Hormone replacement therapy use and variations in the risk of breast cancer

Authors

  • L Opatrny,

    1. Division of Internal Medicine, Department of Medicine, McGill University Health Center
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  • S Dell’Aniello,

    1. McGill Pharmacoepidemiology Research Unit, Department of Epidemiology and Biostatistics
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  • S Assouline,

    1. Division of Hematology-Oncology, Department of Medicine, SMBD Jewish General Hospital, McGill University, Montreal, Quebec, Canada
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  • S Suissa

    Corresponding author
    1. McGill Pharmacoepidemiology Research Unit, Department of Epidemiology and Biostatistics
      Dr S Suissa, Division of Clinical Epidemiology, Royal Victoria Hospital, 687 Pine avenue west, Ross 4.29, Montreal, Québec, Canada H3A 1A1. Email samy.suissa@clinepi.mcgill.ca
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Dr S Suissa, Division of Clinical Epidemiology, Royal Victoria Hospital, 687 Pine avenue west, Ross 4.29, Montreal, Québec, Canada H3A 1A1. Email samy.suissa@clinepi.mcgill.ca

Abstract

Objective  To determine the effect of different types and formulations of hormone replacement therapy (HRT) on the risk of breast cancer in postmenopausal women.

Design  Population-based case–control study.

Setting  UK, 1988–2004.

Participants  Women 50–75 years between 1998 and 2004.

Main outcome measures  Breast cancer incidence to estimate the rate ratio (RR) associated with use of various HRTs over a 30-year period.

Results  We identified 6347 incident cases of breast cancer that were matched with 31 516 controls. Cases were on average 61 years at diagnosis and 22% had undergone a hysterectomy. The rate of breast cancer was increased with the use of opposed estrogens in oral form (adjusted RR 1.38; 95% CI 1.27–1.49) in contrast to patch form (RR 1.08; 95% CI 0.81–1.43). This rate was similarly elevated with both continuous (RR 1.29; 95% CI 1.07–1.56) and sequential (RR 1.33; 95% CI 1.21–1.46) forms of opposed estrogen. The rate of breast cancer was not increased among exclusive users of unopposed estrogens (RR 0.97; 95% CI 0.86–1.09) or of tibolone (RR 0.86; 95% CI 0.65–1.13). Users of tibolone who had switched from opposed estrogens, however, had an elevated rate (RR 1.29; 95% CI 1.09–1.52). The rate of breast cancer increased by 25% (95% CI 20–30%) with every ten prescriptions of orally administered opposed estrogen.

Conclusions  The risk of breast cancer varies with the formulation and preparation of HRT. Opposed estrogens (progesterone–estrogen) in oral form are associated with an increased risk of breast cancer, which increases with use. Transdermal opposed estrogens, unopposed estrogens and tibolone do not increase this risk. However, this study is an observational study that carries risks of various biases, and thus the findings need to be interpreted with caution.

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