Should ultrasound assessment of the endometrium be necessary in patients treated with Tamoxifen?

Tamoxifen is a nonsteroidal selective estrogen receptor modulator that is used mainly for adjuvant treatment of estrogen receptor-positive breast cancer. However, tamoxifen, due to its estrogen-mimicking effects, has been linked to various uterine conditions including menstrual irregularities, and endometrial c ancer. Considering that in women taking tamoxifen, ultrasonographical endometrial thickness can be increased without an underlying pathology and that the tamoxifen induces only an extra endometrial cancer in 1 per 1000 women per year of use, patients undergoing tamoxifen treatment don't typically undergo regular examinations of the endometrium, including ultrasonography. Routine ultrasonographic screening for endometrial lesions could result in excessive intervention for non-symptomatic endometrial conditio ns, undue stress, and might even negatively affect patients' adherence to tamoxifen therapy, which is crucial for reducing breast cancer recurrence and mortality. Nevertheless, if any unusual bleeding arises, an endometrial evaluation is necessary.

tamoxifen, endometrial thickness, ultrasound, breast cancer Publisher note : PHARMAKON-Press stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Copyright: © 2024 by the authors. Licensee PHARMAKON-Press, Athens, Greece. This is an open access article published under the terms and conditions of the Creative Commons Attribution (CC BY) license. Tamoxifen is a nonsteroidal selective estrogen receptor modulator that is used mainly for adju- vant treatment of estrogen receptor -positive breast cancers in premenopausal women [1] and as chemoprevention in patients at increased risk for breast cancer [2]. In premenopausal patients, the effect of ta - moxifen on the hypothalamic -pituitary-ovarian axis is similar to clomiphene, increasing follicle- stimulating hormone (FSH) and estradiol levels, and in those women having abnormal uterine bleeding, up to 23 percent will be found to have underlying (benign) endometrial pathology. In postmenopausal women, tamoxifen exerts a strong estrogenic effect that can stimulate en - dometrial proliferation and DNA damage [2]. How to cite this article: Iatrakis G., Zervoudis S., Sarella A., Tsikouras P., Paschopoulos M., Balafouta M., Peitsidis P. Should ultrasound assessment of the endometrium be necessary in patients treated with Tamoxifen? Rev. Clin. Pharmacol. Pharmacokinet. Int. Ed. 38 (1): 7-9 (2024). https://doi.org/10.61873/OEFM7580 8 REVIEW OF CLINICAL PHARMACOLOGY AND PHARMACOKINETICS, INTERNATIONAL EDITION 2024 Unlike raloxifene, tamoxifen has been linked to various uterine conditions such as menstrual irregularities, blood clots, uterine sarcoma, uter- ine carcinosarcoma [2], and endometrial thick - ening, fibroids, polyps, and endometrial cancer due to its estrogen -mimicking effects [3]. How- ever, tamoxifen induces only an extra endome- trial can cer in 1 per 1000 women per year of use, with en dometrial cancer being extremely rare in asympto matic premenopausal patients [4]. Thus, patients under going tamoxifen treat - ment don't typically un dergo regular examina - tions of the endometrium, including ultrasonog- raphy [5] and the American College of Obstetri- cians and Gynecologists (ACOG) endorses against screening asymptomatic patients on ta - moxifen for endometrial cancer [6]. On the con- trary, some authors recommend the assess - ment of thickened endometrium in tamoxifen therapy [7]. Tamoxifen typically induces sub-endometrial cysts at ultrasonography which correspond to cystically dilated endometrial glands at histology [8], although an atrophic endometrium could be discovered in some cases. Furthermore, tamoxifen is associated with endometrial polyps (ultraso- nographically discovered) which are not precur- sors of malignancy, and a large proportion of ta- moxifen users, without endometrial pathology at the start, will develop such subclinical lesions [8]. Nevertheless, if any unusual bleeding arises, an endometrial evaluation is necessary due to the marginally heightened risk of endometrial cancer associated with ta moxifen. More than half of premenopausal patients and up to a quarter of postmenopausal patients on tamoxifen thera py experience abnormal uterine bleeding [9]. This condition necessitates further investigation. Endo- metrial biopsy or Hysteroscopy with curettage is imperative in most cases [7]. Furthermore, the first procedure has generally replaced the need for diagnostic dilation and curettage. The point is to be sure that there is no endo- metrial cancer [10]. Nevertheless, the presence of spotting as a clinical symptom is crucial to pro- pose more investigation. One difficulty of diagno- sis that could hide an endometrial cancer occurs in patients with very tight or closed cervix [11]. As a conclusion, conducting routine ultraso- nographic screenings for endometrial lesions in asymptomatic patients on tamoxifen could result in excessive intervention for non -symptomatic endometrial conditions, undue stress, and might even negatively affect patients' adherence to ta- moxifen therapy, which is crucial for reducing breast cancer recurrence and mortality. CONFLICT OF INTEREST STATEMENT The authors declare no conflicts of interest.

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