Skip to main content

Advertisement

SpringerLink
Log in

How to Prescribe MHT According to the Risk of Breast Cancer

  • Management of Menopause (K-E Huang, Section Editor)
  • Published:
Current Obstetrics and Gynecology Reports Aims and scope Submit manuscript

Abstract

Breast cancer is the primary cancer in women in most countries in the world. It is a constant fear to increase the risk in the context of any hormonal treatment prescribed by physicians and used by women. Despite the fact that breast cancer is in most cases a hormone-dependent cancer, the possible increase in risk related to menopause hormonal treatment (MHT) is not as great, is associated with duration, is less important with estrogen treatment alone than combined estrogen/progestin treatment, can be limited by certain preparations, and in a majority of studies, is not associated with increases in mortality, and in some cases, a decrease in mortality is seen. Nevertheless, it is important to select patients according their own risk of breast cancer before making the decision for any hormonal administration and evaluate the benefit/risk ratio. Breast cancer is multifactorial and combines genetic and environmental factors. Some scores exist and help to evaluate the range of the life risk for a given woman even though they are not very precise in predicting the risk. If a genetic cause cannot be modified, some lifestyle modifications could help to decrease the relative risk of breast cancer. We will review the evidence concerning the risk factors for breast cancer, the management of women with moderate to high risk, and discuss the role of a chemical prevention in these patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance; a comprehensive paper on management of women at risk for breast cancer •• Of major importance

  1. Armstrong AC, Evans GD. Management of women at high risk of breast cancer. BMJ. 2014;348:g2756. This review defines who is at high risk of breast cancer and outlines the management options.

  2. Santen RJ, Yue W, Heitjan DF. Occult breast tumor reservoir: biological properties and clinical significance. Horm Cancer. 2013;4:195–207. Mathematical models were applied to interpret the promoter effects of MHTon pre-existing, occult lesions and minimally initiated de novo tumors.

  3. Moolgavkar SH. Hormones and multistage carcinogenesis. Cancer Surv. 1986;5:635–48. This paper has calculated the lag time for breast cacner for the first time and howed the necessity of several sequential events to progress from a normal state to cancer.

    CAS  PubMed  Google Scholar 

  4. Santen RJ, Yue W, Heitjan DF. Modeling of the growth kinetics of occult breast tumors: role in interpretation of studies of prevention and menopausal hormone therapy. Cancer Epidemiol Biomarkers Prev. 2012;21:1038–48. This paper shows the development of the mathematical models used for Santen et al. [2].

  5. Boyd NF, Martin LJ, Yaffe MJ, Minkin S. Mammographic density and breast cancer risk: current understanding and future prospects. Breast Cancer Res 2011;13:223. A review on the contribution of this group on the role of breast density as a risk factor for breast cancer.

  6. Hou N, Hong S, Wang W, et al. Hormone replacement therapy and breast cancer: heterogeneous risks by race, weight, and breast density. J Natl Cancer Inst. 2013;105:1365–72. Interaction between BMI, breast density and risk of breast cancer on a large cohort of screened women.

  7. Murphy RA, Schairer C, Gierach GL, et al. Beyond breast cancer: mammographic features and mortality risk in a population of healthy women. PLoS One. 2013;8:e78722.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Clavel-Chapelon F, Group ENE. Differential effects of reproductive factors on the risk of pre- and postmenopausal breast cancer. Results from a large cohort of French women. Br J Cancer. 2002;86:723–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Petracci E, Decarli A, Schairer C et al. Risk factor modification and projections of absolute breast cancer risk. J Natl Cancer Inst 2011;103:1037–48.

  10. Powell M, Jamshidian F, Cheyne K, et al. Assessing breast cancer risk models in Marin County, a population with high rates of delayed childbirth. Clin Breast Cancer. 2014;14:212–220 e211.

    Article  PubMed  Google Scholar 

  11. Manson JE, Chlebowski RT, Stefanick ML, 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;310:1353–68. An update on the riks benefits in the RCT WHIand during the folling period.

    Article  CAS  PubMed  Google Scholar 

  12. Gompel A, Santen RJ. Hormone therapy and breast cancer risk 10 years after the WHI. Climacteric. 2012;15:241–9. Meaningful review on HRT and breast cancer risk in 2012.

    Article  CAS  PubMed  Google Scholar 

  13. Cuzick J, Sestak I, Bonanni B, et al. Selective oestrogen receptor modulators in prevention of breast cancer: an updated meta-analysis of individual participant data. Lancet. 2013;381:1827–34. A complete metanalysis on prevention trials.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Anderson GL, Chlebowski RT, Rossouw JE, et al. Prior hormone therapy and breast cancer risk in the Women’s Health Initiative randomized trial of estrogen plus progestin. Maturitas. 2006;55:103–15. In this papzer the WHI autnros developped the previous sue of MHT and risk of breast cancer.

  15. Fournier A, Berrino F, Clavel-Chapelon F. Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. Breast Cancer Res Treat. 2008;107:103–11. The E3N study and its demonstration on the lower risk of breast cancer with progesterone and dydrogesterone.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Cordina-Duverger E, Truong T, Anger A, 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:e78016.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Lyytinen H, Pukkala E, Ylikorkala O. Breast cancer risk in postmenopausal women using estradiol–progestogen therapy. Obst Gynecol. 2009;113:65–73.

    Article  Google Scholar 

  18. Fournier A, Mesrine S, Dossus L, et al. Risk of breast cancer after stopping menopausal hormone therapy in the E3N cohort. Breast Cancer Res Treat. 2014;145:535–43.

    Article  CAS  PubMed  Google Scholar 

  19. Bakken K, Fournier A, Lund E et al. Menopausal hormone therapy and breast cancer risk: impact of different treatments. The European Prospective Investigation into Cancer and Nutrition. Int J Cancer 2011;128:144–56.

  20. Kenemans P, Bundred NJ, Foidart JM, et al. Safety and efficacy of tibolone in breast-cancer patients with vasomotor symptoms: a double-blind, randomised, non-inferiority trial. Lancet Oncol. 2009;10:135–46.

    Article  CAS  PubMed  Google Scholar 

  21. 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. Lancet. 1997;350:1047–59. A potent pool analysis of the previosu studies on HRt and breast cancer.

    Article  Google Scholar 

  22. Prentice RL, Chlebowski RT, Stefanick ML, et al. Estrogen plus progestin therapy and breast cancer in recently postmenopausal women. Am J Epidemiol. 2008;167:1207–16. Introducing the concept of decrease risk with treatment started after few years following menopause.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Fournier A, Mesrine S, Boutron-Ruault MC, Clavel-Chapelon F. Estrogen-progestagen menopausal hormone therapy and breast cancer: does delay from menopause onset to treatment initiation influence risks? J Clin Oncol. 2009;27:5138–43.

    Article  PubMed  Google Scholar 

  24. Kerlikowske KCA, Buist DS, Cummings SR, Vachon C, Vacek P, Miglioretti DL. Breast cancer risk by breast density, menopause, and postmenopausal hormone therapy use. J Clin Oncol. 2010;28:3830–7. The first paper to show no increased risk of breast cancer in HRT in women with low breast density.

    Article  PubMed Central  PubMed  Google Scholar 

  25. Hamajima N, Hirose K, Tajima K, et al. Alcohol, tobacco and breast cancer–collaborative reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without the disease. Br J Cancer. 2002;87:1234–45.

    Article  CAS  PubMed  Google Scholar 

  26. Al-Sader H, Abdul-Jabar H, Allawi Z, Haba Y. Alcohol and breast cancer: the mechanisms explained. J Clin Med Res. 2009;1:125–31.

    CAS  PubMed Central  PubMed  Google Scholar 

  27. Giannakeas V, Lubinski J, Gronwald J, et al. Mammography screening and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers: a prospective study. Breast Cancer Res Treat. 2014;147:113–8.

    Article  CAS  PubMed  Google Scholar 

  28. Plu-Bureau GTJ, Sitruk-Ware R, Asselain B, Mauvais-Jarvis P. Cyclical mastalgia as a marker of breast cancer susceptibility: results of a case-control study among French women. Br J Cancer. 1992;65:945–9. First paper to demosntrated the association of chronic cyclic mastalgia and breast cancer risk increase in a French population.

  29. Goodwin PJ, DeBoer G, Clark RM, et al. Cyclical mastopathy and premenopausal breast cancer risk. Results of a case-control study. Breast Cancer Res Treat. 1995;33:63–73. Paper showing the association between mastalgia and breast cancer risk in a Canadian population.

  30. Crandall CJ, Aragaki AK, Cauley JA, et al. Breast tenderness and breast cancer risk in the estrogen plus progestin and estrogen-alone women’s health initiative clinical trials. Breast Cancer Res Treat. 2012;132:275–85. In the WHI combined MHT treatment trial , mastalgia preexisting or occurring under MHT is associated with an increased risk of breast cancer.

  31. Crandall CJ, Aragaki AK, Cauley JA, et al. Breast tenderness after initiation of conjugated equine estrogens and mammographic density change. Breast Cancer Res Treat. 2012;131:969–79.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Soderqvist G, von Schoultz B. Lessons to be learned from clinical studies on hormones and the breast. Maturitas. 2004;49:90–6.

    Article  PubMed  Google Scholar 

  33. Nelson HD, Smith ME, Griffin JC, Fu R. Use of medications to reduce risk for primary breast cancer: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2013;158:604–14.

    Article  PubMed  Google Scholar 

  34. DeCensi A, Bonanni B, Maisonneuve P, et al. A phase-III prevention trial of low-dose tamoxifen in postmenopausal hormone replacement therapy users: the HOT study. Ann Oncol. 2013;24:2753–60.

    Article  CAS  PubMed  Google Scholar 

  35. Harvey JA, Pinkerton JV, Baracat EC, et al. Breast density changes in a randomized controlled trial evaluating bazedoxifene/conjugated estrogens. Menopause. 2013;20:138–45.

    PubMed  Google Scholar 

  36. Pinkerton JV, Harvey JA, Pan K, et al. Breast effects of bazedoxifene-conjugated estrogens: a randomized controlled trial. Obstet Gynecol. 2013;121:959–68.

    Article  CAS  PubMed  Google Scholar 

  37. Mauvais-Javis P, Baudot N, Castaigne D, et al. trans-4-Hydroxytamoxifen concentration and metabolism after local percutaneous administration to human breast. Cancer Res. 1986;46:1521–5. Pharmacokinetics, breast tissue and systemic distribution of percutaneous adminsitration of 4 hydroxy tamoxifen, a forgotten concept.

Download references

Compliance with Ethics Guidelines

Conflict of Interest

Professor Anne Gompel is a past board member of IMS.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

  1. Unité de Gyéncologie Endocrinienne, Université Paris Descartes, Hopitaux Universitaires Paris Centre, Port Royal-Cochin, 53 avenue de l’Observatoire, Paris, 75014, France

    Anne Gompel

Authors
  1. Anne Gompel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anne Gompel.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gompel, A. How to Prescribe MHT According to the Risk of Breast Cancer. Curr Obstet Gynecol Rep 3, 238–245 (2014). https://doi.org/10.1007/s13669-014-0100-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13669-014-0100-0

Keywords

Search

Navigation