Breast Cancer Research and Treatment

, Volume 107, Issue 1, pp 103–111 | Cite as

Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study

  • Agnès Fournier
  • Franco Berrino
  • Françoise Clavel-Chapelon


Large numbers of hormone replacement therapies (HRTs) are available for the treatment of menopausal symptoms. It is still unclear whether some are more deleterious than others regarding breast cancer risk. The goal of this study was to assess and compare the association between different HRTs and breast cancer risk, using data from the French E3N cohort study. Invasive breast cancer cases were identified through biennial self-administered questionnaires completed from 1990 to 2002. During follow-up (mean duration 8.1 postmenopausal years), 2,354 cases of invasive breast cancer occurred among 80,377 postmenopausal women. Compared with HRT never-use, use of estrogen alone was associated with a significant 1.29-fold increased risk (95% confidence interval 1.02–1.65). The association of estrogen–progestagen combinations with breast cancer risk varied significantly according to the type of progestagen: the relative risk was 1.00 (0.83–1.22) for estrogen–progesterone, 1.16 (0.94–1.43) for estrogen–dydrogesterone, and 1.69 (1.50–1.91) for estrogen combined with other progestagens. This latter category involves progestins with different physiologic activities (androgenic, nonandrogenic, antiandrogenic), but their associations with breast cancer risk did not differ significantly from one another. This study found no evidence of an association with risk according to the route of estrogen administration (oral or transdermal/percutaneous). These findings suggest that the choice of the progestagen component in combined HRT is of importance regarding breast cancer risk; it could be preferable to use progesterone or dydrogesterone.


Breast cancer Cohort Dydrogesterone Estrogen Hormone replacement therapy Menopause Progestagens  Progesterone 



The authors are indebted to all participants for providing the data used in the E3N study and to practitioners for providing pathology reports. They are grateful to R. Chaït, M. Fangon, L. Hoang and M. Niravong for their technical assistance; to the E3N group; to Pr Anne Gompel for her useful comments; and to G. Evans and C. Holmes for the linguistic revision of the manuscript.


This work was carried out with the financial support of the “Mutuelle Générale de l’Education Nationale” (MGEN); European Community; French League against Cancer (LNCC); Gustave Roussy Institute (IGR); French Institute of Health and Medical Research (Inserm); 3M Company; and several General Councils of France. A. Fournier was funded by the French Ministry of Research. The funding sources had no involvement in the present work.


Dr Clavel-Chapelon had full access to all of the data in the study and accepts full responsibility for the integrity of the data and the conduct of the study. She controlled the decision to publish.

Study concept and design: Fournier, Clavel-Chapelon.

Acquisition of data: Clavel-Chapelon.

Analysis and interpretation of data: Fournier, Berrino, Clavel-Chapelon.

Drafting of the manuscript: Fournier.

Critical revision of the manuscript for important intellectual content: Fournier, Berrino, Clavel-Chapelon.

Final approval of the version to be published: Fournier, Berrino, Clavel-Chapelon.


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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Agnès Fournier
    • 1
  • Franco Berrino
    • 2
  • Françoise Clavel-Chapelon
    • 1
  1. 1.Institut National de la Santé et de la Recherche Médicale ERI 20Institut Gustave RoussyVillejuifFrance
  2. 2.Department of Preventive and Predictive MedicineIstituto Nazionale Tumori MilanItaly

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