Originally published as JCO Early Release 10.1200/JCO.2008.21.6432 on September 14 2009

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Estrogen-Progestagen Menopausal Hormone Therapy and Breast Cancer: Does Delay From Menopause Onset to Treatment Initiation Influence Risks?

From Institut National de la Santé et de la Recherche Médicale; Université Paris-Sud, Villejuif, France.

Corresponding author: Françoise Clavel-Chapelon, PhD, Institut National de la Santé et de la Recherche Médicale ERI 20, Equipe E3N, Institut Gustave Roussy, 39 rue Camille Desmoulins, F-94805 Villejuif Cedex, France; e-mail: clavel{at}igr.fr.

Purpose To investigate whether the relation between estrogen-progestagen menopausal hormone therapy (EP-MHT) and breast cancer risk varies according to the delay between menopause onset and treatment initiation.

Participants and Methods Between 1992 and 2005, 1,726 invasive breast cancers were identified among 53,310 postmenopausal women from the French E3N cohort (mean duration of follow-up, 8.1 years). Hazard ratios (HRs) and CIs were estimated using Cox models, with MHT never users as the reference.

Results Among recent users of EP-MHT, the risk of breast cancer varied according to the timing of treatment initiation. This variation was confined to short durations of use ( 2 years): the HR was 1.54 (95% CI, 1.28 to 1.86) for short treatments initiated in the 3-year period following menopause onset and 1.00 (95% CI, 0.68 to 1.47) for short treatments initiated later (P = .04 for homogeneity). However, this pattern of risks was not observed in users of EP-MHT containing progesterone, among whom there was no significantly increased risk associated with short duration of use (HR was 0.87 [95% CI, 0.57 to 1.32] for treatments initiated 3 years after menopause, and HR was 0.90 [95% CI, 0.45 to 1.81] for treatments initiated later). Longer durations of EP-MHT use were generally associated with increases in breast cancer risk, whatever the gap time.

Conclusion Our results suggest that, for some EP-MHT, the timing of treatment initiation transiently modulates the risk of breast cancer and that, when initiated close to menopause, even short durations of use are associated with an increased breast cancer risk. Estrogen + progesterone combinations might be an exception in this regard.

See accompanying editorial on page 5116

Supported by Mutuelle Générale de l'Education Nationale, European Community, French League Against Cancer, Gustave Roussy Institute, Institut National de la Santé et de la Recherche Médicale, 3M Company, several General Councils of France, Direction Générale de la Santé, and Agence Française de Sécurité Sanitaire des Produits de Santé.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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