Skip to main content
Log in

Bone Mineral Density and Endogenous Hormones and Risk of Breast Cancer in Postmenopausal Women (United States)

  • Published:
Cancer Causes & Control Aims and scope Submit manuscript

Abstract

Objective: This case–cohort study was designed to examine whether total hip bone mineral density (BMD) is independently associated with breast cancer over and above its association with other determinants, including levels of total and bioavailable estradiol and testosterone and sex-hormone binding globulin. Methods: Our study population was selected from a cohort of 8203 postmenopausal women who were screened for the Fracture Intervention Trial in 1992, at which time BMD was assessed, and blood samples were obtained. A total of 109 women developed breast cancer during four years of follow-up; 173 other randomly selected women from the larger cohort were also selected. Cox proportional hazards with robust variance adjustment was used for these analyses. Results: Relative to women in the lower fourth of the BMD distribution, the risk associated with being in the upper fourth was 2.6 (95% confidence interval (CI) 1.1–5.8). After adjusting for serum hormone levels, the corresponding relative risk was 2.5 (95% CI 0.9–5.2). With body mass index and number of years since menopause added to the multivariate analysis, the relative risk decreased to 1.4 (95% CI 0.5–4.0).Conclusions: BMD may not influence breast cancer risk independent of its relationship with endogenous hormones and measured covariates.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Kosary CL, Ries AG, Miller BA, Hankey BF, Harvas A, Edwards BK (eds) (1995) SEER Cancer Statistics Review, 1973-1992: Tables and Graphs, National Cancer Institute. Bethesda MD: NIH Publ. No.96-2789.

  2. Kelsey JL (1993) Breast cancer epidemiology: summary and future directions. Epidemiol Rev 15: 256-263.

    Google Scholar 

  3. Thomas DB (1984) Do hormones cause breast cancer? Cancer 53: 595-604.

    Google Scholar 

  4. Selby C (1990) Sex hormone binding globulin: origin, function and clinical significance. Ann Clin Biochem 27: 532-541.

    Google Scholar 

  5. Thomas HV, Reeves GK, Key TJA (1997). Endogenous estrogen and postmenopausal breast cancer: a quantitative review. Cancer Causes Control 8: 922-928.

    Google Scholar 

  6. Bernstein L, Ross RK, Pike MC, Brown JB, Henderson BE (1990) Hormone levels in older women: a study of post-menopausal breast cancer patients and healthy population controls. Br J Cancer 61: 298-302.

    Google Scholar 

  7. Bruning PF, Bonfrer JMG, Hart AAM (1985) Non-protein bound oestradiol, sex hormone binding globulin, breast cancer and breast cancer risk. Br J Cancer 51: 479-484.

    Google Scholar 

  8. Jones LA, Ota DM, Jackson GA, et al. (1987) Bioavailability of estradiol as a marker for breast cancer risk assessment. Cancer Res 47: 5224-5229.

    Google Scholar 

  9. Ota DM, Jones LA, Jackson GL, Jackson PM, Kemp K, Bauman D (1986) Obesity, non-protein-bound estradiol levels, and distribution of estradiol in sera of breast cancer patients. Cancer 57: 558-562.

    Google Scholar 

  10. Toniolo PG, Levitz M, Zeleniuch-Jacquotte A, et al. (1995) A prospective study of endogenous estrogens and breast cancer in postmenopausal women. J Natl Cancer Inst 87: 190-197.

    Google Scholar 

  11. Hankinson SE, Willet WC, Manson JE, et al. (1998) Plasma sex steroid hormone levels and risk of breast cancer in postmenopausal women. J Natl Cancer Inst 90: 1292-1299.

    Google Scholar 

  12. Cauley JA, Lucas FL, Kuller LH, Stone K, Browner W, Cummings SR (1999) Elevated serum estradiol and testosterone concentrations are associated with a high risk of breast cancer. Ann Intern Med 130: 270-277.

    Google Scholar 

  13. Zeleniuch-Jacquotte A, Bruning PF, Bonfrer JMG, et al. (1997) Relation of serum levels of testosterone and dehydroepiandroster-one sulfate to risk of breast cancer in postmenopausal women. Am J Epidemol 145: 1030-1038.

    Google Scholar 

  14. Dorgan JF, Longcope C, Stephenson HE, et al. (1996) Relation of prediagnostic serum estrogen and androgen levels to breast cancer risk. Cancer Epidemiol Biomarkers Prev 5: 533-539.

    Google Scholar 

  15. Berrino F, Muti P, Micheli A, et al. (1996) Serum sex hormone levels after menopause and subsequent breast cancer. J Natl Cancer Inst 88: 291-296.

    Google Scholar 

  16. Wysowski DK, Comstock GW, Helsing KJ, Lau HL (1987) Sex hormone levels in serum in relation to the development of breast cancer. Am J Epidemiol 125: 791-799.

    Google Scholar 

  17. Helzlsouer KJ, Alberg AJ, Bush TL, Longcope C, Gordon GB, Comstock GW (1994) A prospective study of endogenous hor-mones and breast cancer. Cancer Detection Prev 18: 79-85.

    Google Scholar 

  18. Garland CF, Friedlander NJ, Barrett-Connor E, Khaw KT (1992) Sex hormones and postmenopausal breast cancer: a prospective study in an adult community. Am J Epidemiol 135: 1220-1230.

    Google Scholar 

  19. Kuller LH, Gutai JP (1995) Re: A prospective study of endogenous estrogens and breast cancer in postmenopausal women. J Natl Cancer Inst 87: 1414.

    Google Scholar 

  20. Cauley JA, Gutai JP, Kuller LH, et al. (1988) Endogenous estrogen levels and calcium intakes in postmenopausal women: relationships with cortical bone measures. JAMA 260: 3150-3155.

    Google Scholar 

  21. Murphy S, Khaw KT, Sneyd MJ, Compston JE (1992) Endoge-nous sex hormones and bone mineral density among community-based postmenopausal women. Postgrad Med J 68: 908-913.

    Google Scholar 

  22. Slemenda C, Hui SL, Longcope C, Johnston CC (1987) Sex steroid and bone mass. A study of changes about the time of menopause. J Clin Invest 80: 1261-1269.

    Google Scholar 

  23. Van Hemert AM, Birkenhager JC, DeJong FH, Vandenbroucke JP, Valkenburg HA (1989) Sex hormone binding globulin in postmenopausal women: a predictor of osteoporosis superior to endogenous oestrogens. Clin Endocrinol Oxf 31: 499-509.

    Google Scholar 

  24. Cauley JA, Frances LL, Kuller LH, Vogt MT, Browner WS, Cummings SR (1996) Bone mineral density and risk of breast cancer in older women. The Study of the Osteoporotic Fractures. JAMA 276: 1404-1408.

    Google Scholar 

  25. Zhang Y, Kiel DP, Kreger BE, et al. (1997) Bone mass and the risk of breast cancer among postmenopausal women. N Engl J Med 336: 611-617.

    Google Scholar 

  26. Buist DSM, LaCroix AZ, Barlow WE, White E, Weiss NS (2000) Bone mineral density and breast cancer risk in postmenopausal women. J Clin Epidemiol (In press).

  27. Black DM, Reiss TF, Nevitt MC, Cauley J, Karpf D, Cummings SR (1993) Design of the Fracture Intervention Trial. Osteoporosis Int 3: S29-S39.

    Google Scholar 

  28. Barlow WE, Ichikawa L, Rosner D, Izumi S (1999) Analysis of case-cohort designs. J Clin Epidemiol 52: 1165-1172.

    Google Scholar 

  29. SAS Version 6.12. Cary, NC: SAS Institute, Inc.

  30. Wu CH, Lundy LE (1971) Radioimmunoassay of plasma estro-gens. Steroids 18: 91-111.

    Google Scholar 

  31. Mayes DM, Nugent CA (1968) Determination of plasma testos-terone by the use of competitive protein binding. J Clin Endocrinol Metab 28: 1169-1176.

    Google Scholar 

  32. Cox DR, Oakes D (1984) Analysis of Survival Data. London: Chapman & Hall.

    Google Scholar 

  33. StataCorp (1997) Stata Statistical Software: Release 5.0. College Station, TX: Stata Corporation.

  34. Drafta D, Schindler AE, Milcu SM, et al. (1980) Plasma hormones in pre-and postmenopausal breast cancer. J Steroid Biochem 13: 793-802.

    Google Scholar 

  35. Meema S, Meema HE (1966) Possible estrogenic effect on bone in postmenopausal patients with mammary carcinoma. Cancer 19: 433-436.

    Google Scholar 

  36. Cauley JA, Gutai JP, Kuller KH, Powel JG (1991) Reliability and interrelations among serum sex hormones in postmenopausal women. Am J Epidemiol 133: 50-57.

    Google Scholar 

  37. Hankinson SE, Manson JE, Spiegelman D, Willet WC, Longcope C, Speizer FE (1995) Reproducibility of plasma hormone levels in postmenopausal women over a 2-3 year period. Cancer Epidemiol Biomarkers Prev 4: 649-654.

    Google Scholar 

  38. Kuller LH, Gutai JP, Meilahn E, Matthews KA, Plantinga P (1990) Relationship of endogenous sex steroid hormones to lipids and apoproteins in postmenopausal women. Arteriosclerosis 10: 1058-1066.

    Google Scholar 

  39. Siiteri PK, Murai JT, Hammond GL, Nisker JA, Raymoure WJ, Kuhn RW (1982) The serum transport of steroid hormones. Recent Prog Horm Res 38: 457-510.

    Google Scholar 

  40. Kuller LH (1995) The etiology of breast cancer-from epidemiology to prevention. Public Health Rev 23: 157-213.

    Google Scholar 

  41. Cauley JA, Gutai JP, Kuller LH, LeDonne D, Powell JG (1989) The epidemiology of serum sex hormones in postmenopausal women. Am J Epidemiol 129: 1120-1131.

    Google Scholar 

  42. Kleerekoper M, Nelson DA, Peterson EL, Wilson PS, Jacobsen G, Longcope C (1994) Body composition and gonadal steroids in older white and black women. J Clin Endocrinol Metab 79: 775-779.

    Google Scholar 

  43. Cummings SR, Kelsey JL, Nevitt MC, O'Dowd KJ (1985) Epidemiology of osteoporosis and osteoporotic fractures. Epidem-iol Rev 7: 178-208.

    Google Scholar 

  44. Salamone LM, Glynn NW, Black DM, et al. (1996) Determinants of premenopausal bone mineral density: the interplay of genetics and lifestyle factors. J Bone Miner Res 11: 1557-1565.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Diana S.M. Buist.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Buist, D.S., LaCroix, A.Z., Barlow, W.E. et al. Bone Mineral Density and Endogenous Hormones and Risk of Breast Cancer in Postmenopausal Women (United States). Cancer Causes Control 12, 213–222 (2001). https://doi.org/10.1023/A:1011231106772

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1011231106772

Navigation