In short Article

Menopausal hormone therapy and breast cancer


Research findings published in 2019 lend support to the view that the risk of hormone therapy for menopausal symptoms in women might be underestimated. There has been ongoing debate for years about whether there is a relation between invasive breast cancer and the use of hormones. The 2019 research findings provided evidence for associations with almost all types of therapy, including oral and transdermal oestrogens, combinations of oestrogens and progestogens, and tibolone.  A comprehensive meta-analysis of individual patient data of over 100,000 women with breast cancer from 24 prospective observational studies found an association between invasive breast cancer and hormone therapy which was likely to be causative. Calculations show that about 5% of the cases of invasive breast cancer in women might be explained by menopausal hormone therapy. The risk proved highest for oestrogen/progestogen combination therapies. In addition, the invasive breast cancer risk increases with the duration of use, and remains increased for years after cessation of the hormone therapy. It is also important to take into account that there is limited evidence for a clinically relevant effect of hormone therapy on menopausal symptoms, compared to placebo.

  • Doctors should be highly reticent about prescribing hormone therapy for menopausal symptoms.
  • Although the risk of invasive breast cancer is only slightly increased, this is hardly ever justified by the limited effects of hormone treatment.

  1. Collaborative Group on Hormonal Factors in Breast Cancer. Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence. Lancet. 2019;394(10204):1159-1168.
  2. Gezondheidsraad. Hormoontherapie voor vrouwen in de postmenopauze. Achtergronddocument bij het advies Maat houden met medisch handelen. Den Haag 2017. Via: https://www.gezondheidsraad.nl/documenten/adviezen/2017/06/21/maat-houden-met-medisch-handelen.
  3. Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Collaborative Group on Hormonal Factors in Breast Cancer. [published correction appears in Lancet 1997 Nov 15;350(9089):1484] Lancet. 1997;350(9084):1047-1059.
  4. Bouma J, De Jonge M, De Laat EAT, Eekhof H, Engel HF, Groeneveld FPMJ et al. NHG-Standaard De overgang. Huisarts Wet 2012;55(4):168-72. Via: https://www.nhg.org/standaarden/volledig/nhg-standaard-de-overgang.
  5. Maclennan AH, Broadbent JL, Lester S, Moore V. Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flushes. Cochrane Database Syst Rev. 2004(4):Cd002978.
  6. Marjoribanks J, Farquhar C, Roberts H, Lethaby A, Lee J. Long-term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev. 2017;1:Cd004143.
  7. Vandenbroucke JP, Psaty BM. Benefits and risks of drug treatments: how to combine the best evidence on benefits with the best data about adverse effects. JAMA. 2008;300(20):2417-2419.
  8. Bosco JL, Silliman RA, Thwin SS, Geiger AM, Buist DS, Prout MN, et al. A most stubborn bias: no adjustment method fully resolves confounding by Mustacchi P. Ramazzini and Rigoni-Stern on parity and breast cancer. Clinical impression and statistical corroboration indication in observational studies. J Clin Epidemiol. 2010;63(1):64-74.
  9. Mustacchi P. Ramazzini and Rigoni-Stern on parity and breast cancer. Clinical impression and statistical corroboration.  Arch Intern Med. 1961 Oct;108:639-42.
  10. Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, et al. Women’s Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA 2004;291(14):1701–1712.
  11. Manson JE, Chlebowski RT, Stefanick ML, Aragaki AK, Rossouw JE, Prentice RL, et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women’s Health Initiative randomized trials. JAMA 2013;310(13):1353-68.
  12. Vandenbroucke JP. The HRT controversy: observational studies and RCTs fall in line. Lancet 2009;373(9671):1233-5.
  13. National Institute of Clinical Evidence (NICE). Menopause: diagnosis and management. NICE guideline [NG23] 2015. Via: https://www.nice.org.uk/guidance/ng23/resources/menopausediagnosis-and-management-1837330217413.
  14. NVOG-richtlijn Management rondom menopauze. Utrecht 2018. Via: https://www.nvog.nl/wp-content/uploads/2018/06/Inleiding-NVOG-richtlijn-Menopauze-management-def-2018.pdf.
  15. Asi N, Mohammed K, Haydour Q, Gionfriddo MR, Vargas OL, Prokop LJ, et al. Progesterone vs. synthetic progestins and the risk of breast cancer: a systematic review and meta-analysis. Syst Rev. 2016;5(1):121.
  16. Cordina-Duverger E, Truong T, Anger A, Sanchez M, Arveux P, Kerbrat P, et al. Risk of breast cancer by type of menopausal hormone therapy: a case-control study among post-menopausal women in France. PLoS One. 2013;8(11):e78016.
  17. Fournier A, Fabre A, Mesrine S, Boutron-Ruault MC, Berrino F, Clavel-Chapelon F. Use of different postmenopausal hormone therapies and risk of histology- and hormone receptor-defined invasive breast cancer. J Clin Oncol 2008;26(8):1260-1268.

Authors

  • Frans M. Helmerhorst, prof. dr
  • Jan P. Vandenbroucke
  • Hein J.E.M. Janssens, dr, general practitioner