heart Disease
Rossouw, J. E. (1996) · Circulation · doi:10.1161/01.cir.94.11.2982 · Cited by 71
Induction of Endothelial Nitric-oxide Synthase Phosphorylation by the Raloxifene Analog LY117018 Is Differentially Mediated by Akt and Extracellular Signal-regulated Protein Kinase in Vascular Endothelial Cells
Hisamoto, K., Ohmichi, M., Kanda, Y., Adachi, K., Nishio, Y., Hayakawa, J., Mabuchi, S., Takahashi, K., Tasaka, K., Miyamoto, Y., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103853200 · Cited by 72
Chapter 8: The SPECTRUM Population Model of the Impact of Screening and Treatment on U.S. Breast Cancer Trends From 1975 to 2000: Principles and Practice of the Model Methods
Mandelblatt, J. S., Schechter, C. B., Lawrence, W., Yi, B., & Cullen, J. C. (2006) · JNCI Monographs · doi:10.1093/jncimonographs/lgj008 · Cited by 70
The risk of breast cancer following reproductive surgery
Kreiger, N., Sloan, M., Cotterchio, M., & Kirsh, V. A. (1999) · European Journal of Cancer · doi:10.1016/s0959-8049(98)00343-8 · Cited by 70
Glutathione S-transferase class mu deletion polymorphism and breast cancer: results from prevalent versus incident cases.
Kelsey, K. T., Hankinson, S. E., Colditz, G. A., Springer, K., García‐Closas, M., Spiegelman, D. L., Manson, J. E., Garland, M., Stampfer, M. J., Willett, W. C., et al. (1997) · PubMed · Cited by 70
Bisphosphonates in bone diseases.
Sparidans, R. W., Twiss, I. M., & Talbot, S. (1998) · Pharmacy World & Science · doi:10.1023/a:1008626026484 · Cited by 69
Estrogen‐eluting, phosphorylcholine‐coated stent implantation is associated with reduced neointimal formation but no delay in vascular repair in a porcine coronary model
New, G., Moses, J. W., Roubin, G. S., Leon, M. B., Colombo, A., Iyer, S. S., Tio, F. O., Mehran, R., & Kipshidze, N. N. (2002) · Catheterization and Cardiovascular Interventions · doi:10.1002/ccd.10339 · Cited by 71
“The systemic use of this hormone is limited by the possible hyperplastic effects of estrogen on the uterus and breast in women [25], and also by the feminizing effects in males.”
Background
Prevention of Hormone-Related Cancers: Breast Cancer
Dunn, B. K., Wickerham, D. L., & Ford, L. G. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.08.028 · Cited by 69
Transdermal delivery of drugs for the treatment of bone diseases
Ramachandran, C., & Fleisher, D. (2000) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(00)00062-4 · Cited by 68
Evaluation of oriental medicinal herbs for estrogenic and antiproliferative activities
Kang, S. C., Lee, C. M., Choi, H., Lee, J. H., Oh, J. S., Kwak, J. H., & Zee, O. P. (2006) · Phytotherapy Research · doi:10.1002/ptr.1987 · Cited by 67
“Existing estrogen replacement therapy using synthetic estrogens has some side effects that include a slight but significant increase in the risk of developing breast and endometrial cancer due to unselective estrogenic action (Colditz et al., 1995, 1992; Henderson et al., 1988; Bolton et al., 1998).”
Background
A Metabolite of Equine Estrogens, 4-Hydroxyequilenin, Induces DNA Damage and Apoptosis in Breast Cancer Cell Lines
Chen, Y., Liu, X., Pisha, E., Constantinou, A. I., Hua, Y., Shen, L., van Breemen, R. B., Elguindi, E. C., Blond, S. Y., Zhang, F., et al. (2000) · Chemical Research in Toxicology · doi:10.1021/tx990186j · Cited by 67
Ploidy differences between hormone‐ and chemical carcinogen–induced rat mammary neoplasms: Comparison to invasive human ductal breast cancer*
Li, J. J., Papa, D., Davis, M. F., Weroha, S. J., Aldaz, C. M., El‐Bayoumy, K., Ballenger, J., Tawfik, O. W., & Li, S. A. (2002) · Molecular Carcinogenesis · doi:10.1002/mc.10022 · Cited by 67

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: Colditz, Graham A.
Hankinson, Susan E.
Willett, Walter C.
Manson, JoAnn E.
Stampfer, Meir J.
Hennekens, Charles
Rosner, Bernard
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
DOI: 10.1056/nejm199506153322401
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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The use of estrogens and progestins and the risk of breast cancer in postmenopausal women.

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