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Menopausal hormone therapy and breast cancer: what is the true size of the increased risk?

Abstract

BACKGROUND

Menopausal hormone therapy (MHT) increases breast cancer risk; however, most cohort studies omit MHT use after enrolment and many infer menopausal age.

METHODS

We used information from serial questionnaires from the UK Generations Study cohort to estimate hazard ratios (HRs) for breast cancer among post-menopausal women with known menopausal age, and examined biases induced when not updating data on MHT use and including women with inferred menopausal age.

RESULTS

Among women recruited in 2003-2009, at 6 years of follow-up, 58 148 had reached menopause and 96% had completed a follow-up questionnaire. Among 39 183 women with known menopausal age, 775 developed breast cancer, and the HR in relation to current oestrogen plus progestogen MHT use (based on 52 current oestrogen plus progestogen MHT users in breast cancer cases) relative to those with no previous MHT use was 2.74 (95% confidence interval (CI): 2.05-3.65) for a median duration of 5.4 years of current use, reaching 3.27 (95% CI: 1.53-6.99) at 15+ years of use. The excess HR was underestimated by 53% if oestrogen plus progestogen MHT use was not updated after recruitment, 13% if women with uncertain menopausal age were included, and 59% if both applied. The HR for oestrogen-only MHT was not increased (HR=1.00; 95% CI: 0.66-1.54).

CONCLUSIONS

Lack of updating MHT status through follow-up and inclusion of women with inferred menopausal age is likely to result in substantial underestimation of the excess relative risks for oestrogen plus progestogen MHT use in studies with long follow-up, limited updating of exposures, and changing or short durations of use.

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  • Authors+Show Affiliations

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    Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK.

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    Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK.

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    Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK.

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    Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK.

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    Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK.

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    Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK.

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    Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK.

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    The National Cancer Registration Service-Eastern Office, Public Health England, Cambridge CB21 5XA, UK.

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    Division of Breast Cancer Research, The Institute of Cancer Research, London SW7 3RP, UK. Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research, London SW7 3RP, UK. Division of Molecular Pathology, The Institute of Cancer Research, London SW7 3RP, UK.

    Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK. Division of Breast Cancer Research, The Institute of Cancer Research, London SW7 3RP, UK.

    Source

    British journal of cancer 115:5 2016 08 23 pg 607-15

    MeSH

    Breast Neoplasms
    Cohort Studies
    Estrogen Replacement Therapy
    Female
    Humans
    Middle Aged

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    27467055

    Citation

    Jones, Michael E., et al. "Menopausal Hormone Therapy and Breast Cancer: what Is the True Size of the Increased Risk?" British Journal of Cancer, vol. 115, no. 5, 2016, pp. 607-15.
    Jones ME, Schoemaker MJ, Wright L, et al. Menopausal hormone therapy and breast cancer: what is the true size of the increased risk? Br J Cancer. 2016;115(5):607-15.
    Jones, M. E., Schoemaker, M. J., Wright, L., McFadden, E., Griffin, J., Thomas, D., ... Swerdlow, A. J. (2016). Menopausal hormone therapy and breast cancer: what is the true size of the increased risk? British Journal of Cancer, 115(5), pp. 607-15. doi:10.1038/bjc.2016.231.
    Jones ME, et al. Menopausal Hormone Therapy and Breast Cancer: what Is the True Size of the Increased Risk. Br J Cancer. 2016 08 23;115(5):607-15. PubMed PMID: 27467055.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Menopausal hormone therapy and breast cancer: what is the true size of the increased risk? AU - Jones,Michael E, AU - Schoemaker,Minouk J, AU - Wright,Lauren, AU - McFadden,Emily, AU - Griffin,James, AU - Thomas,Dawn, AU - Hemming,Jane, AU - Wright,Karen, AU - Ashworth,Alan, AU - Swerdlow,Anthony J, Y1 - 2016/07/28/ PY - 2016/04/06/received PY - 2016/06/30/revised PY - 2016/07/06/accepted PY - 2016/7/29/entrez PY - 2016/7/29/pubmed PY - 2017/5/16/medline SP - 607 EP - 15 JF - British journal of cancer JO - Br. J. Cancer VL - 115 IS - 5 N2 - BACKGROUND: Menopausal hormone therapy (MHT) increases breast cancer risk; however, most cohort studies omit MHT use after enrolment and many infer menopausal age. METHODS: We used information from serial questionnaires from the UK Generations Study cohort to estimate hazard ratios (HRs) for breast cancer among post-menopausal women with known menopausal age, and examined biases induced when not updating data on MHT use and including women with inferred menopausal age. RESULTS: Among women recruited in 2003-2009, at 6 years of follow-up, 58 148 had reached menopause and 96% had completed a follow-up questionnaire. Among 39 183 women with known menopausal age, 775 developed breast cancer, and the HR in relation to current oestrogen plus progestogen MHT use (based on 52 current oestrogen plus progestogen MHT users in breast cancer cases) relative to those with no previous MHT use was 2.74 (95% confidence interval (CI): 2.05-3.65) for a median duration of 5.4 years of current use, reaching 3.27 (95% CI: 1.53-6.99) at 15+ years of use. The excess HR was underestimated by 53% if oestrogen plus progestogen MHT use was not updated after recruitment, 13% if women with uncertain menopausal age were included, and 59% if both applied. The HR for oestrogen-only MHT was not increased (HR=1.00; 95% CI: 0.66-1.54). CONCLUSIONS: Lack of updating MHT status through follow-up and inclusion of women with inferred menopausal age is likely to result in substantial underestimation of the excess relative risks for oestrogen plus progestogen MHT use in studies with long follow-up, limited updating of exposures, and changing or short durations of use. SN - 1532-1827 UR - https://www.unboundmedicine.com/medline/citation/27467055/full_citation L2 - http://dx.doi.org/10.1038/bjc.2016.231 DB - PRIME DP - Unbound Medicine ER -