Skip to main content
Log in

Risks of breast and endometrial cancer after estrogen and estrogen–progestin replacement

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

Abstract

Objective: We studied the risk of breast and endometrial cancer in a cohort of 11,231 Swedish women prescribed different replacement hormone regimens.

Methods: All 10,472 women at risk of developing breast cancer and 8,438 women at risk of endometrial cancer were followed up from the time of the questionnaire in 1987–88 through 1993, by record-linkages to the National Swedish Cancer Registry. Using data from a questionnaire we analyzed the relationships between hormone exposures and cancer risk, with non-compliers and users of less than 1 year as a reference group.

Results: For breast cancer, women reporting use of estrogens combined with progestins had evidence of an increased risk relative to women denying intake or taking hormones for less than 1 year; relative risk (RR) = 1.4 (95% confidence interval 0.9–2.3) after 1–6 years of intake, and RR=1.7 (95% CI 1.1–2.6) after more than 6 years. This excess risk seemed confined to recent exposure. We found no association with intake of estrogens alone using non-compliers and short-term takers as the reference group. The risk of invasive endometrial cancer was increased four-fold in women using medium-potency estrogens alone for 6 years or longer, RR = 4.2 (95% CI 2.5–8.4). Women on such long-term progestin-combined treatment had a lower, non-significant, excess risk (RR = 1.4; 95% CI 0.6–3.3).

Conclusions: We conclude that long-term recent use of estrogen–progestin combined replacement therapy may increase the risk of breast cancer. Exposure to estrogen alone substantially elevates the risk of endometrial cancer, an increase that can be reduced or perhaps avoided by adding progestins.

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.

Institutional subscriptions

Similar content being viewed by others

References

  1. Daly E, Gray A, Barlow D, McPherson K, Roche M, Vessey M (1993) Measuring the impact of menopausal symptoms on quality of life. BMJ 307: 836-840.

    Google Scholar 

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

    Google Scholar 

  3. Stampfer MJ, Colditz GA (1991) Estrogen replacement therapy and coronary heart disease: a quantitative assessment of the epidemiologic evidence. Prev Med 20: 47-63.

    Google Scholar 

  4. Bergkvist L, Adami HO, Persson I, Hoover R, Schairer C (1989) The risk of breast cancer after estrogen and estrogen-progestin replacement. N Engl J Med 321: 293-297.

    Google Scholar 

  5. Yang CP, Daling JR, Band PR, Gallagher RP, White E, Weiss NS (1992) Noncontraceptive hormone use and risk of breast cancer. Cancer Causes Control 3: 475-479.

    Google Scholar 

  6. Ewertz M (1988) Influence of non-contraceptive exogenous and endogenous sex hormones on breast cancer risk in Denmark. Int J Cancer 42: 832-838.

    Google Scholar 

  7. Hunt K, Vessey M, McPherson K, Coleman M (1987) Long-term surveillance of mortality and cancer incidence in women receiving hormone replacement therapy. Br J Obstet Gynaecol 94: 620-635.

    Google Scholar 

  8. Colditz GA, Hankinson SE, Hunter DJ, et al. (1995) The use of estrogens and progestins and the risk of breast cancer in postmenopausal women. N Engl J Med 332: 1589-1593.

    Google Scholar 

  9. Mills PK, Beeson WL, Phillips RL, Fraser GE (1989) Prospective study of exogenous hormone use and breast cancer in Seventh-day Adventists. Cancer 64: 591-597.

    Google Scholar 

  10. Persson I, Yuen J, Bergkvist L, Schairer C (1996) Cancer incidence and mortality in women receiving estrogen and estrogen-progestin replacement therapy — long-term follow-up of a Swedish cohort. Int J Cancer 67: 327-332.

    Google Scholar 

  11. Collaborative Group on Hormonal Factors in Breast Cancer (1997) Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52 705 women with breast cancer and 108 411 women without breast cancer. Lancet 350: 1047-1059.

    Google Scholar 

  12. Persson I, Thurfjell E, Bergström R, Holmberg L (1997) Hormone replacement therapy and the risk of breast cancer. Nested case-control study in a cohort of Swedish women attending mammography screening. Int J Cancer 72: 758-761.

    Google Scholar 

  13. Newcomb PA, Longnecker MP, Storer BE, et al. (1995) Long-term hormone replacement therapy and risk of breast cancer in postmenopausal women. Am J Epidemiol 142: 788-795.

    Google Scholar 

  14. Stanford JL, Weiss NS, Voigt LF, Daling JR, Habel LA, Rossing MA (1995) Combined estrogen and progestin hormone replacement therapy in relation to risk of breast cancer in middle-aged women. JAMA 274: 137-142.

    Google Scholar 

  15. Schuurman AG, van den Brandt PA, Goldbohm RA (1995) Exogenous hormone use and the risk of postmenopausal breast cancer: results from The Netherlands Cohort Study. Cancer Causes Control 6: 416-424.

    Google Scholar 

  16. Schairer C, Byrne C, Keyl PM, Brinton LA, Sturgeon SR, Hoover RN (1994) Menopausal estrogen and estrogen-progestin replacement therapy and risk of breast cancer (United States). Cancer Causes Control 5: 491-500.

    Google Scholar 

  17. Grady D, Gebretsadik T, Kerlikowske K, Ernster V, Petitti D (1995) Hormone replacement therapy and endometrial cancer risk: a meta-analysis. Obstet Gynecol 85: 304-313.

    Google Scholar 

  18. Shapiro JA, Weiss NS, Beresford SA, Voigt LF (1998) Menopausal hormone use and endometrial cancer, by tumor grade and invasion. Epidemiology 9: 99-101.

    Google Scholar 

  19. Brinton LA, Hoover RN (1993) Estrogen replacement therapy and endometrial cancer risk: unresolved issues. The Endometrial Cancer Collaborative Group. Obstet Gynecol 81: 265-271.

    Google Scholar 

  20. Persson I, Adami HO, Bergkvist L, et al. (1989) Risk of endometrial cancer after treatment with oestrogens alone or in conjunction with progestogens: results of a prospective study. BMJ 298: 147-151.

    Google Scholar 

  21. Voigt LF, Weiss NS, Chu J, Daling JR, McKnight B, van Belle G (1991) Progestagen supplementation of exogenous oestrogens and risk of endometrial cancer. Lancet 338: 274-277.

    Google Scholar 

  22. Jick SS, Walker AM, Jick H (1993) Estrogens, progesterone, and endometrial cancer. Epidemiology 4: 20-24.

    Google Scholar 

  23. Beresford SA, Weiss NS, Voigt LF, McKnight B (1997) Risk of endometrial cancer in relation to use of oestrogen combined with cyclic progestagen therapy in postmenopausal women. Lancet 349: 458-461.

    Google Scholar 

  24. Pike MC, Peters RK, Cozen W, et al. (1997) Estrogen-progestin replacement therapy and endometrial cancer. J Natl Cancer Inst 89: 1110-1116.

    Google Scholar 

  25. Persson I, Adami HO, Johansson E, Lindberg B, Manell P, Westerholm B (1983) Cohort study of oestrogen treatment and the risk of endometrial cancer: evaluation of method and its applicability. Eur J Clin Pharmacol 25: 625-632.

    Google Scholar 

  26. National Board of Health and Welfare. Stockholm (1996) Official Statistics of Sweden.

  27. MCullagh P, Nelder J (1989) In: MCullagh P, Nelder J, eds Generalized Linear Models. London: Chapman & Hall.

    Google Scholar 

  28. Persson I, Bergkvist L, Lindgren C, Yuen J (1997) Hormone replacement therapy and major risk factors for reproductive cancers, osteoporosis, and cardiovascular diseases: evidence of confounding by exposure characteristics. J Clin Epidemiol 50: 611-618.

    Google Scholar 

  29. Nyström L, Rutqvist LE, Wall S, et al. (1993) Breast cancer screening with mammography: overview of Swedish randomised trials. Lancet 341: 973-978.

    Google Scholar 

  30. Persson I, Thurfjell E, Holmberg L (1997) Effect of estrogen and estrogen-progestin replacement regimens on mammographic breast parenchymal density. J Clin Oncol 15: 3201-3207.

    Google Scholar 

  31. Laya MB, Larson EB, Taplin SH, White E (1996) Effect of estrogen replacement therapy on the specificity and sensitivity of screening mammography. J Natl Cancer Inst 88: 643-649.

    Google Scholar 

  32. Pike MC, Spicer DV, Dahmoush L, Press MF (1993) Estrogens, progestogens, normal breast cell proliferation, and breast cancer risk. Epidemiol Rev 15: 17-35.

    Google Scholar 

  33. Key TJ, Pike MC (1988) The dose-effect relationship between “unopposed” oestrogens and endometrial mitotic rate: its central role in explaining and predicting endometrial cancer risk. Br J Cancer 57: 205-212.

    Google Scholar 

  34. Cline JM, Söderqvist G, von Schoultz E, Skoog L, von Schoultz B (1996) Effects of hormone replacement therapy on the mammary gland of surgically postmenopausal cynomolgus macaques. Am J Obstet Gynecol 174: 93-100.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Persson, I., Weiderpass, E., Bergkvist, L. et al. Risks of breast and endometrial cancer after estrogen and estrogen–progestin replacement. Cancer Causes Control 10, 253–260 (1999). https://doi.org/10.1023/A:1008909128110

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1008909128110

Navigation