Skip to main content

Advertisement

SpringerLink
Log in

Risk of breast cancer after stopping menopausal hormone therapy in the E3N cohort

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

An Erratum to this article was published on 03 August 2014

Abstract

Questions remain on how the excess risk of breast cancer associated with menopausal hormone therapy (MHT) evolves after treatment stops. We investigated that issue in the E3N cohort, with 3,678 invasive breast cancers identified between 1992 and 2008 among 78,353 women (881,290 person-years of postmenopausal follow-up). Exposure to MHT was assessed through biennial self-administered questionnaires and classified by type of progestagen component (progesterone or dydrogesterone; other progestagen), duration (short-term ≤5 years; long-term >5 years) and time since last use (current, 3 months-5 years, 5–10 years, 10+ years). Hazard ratios (HR) and confidence intervals (CI) were estimated with Cox models. Among short-term users, only those currently using estrogens associated with a progestagen other than progesterone/dydrogesterone had a significantly elevated breast cancer risk (HR 1.70, 95 % CI 1.50–1.91, compared with never users). Long-term use of this type of MHT was associated with a HR of 2.02 (1.81–2.26) when current and of 1.36 (1.13–1.64), 1.34 (1.04–1.73), and 1.52 (0.87–2.63) when stopped ≤5, 5–10, and 10+ years earlier, respectively. Our results suggest residual increases in breast cancer risk several years after MHT cessation, which are restricted to long-term treatments. Whether increases persist more than 10 years after cessation deserves continuing investigation.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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. Grosse Y, Baan R, Straif K, Secretan B, El Ghissassi F, Bouvard V, Benbrahim-Tallaa L, Guha N, Galichet L, Cogliano V, WHO International Agency for Research on Cancer Monograph Working Group (2009) A review of human carcinogens-part A: pharmaceuticals. Lancet Oncol 10:13–14

    Article  PubMed  Google Scholar 

  2. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J, Writing Group for the Women’s Health Initiative Investigators (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the women’s health initiative randomized controlled trial. JAMA 288:321–333

    Article  CAS  PubMed  Google Scholar 

  3. Beral V, Million Women Study Collaborators (2003) Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet 362:419–427

    Article  CAS  PubMed  Google Scholar 

  4. Ravdin PM, Cronin KA, Howlader N, Berg CD, Chlebowski RT, Feuer EJ, Edwards BK, Berry DA (2007) The decrease in breast-cancer incidence in 2003 in the United States. N Engl J Med 356:1670–1674

    Article  CAS  PubMed  Google Scholar 

  5. Ringa V, Fournier A (2008) Did the decrease in use of menopausal hormone therapy induce a decrease in the incidence of breast cancer in France (and elsewhere)? Rev Epidemiol Sante Publique 56:e8–e12

    Article  Google Scholar 

  6. Zbuk K, Anand SS (2012) Declining incidence of breast cancer after decreased use of hormone-replacement therapy: magnitude and time lags in different countries. J Epidemiol Community Health 66:1–7. doi:10.1136/jech.2008.083774

    Article  PubMed  Google Scholar 

  7. Collins JA, Blake JM, Crosignani PG (2005) Breast cancer risk with postmenopausal hormonal treatment. Hum Reprod Update 11:545–560

    Article  CAS  PubMed  Google Scholar 

  8. Chlebowski RT, Kuller LH, Prentice RL, Stefanick ML, Manson JE, Gass M, Aragaki AK, Ockene JK, Lane DS, Sarto GE, Rajkovic A, Schenken R, Hendrix SL, Ravdin PM, Rohan TE, Yasmeen S, Anderson G, WHI Investigators (2009) Breast cancer after use of estrogen plus progestin in postmenopausal women. N Engl J Med 360:573–587

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Fournier A, Berrino F, Clavel-Chapelon F (2008) Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. Breast Cancer Res Treat 107:103–111

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Fournier A, Fabre A, Mesrine S, Boutron-Ruault MC, Berrino F, Clavel-Chapelon F (2008) Use of different postmenopausal hormone therapies and risk of histology- and hormone receptor-defined invasive breast cancer. J Clin Oncol 26:1260–1268

    Article  PubMed Central  PubMed  Google Scholar 

  11. Fournier A, Mesrine S, Boutron-Ruault MC, Clavel-Chapelon F (2009) Estrogen-progestagen menopausal hormone therapy and breast cancer: does delay from menopause onset to treatment initiation influence risks? J Clin Oncol 27:5138–5143

    Article  PubMed  Google Scholar 

  12. 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

    Article  Google Scholar 

  13. Magnusson C, Baron JA, Correia N, Bergstrom R, Adami HO, Persson I (1999) Breast-cancer risk following long-term oestrogen- and oestrogen-progestin-replacement therapy. Int J Cancer 81:339–344

    Article  CAS  PubMed  Google Scholar 

  14. Schairer C, Lubin J, Troisi R, Sturgeon S, Brinton L, Hoover R (2000) Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk. JAMA 283:485–491

    Article  CAS  PubMed  Google Scholar 

  15. Brinton LA, Richesson D, Leitzmann MF, Gierach GL, Schatzkin A, Mouw T, Hollenbeck AR, Lacey JV Jr (2008) Menopausal hormone therapy and breast cancer risk in the NIH-AARP Diet and Health Study Cohort. Cancer Epidemiol Biomarkers Prev 17:3150–3160. doi:10.1158/1055-9965.EPI-08-0435

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Calle EE, Feigelson HS, Hildebrand JS, Teras LR, Thun MJ, Rodriguez C (2009) Postmenopausal hormone use and breast cancer associations differ by hormone regimen and histologic subtype. Cancer 115:936–945. doi:10.1002/cncr.24101

    Article  CAS  PubMed  Google Scholar 

  17. Saxena T, Lee E, Henderson KD, Clarke CA, West D, Marshall SF, Deapen D, Bernstein L, Ursin G (2010) Menopausal hormone therapy and subsequent risk of specific invasive breast cancer subtypes in the California Teachers Study. Cancer Epidemiol Biomarkers Prev 19:2366–2378. doi:10.1158/1055-9965.EPI-10-0162

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Beral V, Reeves G, Bull D, Green J, Million Women Study Collaborators (2011) Breast cancer risk in relation to the interval between menopause and starting hormone therapy. J Natl Cancer Inst 103:296–305. doi:10.1093/jnci/djq527

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Chlebowski RT, Manson JE, Anderson GL, Cauley JA, Aragaki AK, Stefanick ML, Lane DS, Johnson KC, Wactawski-Wende J, Chen C, Qi L, Yasmeen S, Newcomb PA, Prentice RL (2013) Estrogen plus progestin and breast cancer incidence and mortality in the Women’s Health Initiative Observational Study. J Natl Cancer Inst 105:526–535. doi:10.1093/jnci/djt043

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Racine A, Bijon A, Fournier A, Mesrine S, Clavel-Chapelon F, Carbonnel F, Boutron-Ruault MC (2013) Menopausal hormone therapy and risk of cholecystectomy: a prospective study based on the French E3N cohort. CMAJ 185:555–561. doi:10.1503/cmaj.121490

    Article  PubMed Central  PubMed  Google Scholar 

  21. Weiss LK, Burkman RT, Cushing-Haugen KL, Voigt LF, Simon MS, Daling JR, Norman SA, Bernstein L, Ursin G, Marchbanks PA, Strom BL, Berlin JA, Weber AL, Doody DR, Wingo PA, McDonald JA, Malone KE, Folger SG, Spirtas R (2002) Hormone replacement therapy regimens and breast cancer risk (1). Obstet Gynecol 100:1148–1158

    Article  CAS  PubMed  Google Scholar 

  22. Newcomb PA, Titus-Ernstoff L, Egan KM, Trentham-Dietz A, Baron JA, Storer BE, Willett WC, Stampfer MJ (2002) Postmenopausal estrogen and progestin use in relation to breast cancer risk. Cancer Epidemiol Biomarkers Prev 11:593–600

    CAS  PubMed  Google Scholar 

  23. Allen NE, Tsilidis KK, Key TJ et al (2010) Menopausal hormone therapy and risk of endometrial carcinoma among postmenopausal women in the European Prospective Investigation Into Cancer and Nutrition. Am J Epidemiol 172:1394–1403. doi:10.1093/aje/kwq300

    Article  PubMed  Google Scholar 

  24. Santen RJ (2002) To block estrogen’s synthesis or action: that is the question. J Clin Endocrinol Metab 87:3007–3012

    CAS  PubMed  Google Scholar 

  25. Banks E, Beral V, Cameron R, Hogg A, Langley N, Barnes I, Bull D, Elliman J, Harris CL (2001) Agreement between general practice prescription data and self-reported use of hormone replacement therapy and treatment for various illnesses. J Epidemiol Biostat 6:357–363

    Article  CAS  PubMed  Google Scholar 

  26. Sandini L, Pentti K, Tuppurainen M, Kroger H, Honkanen R (2008) Agreement of self-reported estrogen use with prescription data: an analysis of women from the Kuopio Osteoporosis Risk Factor and Prevention Study. Menopause 15:282–289

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors are indebted to all of the women in the cohort for providing the data used in the E3N study and to practitioners for providing pathology reports. They are grateful to Rafika Chaït, Lyan Hoang, Maryvonne Niravong, and Marie Fangon for their technical assistance. They also thank Jo-Ann Cahn for correcting and clarifying their English. This work was supported by a grant from the Institut de Recherche en Santé Publique (IReSP, call for research projects 2011 as part of the “Plan Cancer 2009–2013”). The E3N cohort is being studied with the financial support of the Mutuelle Générale de l’Education Nationale (MGEN); the European Community; the Ligue nationale contre le cancer; the Institut Gustave–Roussy; the Institut National de la Santé et de la Recherche Médicale (INSERM); and the Fondation de France.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Inserm, Center for Research in Epidemiology and Population Health, U1018, Nutrition, Hormones and Women’s Health Team, 94807, Villejuif, France

    Agnès Fournier, Sylvie Mesrine, Laure Dossus, Marie-Christine Boutron-Ruault & Françoise Clavel-Chapelon

  2. Univ Paris-Sud, UMRS 1018, 94807, Villejuif, France

    Agnès Fournier, Sylvie Mesrine, Laure Dossus, Marie-Christine Boutron-Ruault & Françoise Clavel-Chapelon

  3. Institut Gustave Roussy, 94805, Villejuif, France

    Agnès Fournier, Sylvie Mesrine, Laure Dossus, Marie-Christine Boutron-Ruault & Françoise Clavel-Chapelon

  4. Department of Obstetrics-Gynecology and Reproductive Medicine, APHP Hôpital Tenon, Univ. Pierre Et Marie Curie Paris 06, Paris, France

    Nathalie Chabbert-Buffet

Authors
  1. Agnès Fournier
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sylvie Mesrine
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Laure Dossus
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marie-Christine Boutron-Ruault
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Françoise Clavel-Chapelon
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nathalie Chabbert-Buffet
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Agnès Fournier.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fournier, A., Mesrine, S., Dossus, L. et al. Risk of breast cancer after stopping menopausal hormone therapy in the E3N cohort. Breast Cancer Res Treat 145, 535–543 (2014). https://doi.org/10.1007/s10549-014-2934-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-014-2934-6

Keywords

Search

Navigation