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Use of Different Postmenopausal Hormone Therapies and Risk of Histology- and Hormone Receptor–Defined Invasive Breast Cancer

Agnès Fournier, Alban Fabre, Sylvie Mesrine, Marie-Christine Boutron-Ruault, Franco Berrino, Françoise Clavel-Chapelon

From the Institut National de la Santé et de la Recherche Médicale, Villejuif, France; Institut Gustave Roussy, Villejuif; EA4045, Universite Paris-Sud, Paris, France; and Istituto Nazionale Tumori, Department of Preventive and Predictive Medicine, Milan, Italy

Corresponding author: Françoise Clavel-Chapelon, PhD, Institut National de la Santé et de la Recherche Médicale, ERI 20, EA 4045, Institut Gustave Roussy, 94805 Villejuif Cedex, France; e-mail: clavel{at}igr.fr

Purpose: We previously found that the risk of invasive breast cancer varied according to the progestagen component of combined postmenopausal hormone therapy (CHT): progesterone, dydrogesterone, or other progestagens. We conducted the present study to assess how these CHTs were associated with histology- and hormone receptor-defined breast cancer.

Patients and Methods: We used data from the French E3N cohort study, with 80,391 postmenopausal women followed for a mean duration of 8.1 years; 2,265 histologically confirmed invasive breast cancers were identified through biennial self-administered questionnaires completed from 1990 to 2002. The relative risks (RRs) were estimated using Cox proportional hazards models.

Results: Compared with postmenopausal hormone therapy (HT) never-use, ever-use of estrogen+progesterone was not significantly associated with the risk of any breast cancer subtype, but increasing duration of estrogen+progesterone was associated with increasing risks of lobular (P = .06) and estrogen receptor–positive/progesterone receptor–negative (ER+/PR–; P = .02). Estrogen+dydrogesterone was associated with a significant increase in risk of lobular carcinoma (RR, 1.7; 95% CI, 1.1 to 2.6). Estrogen+other progestagens was associated with significant increases in risk of ductal and lobular carcinomas (RR, 1.6; 95% CI, 1.3 to 1.8; and 2.0; 95% CI, 1.5 to 2.7, respectively), of ER+/PR+ and ER+/PR– carcinomas (RR, 1.8; 95% CI, 1.5 to 2.1; and 2.6; 95% CI, 1.9 to 3.5, respectively), but not of ER–/PR+ or ER–/PR– carcinomas (RR, 1.0; 95% CI, 0.5 to 2.1; and 1.4; 95% CI, 0.9 to 2.0, respectively).

Conclusion: The increase in risk of breast cancer observed with the use of CHTs other than estrogen+progesterone and estrogen+dydrogesterone seems to apply preferentially to ER+ carcinomas, especially those ER+/PR–, and to affect both ductal and lobular carcinomas.

Supported by Mutuelle Générale de l’Education Nationale; European Community; French League against Cancer; Gustave Roussy Institute; French Institute of Health and Medical Research; 3M Company; several General Councils of France; Fondation pour la Recherche Médicale; Cancéropôle Région Ile-de-France; Direction Générale de la Santé; 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.