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Date of release: 08 August, 2016

Breast cancer incidence and changes in use of menopausal hormone therapy in European countries

Since the first publication of results from the randomized controlled trial by the Women’s Health Initiative (WHI) [1], consumption of menopausal hormone therapy (MHT) has decreased in most countries [2]. Several studies have reported a coincidental decrease in incidence of breast cancer (BC), but the extent of this decrease and the length of time between the drop in MHT use and the change in BC incidence have varied between countries [3]. This may reflect differences between studies, in BC incidence, in MHT use (prevalence of use and regimens used), in confounding factors (i.e. BC screening), but also in study methodology.

We recently published the results of a study, 'Menopausal hormone therapy use in relation to BC incidence in 11 European countries', whose aim was to analyze the changes in BC incidence and MHT use, using the same methodology [4]. BC incidence data were provided from cancer registries, and MHT sales data were extracted from health sales databases for the years 2003 to 2013.

The changes in BC incidence varied widely between the countries. There was an increase in some countries, a decrease in others and no change in the remainder. Conversely, for MHT sales, the drop was consistent in all countries for the whole period of follow-up, varying between 42.1% and 76%. We found no statistical evidence of an association between BC incidence and MHT sales in the past year (p = 0.60).

Comment

Contrary to others, we found no evidence of a relation between BC incidence and MHT sales. MHT sales data were uniformly estimated and BC incidence data were provided only by national cancer registries, while in many published articles BC incidence and MHT prevalence were taken from various sources and approximations were often inevitable when analyzing them [3]. Nevertheless, similarly to most published studies, the present study is also an ecological study, with several limitations: these studies use aggregate data to explore correlations and time trends, but individual data are not available and so no inferences can be made about cause and effect [5].

The reported incidence of BC is clearly influenced by BC screening programs [6]. The increase in BC incidence observed in some countries may, at least partially, be attributed to the implementation of screening.

Confounding factors such as reproductive factors and environmental factors (i.e. obesity, alcohol intake, smoking status, physical activity, medication use) may have a more profound impact on BC incidence in some countries than in others and may change with time [7]. Furthermore, BC incidence varies considerably between countries and is perhaps influenced by ethnic variability and genetic predisposition [8]. Recent studies have found interactions between genetic predisposition and MHT use [9].

The differences observed between our results and those of other studies may also be explained by the variability in the length of follow-up. Most publications have covered a study period of more than 10 years, but stopped soon after the publication of the results of the WHI trial (they stopped in 2005–2006) [3]. In our study, we observed that BC incidence tended to stabilize or increase after 2005, in most countries, while MHT sales decreased even further. A recent study in New Zealand with a follow-up period of 8 years after the WHI did not find any association between changes in MHT use and the incidence rate of BC [10].

The relationship between MHT and BC remains complex and still needs to be clarified, although numerous data suggest an increased risk of BC or BC recurrence in women using MHT [1, 11, 12].

Caroline Antoine and Serge Rozenberg


OBGYN Department, Menopause Clinic, CHU Saint-Pierre (ULB/VUB), Brussels, Belgium



    References

  1. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA 2002;288:321-33


    http://www.ncbi.nlm.nih.gov/pubmed/12117397

  2. Ameye L, Antoine C, Paesmans M, de Azambuja E, Rozenberg S. Menopausal hormone therapy use in 17 European countries during the last decade. Maturitas 2014;79:287-91


    http://www.ncbi.nlm.nih.gov/pubmed/25156453

  3. Antoine C, Ameye L, Paesmans M, Rozenberg S. Systematic review about breast cancer incidence in relation to hormone replacement therapy use. Climacteric 2014;17:116-32


    http://www.ncbi.nlm.nih.gov/pubmed/23909434

  4. Antoine C, Ameye L, Paesmans M, de Azambuja E, Rozenberg S. Menopausal hormone therapy use in relation to breast cancer incidence in 11 European countries. Maturitas 2016;84:81-8


    http://www.ncbi.nlm.nih.gov/pubmed/26654400

  5. Michels KB. The rise and fall of breast cancer rates. BMJ 2012;344:d8003


    http://www.ncbi.nlm.nih.gov/pubmed/22290098

  6. Zahl PH, Strand BH, Maehlen J. Incidence of breast cancer in Norway and Sweden during introduction of nationwide screening: prospective cohort study. BMJ 2004;328:921-4


    http://www.ncbi.nlm.nih.gov/pubmed/15013948

  7. Gompel A, Plu-Bureau G. Is the decrease in breast cancer incidence related to a decrease in postmenopausal hormone therapy? Ann N Y Acad Sci 2010;1205:268-76


    http://www.ncbi.nlm.nih.gov/pubmed/20840283

  8. Eurostat report.


    http://info.cancerresearchuk.org/cancerstats/types/breast/incidence/

  9. Prentice RL, Huang Y, Hinds DA, et al. Variation in the FGFR2 gene and the effects of postmenopausal hormone therapy on invasive breast cancer. Cancer Epidemiol Biomarkers Prev 2009;18:3079-85


    http://www.ncbi.nlm.nih.gov/pubmed/19861516

  10. Farmer R, Fenton A. Time trends in breast cancer and menopause hormone therapy use in New Zealand. Climacteric 2016;19:42-8


    http://www.ncbi.nlm.nih.gov/pubmed/26574628

  11. 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


    http://www.ncbi.nlm.nih.gov/pubmed/19752341

  12. Kenemans P, Bundred NJ, Foidart JM, et al.; LIBERATE Study Group. 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


    http://www.ncbi.nlm.nih.gov/pubmed/19167925