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Date of release: 29 June, 2009

Short-term suspension of hormone therapy and mammography recall


In a paper recently published in Annals of Internal Medicine, Buist and colleagues [1] reported the results of a randomized, controlled trial to test whether 1 or 2 months’ suspension of hormone replacement therapy (HRT) before screening mammography would decrease additional mammographic imaging recalls in women aged 45–80 years.


A total of 1704 women aged 45–80 years who used HRT at their most recent index mammography and who were due for a screening mammography and still using hormone therapy were recruited. Block random assignment was carried out by breast density and hormone therapy type to no suspension of hormone therapy or to suspension for 1 or 2 months before mammography. One blinded expert radiologist interpreted all mammograms. The primary endpoint was mammography recall and the secondary endpoint was change in mammographic breast density (percentage and dense area) between the index and study mammograms.


The rate of mammography recall was 11.3% in the no-suspension group, 12.3% in the 1-month suspension group and 9.8% in the 2-month suspension group. No subgroups were identified in which brief suspension of hormone therapy resulted in decreased mammography recall. With suspension of HRT, decreases in the percentage of breast density were orderly and statistically significant: 0.1% for the no-suspension group, -0.9% for the 1-month suspension group and -1.5% for the 2-month suspension group. Similar ordered decreases were observed for dense area. Return of menopausal symptoms was increased in those women who had suspended HRT. Interestingly, 61% of women approached for recruitment into this trial declined because they were concerned about recurrence of menopausal symptoms.


The authors concluded that brief hormone therapy suspension was associated with small changes in breast density but did not affect recall rates and that short-term suspension of HRT before mammography was not justified.

Comment

Mammography remains the first-choice screening method proven to reduce breast cancer mortality but it is imperfect. Approximately 10% of women screened for breast cancer receive a recall notice and, of these, only 4–5% will receive a diagnosis of breast cancer within 1 year. The consequences of this high recall rate include distress to the women recalled plus a significant impact on health-care costs.
It is well known that, as breast density increases, the sensitivity and specificity of mammography decrease. Higher breast density is also a significant risk factor for breast cancer. However, breast density is not static. Density increases between the follicular and luteal phases of the menstrual cycle and decreases after the menopause.
HRT increases mammographic density, with combined estrogen and progestin therapy causing a greater increase in density than estrogen alone or tibolone in a dose-related manner. It has been suggested that the use of HRT may reduce the benefit of screening mammography and increase the rate of recall. In 2003, Chlebowski and colleagues [2] reported the effect of combined estrogen + progestin therapy on breast cancer risk and mammographic screening in the Women’s Health Initiative (WHI) trial. An increase in abnormal mammography was seen after 1 year in HRT users compared to non-users (31.5% vs. 21.2% overall). There have been a number of papers published before and after the WHI study showing a reduction in mammographic density with short-term cessation of HRT prior to screening mammography [3–5]. Such advice was also conveyed by professional medical associations.
However, in 2008, Weaver and colleagues [6] published results from a clinical trial of 48 women who had mammography performed whilst on HRT and then after a period of 4 weeks withdrawal from HRT. No significant changes in mammographic density were observed by either visual or computer methods. There were no changes in breast pain or tenderness during mammography either before or after the month’s cessation and radiographic measurements were not significantly altered by the 4-week cessation of HRT.
No large-scale, randomized trials have measured how quickly breast density changes with hormone therapy suspension nor, importantly, have any studies quantified the amount of density reduction needed to improve mammography performance.
The recent paper from Buist and colleagues clearly shows that, although short-term cessation of HRT results in a small decrease in mammographic density, such cessation led to a significant recurrence of menopausal symptoms and had no effect on reducing the rate of mammography recall [1].
In summary, this trial shows that short-term cessation of hormone therapy prior to mammography does not improve the rate of mammography recall and that women are reluctant to agree to such an intervention. Rather than needlessly cease HRT, clinicians should seek to prescribe HRT in a regimen and dose which minimize the impact on the breast in general and mammographic density in particular wherever possible.

Comentario

Rodney J. Baber
Associate Professor of Obstetrics and Gynaecology at The University of Sydney, Head, Menopause Unit, The Royal North Shore Hospital of Sydney, New South Wales, Australia

    References

  1. Buist D, Anderson ML, Reed SD, et al. Short-term hormone therapy suspension and mammography recall: a randomized trial. Ann Intern Med 2009;150:752-65. Published June 2, 2009.
    http://www.ncbi.nlm.nih.gov/pubmed/19487710

  2. Chlebowski RT, Hendrix SL, Langer RD, et al. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Womens Health Initiative randomized trial. JAMA 2003;289:3243-53.
    http://www.ncbi.nlm.nih.gov/pubmed/12824205

  3. Harvey JA, Pinkerton JV, Herman CR. Short-term cessation of hormone replacement therapy and improvement of mammographic specificity. J Natl Cancer Inst 1997;89:1623-5.
    http://www.ncbi.nlm.nih.gov/pubmed/9362162

  4. Speroff L. The impact of the Womens Health Initiative on clinical practice. J Soc Gynecol Invest 2002;9:251-3.
    http://www.ncbi.nlm.nih.gov/pubmed/12383908

  5. Burnside ES, Trentham-Dietz A, Kelcz F, Collins J. An example of breast cancer regression on imaging. Radiol Case Rep 2006;1:27-37.
    http://radiology.casereports.net/index.php/rcr/article/viewArticle/4/183

  6. Weaver K, Kataoka M, Murray J, et al. Does a short cessation of HRT decrease mammographic density? Maturitas 2008;59:315-22.
    http://www.ncbi.nlm.nih.gov/pubmed/18448281