Correspondence

Hormone Replacement and the Risk of Breast Cancer in Turner's Syndrome

N Engl J Med 2006; 355:2599-2600December 14, 2006

Article

To the Editor:

Turner's syndrome is characterized by estrogen deficiency due to nonfunctioning bilateral streaks of fibrous stroma.1 The benefit of hormone-replacement therapy in patients with this disorder has been well demonstrated. An increased risk of breast cancer in healthy postmenopausal women who receive more than 5 years of hormone-replacement therapy has been reported,2 but data from studies in patients with Turner's syndrome are scarce. However, concern about such patients, which has been raised by an extrapolation of findings from studies involving postmenopausal women, appears to be unwarranted.3

We report on 62 patients with Turner's syndrome and 3 patients with gonadoblastomas who were treated with estrogen–progesterone for decades. Turner's syndrome was diagnosed and karyotyping (Table 1Table 1Karyotypes of 65 Patients with Turner's Syndrome.) was performed as described previously.1,4 The patients began receiving low-dose oral estrogen between the ages of 11 and 19 years, followed by cyclic estrogen–progesterone. Treatment resulted in the onset of menstrual bleeding and full breast development in all patients. During the 10 years before our study began, the patients had received various synthetic and natural estrogens and progesterones, either orally or transdermally. All the patients had received hormone-replacement therapy for more than 25 years and some for more than 30 years (average, 28.6 years), including four patients who had received treatment for 40 to 43 years. After receiving hormone-replacement therapy for more than 25 years, nine menopausal patients received estrogen–progesterone for another 5 to 10 years. All patients underwent mammography from the age of 35 or 40 years and then every 1 or 2 years thereafter; none of them were found to have breast cancer or any benign breast disorder, and none had an increase in the density of breast tissue.

Our report involves continuous hormone-replacement therapy for two to four decades in patients with Turner's syndrome. One limitation of our study is that the doses of the various types of estrogen–progesterone preparations and the administration schedules changed during decades of hormone-replacement therapy; however, this fact does not seem to influence our conclusion. We report on a small number of patients, but Turner's syndrome is rare, and prospective follow-up for decades would be difficult. Among women in our region, there is an 11% incidence of breast cancer. Among postmenopausal women receiving hormone-replacement therapy for more than 5 years, the risk of breast cancer doubles; among those receiving such therapy for 10 to 15 years, the risk more than doubles. Given these statistics, one might expect some breast cancers to develop among the 65 women we studied, but this was not the case.

In conclusion, on the basis of our findings, long-term hormone-replacement therapy does not increase the risk of breast cancer in women with Turner's syndrome. Additional factors, perhaps including ovarian cofactors, may be involved in the apparent increase in the risk of breast cancer associated with hormone-replacement therapy in women without Turner's syndrome.

Peter Bösze, M.D.
Saint Stephen Hospital, 1096 Budapest, Hungary
bosze@t-online.hu

András Tóth, Ph.D.
Miklós Török, M.D.
National Health Center, 1311 Budapest, Hungary

4 References

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   Bosze P, Laszlo J. The streak gonad syndrome. Obstet Gynecol 1979;54:544-548
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   Rossouw JE, Anderson GL, Prentice RL, et al. Risk and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA 2002;288:321-333
   CrossRef | Web of Science | Medline

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   Warren MP, Chua A. Appropriate use of estrogen replacement therapy in adolescents and young adults with Turner syndrome and hypopituitarism in light of the Women's Health Initiative. Growth Horm IGF Res 2006;16:Suppl A:S98-S102
   CrossRef | Web of Science | Medline

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   Gaal M, Toth A, Bosze P, Laszlo J. 46,X,i(Xq)/45,X mosaicism with gonadal dysgenesis associated with 21p-. Clin Genet 1984;25:79-83
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Citing Articles (4)

Citing Articles

1. 1

   Marieke A. Vollebergh, Jos Jonkers, Sabine C. Linn. (2011) Genomic instability in breast and ovarian cancers: translation into clinical predictive biomarkers. Cellular and Molecular Life Sciences
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2. 2

   Avrum Z. Bluming, Carol Tavris. (2009) Hormone Replacement Therapy: Real Concerns and False Alarms. The Cancer Journal 15:2, 93-104
   CrossRef

3. 3

   Sophie Christin-Maitre. (2008) The role of hormone replacement therapy in the management of premature ovarian failure. Nature Clinical Practice Endocrinology & Metabolism 4:2, 60-61
   CrossRef

4. 4

   (2007) Current awareness: Pharmacoepidemiology and drug safety. Pharmacoepidemiology and Drug Safety 16:7, i-xii
   CrossRef