Breast Cancer Research and Treatment

, Volume 145, Issue 2, pp 535–543 | Cite as

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

  • Agnès FournierEmail author
  • Sylvie Mesrine
  • Laure Dossus
  • Marie-Christine Boutron-Ruault
  • Françoise Clavel-Chapelon
  • Nathalie Chabbert-Buffet


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.


Menopausal hormone therapy Cohort study Breast cancer Estrogens Progestagens 



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.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Agnès Fournier
    • 1
    • 2
    • 3
    Email author
  • Sylvie Mesrine
    • 1
    • 2
    • 3
  • Laure Dossus
    • 1
    • 2
    • 3
  • Marie-Christine Boutron-Ruault
    • 1
    • 2
    • 3
  • Françoise Clavel-Chapelon
    • 1
    • 2
    • 3
  • Nathalie Chabbert-Buffet
    • 4
  1. 1.Inserm, Center for Research in Epidemiology and Population Health, U1018, Nutrition, Hormones and Women’s Health TeamVillejuifFrance
  2. 2.Univ Paris-SudVillejuifFrance
  3. 3.Institut Gustave RoussyVillejuifFrance
  4. 4.Department of Obstetrics-Gynecology and Reproductive Medicine, APHP Hôpital TenonUniv. Pierre Et Marie Curie Paris 06ParisFrance

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