Do drugs that stimulate ovulation increase the risk for endometrial stromal sarcoma?

Olaf Reich1,3 and Sigrid Regauer2

Departments of 1 Obstetrics and Gynecology and 2 Institute of Pathology, Medical University of Graz, Austria

3 To whom correspondence should be addressed. Email: olaf.reich{at}meduni-graz.at

Sir,

We read with interest the epidemiological study by Brinton et al. (2004)Go, which reports a statistically significant risk for invasive breast cancers after clomiphene citrate treatment. Overall reports on the pathogenetic influence of infertility treatment on breast cancer risk are conflicting (Gauthier et al., 2004Go). We report our data on ovulation-stimulating drugs in women with endometrial stromal sarcoma (ESS), a hormone-sensitive tumor of young women that accounts for <0.2% of gynaecological malignancies. The great majority of ESS express estrogen receptors, progesterone receptors, gonadotropin-releasing-hormone receptors, and aromatase (Reich and Regauler, 2000Go, 2004a,b). Among 64 patients with ESS who we are studying, eight (12.5%) had undergone in vitro fertilization treatment including clomiphene. To our knowledge this is the first such observation in a large patient group with ESS.

We would like bring attention to a possible association between the treatment with clomiphene citrate and the development of ESS. This is potentially important because patients with ESS are premenopausal, have an incidence of concomitant breast cancer, and often have a family history of hormone-sensitive cancers (personal observation). We speculate that some of these patients may be carriers of a genetic abnormality which influences endocrine signalling, as described for familial breast and prostate cancer. Such carriers would be at an increased risk of hormone-dependent neoplasms during or after treatment with ovulation-stimulating drugs.

References

Brinton LA, Scoccia B, Moghissi KS et al. (2004) Breast cancer risk associated with ovulation-stimulating drugs. Hum Reprod 19, 2005–2013.[Abstract/Free Full Text]

Gauthier E, Paoletti X and Clavel-Chapelon F (2004) Breast cancer risk associated with being treated for infertility: results from the French E3N cohort study. Hum Reprod 19, 2216–2221.[Abstract/Free Full Text]

Reich O and Regauer S (2004a) Aromatase expression in low-grade endometrial stromal sacromas: an immunohistochemical study. Mod Path 17, 104–108.[ISI][Medline]

Reich O, Nogales FF and Regauer S(2004b) Gonadotropin-releasing hormone receptor expression in endometrial stromal sarcomas: an immunohistochemical study. Mod Pathol, Oct 29. Epub ahead of print].

Reich O, Regauer S, Urdl M et al. (2000) Estrogen and progesterone receptors in low-grade endometrial stromal sarcomas. Br J Cancer 82, 1030–1034.[CrossRef][ISI][Medline]





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