Menopausal hormone therapy and breast cancer risk: Impact of different treatments. The European Prospective Investigation into Cancer and Nutrition

Kjersti Bakken, Agnès Fournier, Eiliv Lund, Marit Waaseth, Vanessa Dumeaux, Franoise Clavel-Chapelon, Alban Fabre, Bertrand Hémon, Sabina Rinaldi, Véronique Chajes, Nadia Slimani, Naomi E. Allen, Gillian K. Reeves, Sheila Bingham, Kay Tee Khaw, Anja Olsen, Anne Tjønneland, Laudina Rodriguez, Maria José SÁnchez, Pilar Amiano EtxezarretaEva Ardanaz, Maria José Tormo, Petra H. Peeters, Carla H. Van Gils, Annika Steffen, Mandy Schulz, Jenny Chang-Claude, Rudolf Kaaks, Rosario Tumino, Valentina Gallo, Teresa Norat, Elio Riboli, Salvatore Panico, Giovanna Masala, Carlos A. GonzÁlez, Franco Berrino

Research output: Contribution to journalArticlepeer-review


Menopausal hormone therapy (MHT) is characterized by use of different constituents, regimens and routes of administration. We investigated the association between the use of different types of MHT and breast cancer risk in the EPIC cohort study. The analysis is based on data from 133,744 postmenopausal women. Approximately 133,744 postmenopausal women contributed to this analysis. Information on MHT was derived from country-specific self-administered questionnaires with a single baseline assessment. Incident breast cancers were identified through population cancer registries or by active follow-up (mean: 8.6 yr). Overall relative risks (RR) and 95% confidence interval (CI) were derived from country-specific Cox proportional hazard models estimates. A total of 4312 primary breast cancers were diagnosed during 1,153,747 person-years of follow-up. Compared with MHT never users, breast cancer risk was higher among current users of estrogen only (RR: 1.42, 95% CI 1.23 1.64) and higher still among current users of combined MHT (RR: 1.77, 95% CI 1.40 2.24; p = 0.02 for combined vs. estrogen-only). Continuous combined regimens conferred a 43% (95% CI: 19 72%) greater risk compared with sequential regimens. There was no significant difference between progesterone and testosterone derivatives in sequential regimens. There was no significant variation in risk linked to the estrogenic component of MHT, neither for oral vs. cutaneous administration nor for estradiol compounds vs. conjugated equine estrogens. Estrogen-only and combined MHT uses were associated with increased breast cancer risk. Continuous combined preparations were associated with the highest risk. Further studies are needed to disentangle the effects of the regimen and the progestin component.

Original languageEnglish
Pages (from-to)144-156
Number of pages13
JournalInternational Journal of Cancer
Issue number1
Publication statusPublished - Jan 1 2011


  • Breast cancer
  • Cohort studies
  • Dosage
  • Epidemiology
  • Estrogens
  • HRT
  • Menopause
  • Progestins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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