© 1995 by Oxford University Press
Journal of the National Cancer Institute, Vol. 87, No. 3, 190-197,
February 1995
© 1995 Oxford University Press
A Prospective Study of Endogenous Estrogens and Breast Cancer in Postmenopausal Women
Affiliations of authors: Department of Environmental Medicine, New York University School of Medicine New York
Department of Obstetrics and Gynecology, New York University School of Medicine
The Gunman Breast Diagnostic Institute New York, N.Y.
Correspondence to: Paolo G. Toniolo, M.D., Department of Environmental Medicine, New York University School of Medicine, 341 East 25th St., New York, NY 10010.
Background: Circumstantial evidence links endogenous estrogens to increased risk of breast cancer in women, but direct epidemiologic support is limited. In particular, only a few small prospective studies have addressed this issue. Purpose: Our purpose was to assess breast cancer risk in relation to circulating levels of the two major endogenous estrogens, estrone and estradiol, measured before the clinical onset of the disease. Methods: The association between serum levels of estrogens and the risk of breast cancer was examined in a prospective cohort study of 14 291 New York City women, 35–65 years of age, who received screening for breast cancer at the time of blood sampling and who had not been diagnosed with breast cancer. During the first 5
years of study, we identified 130 breast cancers among the postmenopausal group (7063 women, 35 509 person-years). The case subjects and twice as many postmenopausal control subjects were included in a case-control study nested within the cohort. Biochemical analyses for percent free estradiol, percent estradiol bound to sex hormone-binding globulin (SHBG), total estradiol, estrone, and follicle-stimulating hormone were performed on sera that had been kept at –80°C since sampling. Results: For increasing quar-tiles of total estradiol, the odds ratio (ORs) of breast cancer, as adjusted for Quetelet index (weight in kilograms divided by the square of the height in meters), were 1.0, 0.9, 1.8, and 1.8 (P value for trend =.06); the ORs for increasing quar-tiles of estrone were 1.0, 2.2, 3.7, and 2.5 (P value for trend =.06). For increasing quartiles of free estradiol, defined as the fraction of estradiol that is not bound to proteins, the Quetelet index-adjusted ORs of breast cancer were 1.0, 1.4,
3.0, and 2.9 (P value for trend <.01). When we considered the percent of estradiol bound to SHBG, the Quetelet index-adjusted ORs were 1.0, 0.70, 0.40, and 0.32 (P value for trend <.01), thus suggesting a strong protective effect. These associations persisted or became even stronger when analyses were restricted to women whose samples had been drawn 2 or more years before breast cancer diagnosis. Conclusions: These data represent the first confirmation in a large prospective epidemiologic study of a link between circulating estrogens and breast cancer risk. Although estrogen levels appeared to fall within the conventional limits of normality in all women under study, those who subsequently developed breast cancer tended to show higher levels of estrone, total estradiol, and free estradiol, and a lower percent of estradiol bound to SHBG than women who remained free of cancer. Implications: Factors that increase endogenous estrogen production or reduce the binding of estradiol to SHBG may increase a woman‘s risk of developing breast cancer later in life. [J Natl Cancer Inst 87: 190–197, 1995]
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M. Kabuto, S. Akiba, R. G. Stevens, K. Neriishi, and C. E. Land A Prospective Study of Estradiol and Breast Cancer in Japanese Women Cancer Epidemiol. Biomarkers Prev., June 1, 2000; 9(6): 575 - 579. [Abstract] [Full Text]
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A. M. Duncan, B. E. Merz-Demlow, X. Xu, W. R. Phipps, and M. S. Kurzer Premenopausal Equol Excretors Show Plasma Hormone Profiles Associated with Lowered Risk of Breast Cancer Cancer Epidemiol. Biomarkers Prev., June 1, 2000; 9(6): 581 - 586. [Abstract] [Full Text]
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B. E. Henderson and H. S. Feigelson Hormonal carcinogenesis Carcinogenesis, March 1, 2000; 21(3): 427 - 433. [Abstract] [Full Text] [PDF]
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C. Guillemette, R. C. Millikan, B. Newman, and D. E. Housman Genetic Polymorphisms in Uridine Diphospho-Glucuronosyltransferase 1A1 and Association with Breast Cancer among African Americans Cancer Res., February 1, 2000; 60(4): 950 - 956. [Abstract] [Full Text]
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C. S. Healey, A. M. Dunning, F. Durocher, D. Teare, P. D.P. Pharoah, R. N. Luben, D. F. Easton, and B. A.J. Ponder Polymorphisms in the human aromatase cytochrome P450 gene (CYP19) and breast cancer risk Carcinogenesis, February 1, 2000; 21(2): 189 - 193. [Abstract] [Full Text] [PDF]
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D. S. Michaud, J. E. Manson, D. Spiegelman, R. L. Barbieri, D. W. Sepkovic, H. L. Bradlow, and S. E. Hankinson Reproducibility of Plasma and Urinary Sex Hormone Levels in Premenopausal Women over a One-Year Period Cancer Epidemiol. Biomarkers Prev., December 1, 1999; 8(12): 1059 - 1064. [Abstract] [Full Text]
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X. Xu, A. M. Duncan, B. E. Merz-Demlow, W. R. Phipps, and M. S. Kurzer Menstrual Cycle Effects on Urinary Estrogen Metabolites J. Clin. Endocrinol. Metab., November 1, 1999; 84(11): 3914 - 3918. [Abstract] [Full Text]
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S. A. Khan, A. Sachdeva, S. Naim, M. M. Meguid, W. Marx, H. Simon, J. D. Halverson, and P. J. Numann The Normal Breast Epithelium of Women with Breast Cancer Displays an Aberrant Response to Estradiol Cancer Epidemiol. Biomarkers Prev., October 1, 1999; 8(10): 867 - 872. [Abstract] [Full Text]
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T. Thomas Individualized Testing and Outcome Measurements Are Needed for Successful Hormone Replacement Therapy J. Clin. Endocrinol. Metab., October 1, 1999; 84(10): 3852 - 3853. [Full Text] [PDF]
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S. R. Cummings, S. Eckert, K. A. Krueger, D. Grady, T. J. Powles, J. A. Cauley, L. Norton, T. Nickelsen, N. H. Bjarnason, M. Morrow, et al. The Effect of Raloxifene on Risk of Breast Cancer in Postmenopausal Women: Results From the MORE Randomized Trial JAMA, June 16, 1999; 281(23): 2189 - 2197. [Abstract] [Full Text] [PDF]
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A. McTiernan, R. S. Schwartz, J. Potter, and D. Bowen Exercise Clinical Trials in Cancer Prevention Research:A Call to Action Cancer Epidemiol. Biomarkers Prev., March 1, 1999; 8(3): 201 - 207. [Abstract] [Full Text] [PDF]
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J. A. Cauley, F. L. Lucas, L. H. Kuller, K. Stone, W. Browner, S. R. Cummings, and for the Study of Osteoporotic Fractures Research G Elevated Serum Estradiol and Testosterone Concentrations Are Associated with a High Risk for Breast Cancer Ann Intern Med, February 16, 1999; 130(4_Part_1): 270 - 277. [Abstract] [Full Text] [PDF]
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S. R. Cummings, W. S. Browner, D. Bauer, K. Stone, K. Ensrud, S. Jamal, B. Ettinger, and The Study of Osteoporotic Fractures Research Group Endogenous Hormones and the Risk of Hip and Vertebral Fractures among Older Women N. Engl. J. Med., September 10, 1998; 339(11): 733 - 738. [Abstract] [Full Text] [PDF]
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A. McTiernan Exercise and Breast Cancer -- Time to Get Moving? N. Engl. J. Med., May 1, 1997; 336(18): 1311 - 1312. [Full Text]
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R. Ballard-Barbash, D. F. Birt, M. Kestin, and I. B. King Perspectives on Integrating Experimental and Epidemiologic Research on Diet, Anthropometry and Breast Cancer J. Nutr., May 1, 1997; 127 (5): 936S - 936S. [Abstract] [Full Text] [PDF]
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Y. Zhang, D. P. Kiel, B. E. Kreger, L. A. Cupples, R. C. Ellison, J. F. Dorgan, A. Schatzkin, D. Levy, and D. T. Felson Bone Mass and the Risk of Breast Cancer among Postmenopausal Women N. Engl. J. Med., February 27, 1997; 336(9): 611 - 617. [Abstract] [Full Text] [PDF]
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J. A. Cauley, F. L. Lucas, L. H. Kuller, M. T. Vogt, W. S. Browner, and S. R. Cummings Bone Mineral Density and Risk of Breast Cancer in Older Women: The Study of Osteoporotic Fractures JAMA, November 6, 1996; 276(17): 1404 - 1408. [Abstract] [PDF]
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C. Campagnoli, N. Biglia, and P. Sismondi Hormone Replacement Therapy and Breast Cancer Risk JAMA, April 17, 1996; 275(15): 1159 - 1159. [Abstract] [PDF]
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H.-O. Adami and I. Persson Hormone Replacement and Breast Cancer: A Remaining Controversy? JAMA, July 12, 1995; 274(2): 178 - 179. [Abstract] [PDF]
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