Cancer Causes & Control

, Volume 18, Issue 8, pp 847–852 | Cite as

Declines in breast cancer after the WHI: apparent impact of hormone therapy

  • Christina A. ClarkeEmail author
  • Sally L. Glaser
Original Paper


Large numbers of US women stopped taking hormone therapies (HT), especially estrogen/progestin (EP) formulations, after the Women’s Health Initiative trial detected elevated risks of breast cancer in EP users and was halted in July 2002. Recent reports have indicated substantial and significant declines in population-based breast cancer incidence, particularly hormone-sensitive forms, for 2003 and 2004. Are these events linked? This commentary considers the available evidence linking the mass cessation of HT in 2002 to the breast cancer incidence declines of 2003/2004 and quantifies the potential impact of the cessation on the overall burden of breast cancer in the US.


Breast cancer Incidence time trends Hormone therapy Estrogen/progestin Population attributable fraction 



The authors acknowledge Drs. Marcia Stefanick, Alice Whittemore, and Giske Ursin for their helpful comments. The collection of cancer incidence data used in this study was supported by the California Department of Health Services as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute’s Surveillance, Epidemiology and End Results Program under contract N01-PC-35136 awarded to the Northern California Cancer Center, contract N01-PC-35139 awarded to the University of Southern California, and contract N02-PC-15105 awarded to the Public Health Institute; and the Centers for Disease Control and Prevention’s National Program of Cancer Registries, under agreement U55/CCR921930-02 awarded to the Public Health Institute. The ideas and opinions expressed herein are those of the authors and endorsement by the State of California, Department of Health Services, the National Cancer Institute, and the Centers for Disease Control and Prevention or their contractors and subcontractors is not intended nor should be inferred. Dr. Clarke has served as an expert witness for plaintiff lawyers preparing hormone therapy litigation.


  1. 1.
    Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML et al (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the women’s health initiative randomized controlled trial. Jama 288(3):321–333PubMedCrossRefGoogle Scholar
  2. 2.
    Colditz GA (2005) Estrogen, estrogen plus progestin therapy, and risk of breast cancer. Clin Cancer Res 11(2 Pt 2):909s–917sPubMedGoogle Scholar
  3. 3.
    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(5):293–297PubMedCrossRefGoogle Scholar
  4. 4.
    Kolata G, Peterson M (2002) Hormone replacement study a shock to the medical system. New York Times 2002 July 10Google Scholar
  5. 5.
    Hersh AL, Stefanick ML, Stafford RS (2004) National use of postmenopausal hormone therapy: annual trends and response to recent evidence. Jama 291(1):47–53PubMedCrossRefGoogle Scholar
  6. 6.
    Ravdin PM, Cronin KA, Howlader N, Chlebowski RT, Berry DA (2006) A sharp decrease in breast cancer incidence in the United States in 2003. Breast Cancer Res Treat 100(Suppl 1):S6Google Scholar
  7. 7.
    Howe HL, Wu X, Ries LA, Cokkinides V, Ahmed F, Jemal A et al (2006) Annual report to the nation on the status of cancer, 1975–2003, featuring cancer among US Hispanic/Latino populations. Cancer 107(8):1711–1742PubMedCrossRefGoogle Scholar
  8. 8.
    Clarke CA, Glaser SL, Uratsu CS, Selby JV, Kushi LH, Herrinton LJ (2006) Recent declines in hormone therapy utilization and breast cancer incidence: clinical and population-based evidence. J Clin Oncol 24(33):e49–e50PubMedCrossRefGoogle Scholar
  9. 9.
    Ravdin PM, Cronin KA, Howlader N, Berg CD, Chlebowski RT, Feuer EJ et al (2007) The decrease in breast-cancer incidence in 2003 in the United States. N Engl J Med 356(16):1670–1674PubMedCrossRefGoogle Scholar
  10. 10.
    Haas JS, Kaplan CP, Gerstenberger EP, Kerlikowske K (2004) Changes in the use of postmenopausal hormone therapy after the publication of clinical trial results. Ann Intern Med 140(3):184–188PubMedGoogle Scholar
  11. 11.
    Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs B et al (1998) Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. Jama 280(7):605–613PubMedCrossRefGoogle Scholar
  12. 12.
    Katalinic A, Rawal R (2007) Decline in breast cancer incidence after decrease in utilisation of hormone replacement therapy. Breast Cancer Res Treat. E-published on 24 April 2007Google Scholar
  13. 13.
    Robbins AS, Clarke CA (2007) Regional changes in hormone therapy use and breast cancer incidence, California, 2001–2004. J Clinic Oncol (in press)Google Scholar
  14. 14.
    Wysowski DK, Governale LA (2005) Use of menopausal hormones in the United States, 1992 through June, 2003. Pharmacoepidemiol Drug Saf 14(3):171–176PubMedCrossRefGoogle Scholar
  15. 15.
    Johnston M (2005) Breast cancer drop linked to fall in use of HRT. New Zealand Herald December 20, 2006, Sect. Accessed electronically at = 1&objectid = 10416198
  16. 16.
    Centers for Disease Control (2007) Use of mammograms among women aged < or = 40 years—United States, 2000–2005. MMWR Morb Mortal Wkly Rep 56(3):49–51Google Scholar
  17. 17.
    California Health Interview Survey (2007) CHIS public use files 2001, 2003, 2005. Available from [Cited, accessed January, 2007]Google Scholar
  18. 18.
    Jemal A, Ward E, Thun MJ (2007) Recent trends in breast cancer incidence rates by age and tumor characteristics among US women. Breast Cancer Res 9(3):R28PubMedCrossRefGoogle Scholar
  19. 19.
    Centers for Disease Control (2006) Behavioral risk factor surveillance systemGoogle Scholar
  20. 20.
    Dietel M, Lewis MA, Shapiro S (2005) Hormone replacement therapy: pathobiological aspects of hormone-sensitive cancers in women relevant to epidemiological studies on HRT: a mini-review. Hum Reprod 20(8):2052–2060PubMedCrossRefGoogle Scholar
  21. 21.
    Key TJ, Pike MC (1988) The role of oestrogens and progestagens in the epidemiology and prevention of breast cancer. Eur J Cancer Clin Oncol 24(1):29–43PubMedCrossRefGoogle Scholar
  22. 22.
    Pike MC (2005) The role of mammographic density in evaluating changes in breast cancer risk. Gynecol Endocrinol 21(Suppl 1):1–5PubMedCrossRefGoogle Scholar
  23. 23.
    Beral V (2003) Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet 362(9382):419–427PubMedCrossRefGoogle Scholar
  24. 24.
    Reeves GK, Beral V, Green J, Gathani T, Bull D (2006) Hormonal therapy for menopause and breast-cancer risk by histological type: a cohort study and meta-analysis. Lancet Oncol 7(11):910–918PubMedCrossRefGoogle Scholar
  25. 25.
    Austin DF, Roe KM (1979) Increase in cancer of the corpus uteri in the San Francisco-Oakland standard metropolitan statistical area, 1960–75. J Natl Cancer Inst 62(1):13–16PubMedGoogle Scholar
  26. 26.
    Weiss NS, Szekely DR, Austin DF (1976) Increasing incidence of endometrial cancer in the United States. N Engl J Med 294(23):1259–1262PubMedCrossRefGoogle Scholar
  27. 27.
    Smith DC, Prentice R, Thompson DJ, Herrmann WL (1975) Association of exogenous estrogen and endometrial carcinoma. N Engl J Med 293(23):1164–1167PubMedCrossRefGoogle Scholar
  28. 28.
    Austin DF, Roe KM (1982) The decreasing incidence of endometrial cancer: public health implications. Am J Public Health 72(1):65–68PubMedCrossRefGoogle Scholar
  29. 29.
    Glass AG, Hoover RN (1990) Rising incidence of breast cancer: relationship to stage and receptor status. J Natl Cancer Inst 82(8):693–696PubMedCrossRefGoogle Scholar
  30. 30.
    Clarke CA, Purdie DM, Glaser SL (2006) Population attributable risk of breast cancer in white women associated with immediately modifiable risk factors. BMC Cancer 6:170PubMedCrossRefGoogle Scholar
  31. 31.
    Chlebowski RT, Hendrix SL, Langer RD, Stefanick ML, Gass M, Lane D et al (2003) Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women’s Health Initiative Randomized Trial. Jama 289(24):3243–3253PubMedCrossRefGoogle Scholar
  32. 32.
    Anderson GL, Chlebowski RT, Rossouw JE, Rodabough RJ, McTiernan A, Margolis KL et al (2006) Prior hormone therapy and breast cancer risk in the Women’s Health Initiative randomized trial of estrogen plus progestin. Maturitas 55(2):103–115PubMedCrossRefGoogle Scholar
  33. 33.
    North American Association of Central Cancer Registries (2007) Cancer in North America (CINA + Online). Springfield, Illinois.
  34. 34.
    Coombs NJ, Taylor R, Wilcken N, Fiorica J, Boyages J (2005) Hormone replacement therapy and breast cancer risk in California. Breast J 11(6):410–415PubMedCrossRefGoogle Scholar
  35. 35.
    Food and Drug Administration. Prempro (NDA 020527) label and approval history, revisions 8/2002,1/2003,8/2004,1/2007., accessed 15 May 2007Google Scholar

Copyright information

© Springer Science + Business Media B.V. 2007

Authors and Affiliations

  1. 1.Northern California Cancer CenterFremontUSA
  2. 2.Stanford Comprehensive Cancer CenterStanfordUSA

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