Reply to the Letter to the Editor on "Third generation aromatase inhibitors may prevent endometrial growth and reverse tamoxifen-induced uterine changes in postmenopausal breast cancer patients", by I. Cohen Ann Oncol 2005; 16: 1399

We thank Dr Cohen for his interest in our study and his useful comments. The first issue raised is the probability that the decrease in endometrial thickness and uterine volume in patients receiving aromatase inhibitors is due to the discontinuation of tamoxifen treatment and not a direct effect of aromatase inhibitors. As we mentioned in our article [1Go], future clinical trials looking at the endometrial safety of endocrine treatments, particularly those trials involving sequential treatments with selective estrogen receptor modulators and aromatase inhibitors, should also take into account the potential effect on the uterus of a wash-out period after tamoxifen treatment. Only then can we determine whether tamoxifen-induced changes would eventually resolve over time or whether aromatase inhibitors can offer a protective effect on the endometrium of patients treated with tamoxifen. While there are data on how endometrial thickness decreases over time following discontinuation of tamoxifen treatment [2Go], a direct comparison with the decrease achieved in patients receiving aromatase inhibitors is not available. Likewise, whether a difference in uterine effects between steroidal and non-steroidal aromatase inhibitors exists or whether there is a difference between the three agents is not known. Furthermore, the potential of aromatase inhibitors to reverse tamoxifen-induced uterine changes should be confirmed through randomized clinical trials. Recently, the Intergroup Exemestane Study presented data similar to ours, showing the decrease in endometrial thickness and uterine volume in women receiving exemestane compared with tamoxifen [3Go].

The second issue raised by Cohen is whether the polyps visualized by transvaginal sonography in the present study were real endometrial polyps and not subendometrial fibroids. In our institution, color Doppler imaging is routinely performed to confirm the presence of a polyp. In a prospective observational study on 3099 consecutive patients referred for the assessment of the endometrium and myometrium, 182 polyps were detected and 139 of them had a clear feeding vessel. A distinct vascular pedicle from the myometrium reaching at least the middle of the endometrium (called the ‘pedicle artery sign’) was related to the presence of a polyp in 81% of the patients, or to any focal lesion in 94.2% of cases [4Go]. We also reported that this sign was observed in 32 of 687 patients without an endometrial polyp. However, 22 of the 32 patients with false-positive results had other intracavitary pathology: submucous fibroids (7%), hyperplasia (2.9%), endometrial cancer (1.8%) and persistent trophoblastic tissue (1.2%). Only in 5.8% of the patients with a positive test was the cavity normal. These findings were very similar for 310 tamoxifen-treated patients, where the ‘pedicle artery test’ had a sensitivity for detecting polyps of 89%, specificity of 86%, positive predictive value of 85% and negative predictive value of 89%. Overall accuracy was 87% [5Go]. In addition to the presence of a feeding vessel, the characteristic appearance of a Swiss-cheese pattern and the ‘bright edge of the polyp’ were all considered to confirm the presence of a polyp versus a uterine fibroid. Therefore, we might safely assume that the vast majority of the presumed polyps in the present study were real polyps, and that only a small proportion may have been fibroids rather than polyps.

R. Paridaens1,2,*, L. Morales1,3, P. Neven2,3, D. Timmerman3 On behalf of all co-authors of the original article

Departments of 1 Medical Oncology and 3 Obstetrics and Gynecology, 2 Multidisciplinary Breast Center, University Hospital Gasthuisberg KU Leuven, Herestraat 49, 3000 Leuven, Belgium

(* Email: robert.paridaens{at}uz.kuleuven.ac.be)

References

1. Morales L, Timmerman D, Neven P et al. Third generation aromatase inhibitors may prevent endometrial growth and reverse tamoxifen-induced uterine changes in postmenopausal breast cancer patients. Ann Oncol 2005; 16: 70–74.[Abstract/Free Full Text]

2. Cohen I, Beyth Y, Azaria R et al. Ultrasonographic measurements of endometrial changes following discontinuation of tamoxifen treatment in postmenopausal breast cancer patients. Br J Obstet Gynecol 2000; 107: 1083–1087.[ISI]

3. Bertelli G, Hall E, Bliss J et al. Intergroup Exemestane Study: Results of the endometrial sub-protocol. Breast Cancer Res Treat 2004; 88 (Suppl 51): S35 (Abstr 402).

4. Timmerman D, Verguts J, Konstantinovic ML et al. The pedicle artery sign based on sonography with color Doppler imaging can replace second-stage tests in women with abnormal vaginal bleeding. Ultrasound Obstet Gynecol 2003; 22: 166–171.[ISI][Medline]

5. Timmerman D, Morales L, Konstantinovic ML et al. Evaluation of endometrial pathology in tamoxifen-treated breast cancer patients: the value of the ‘pedicle artery test’ using transvaginal color Doppler imaging. Int J Gynecol Cancer 2003; 13 (Suppl 1): 67 (Abstr 104).[CrossRef][ISI][Medline]





This Article
Full Text (PDF)
All Versions of this Article:
16/8/1402-a    most recent
mdi237v1
E-letters: Submit a response
Alert me when this article is cited
Alert me when E-letters are posted
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in ISI Web of Science
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Disclaimer
Request Permissions
Google Scholar
Articles by Paridaens, R.
PubMed
PubMed Citation
Articles by Paridaens, R.