Eur. J. Gynaecol. Oncol. 2022; 43(1): 78–86 http://doi.org/10.31083/j.ejgo4301003 Copyright: © 2022 The Author(s). Published by IMR Press. This is an open access article under the CC BY 4.0 license. Publisher’s Note: IMR Press stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Review Efficacy of sonohysterography and hysteroscopy for evaluation of endometrial lesions in tamoxifen treated patients: a systematic review Federica Di Guardo 1, *, Giosuè Giordano Incognito 1 , Chiara Lello 2 , Gisella D’Urso 1 , Fortunato Genovese 1 , Marco Palumbo 1 1 Department of General Surgery and Medical Surgical Specialties, University of Catania, 95125 Catania, Italy 2 Department of Drug and Health Sciences, University of Catania, 95125 Catania, Italy *Correspondence: fediguardo@gmail.com (Federica Di Guardo) Academic Editor: Enrique Hernandez Submitted: 20 October 2021 Revised: 2 January 2022 Accepted: 5 January 2022 Published: 15 February 2022 Abstract Objective: This review aims to evaluate the incidence of endometrial lesions in tamoxifen-treated breast cancer patients identified by hysteroscopy (HS) and sonohysterography (SIS) and the diagnostic accuracy of the two methods to detect them. Methods: A systematic review of the literature concerning the role of HS and SIS for evaluation of the endometrium in tamoxifen-treated breast cancer patients was performed. We searched MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials, IBECS, BIOSIS, Web of Science, SCOPUS, congress abstracts, and Grey literature (Google Scholar; British Library). The search terms used were “hysteroscopy”, “hysterosonography”, “sonohysterography” combined with “tamoxifen”; 89 citations were identified and selected in the initial screen- ing. Results: 28 studies were included in the systematic review. There were 61 citations excluded because they were review articles (n = 9) or case report (n = 5) and non-English articles (n = 8), and had too little information in the full text (n = 39). Similar accuracy between SIS and HS in detection of endometrial tamoxifen-related lesions was found. Conclusions: SIS may represent a minimally invasive, simple, safe, well-tolerated and cost-effective alternative to HS, associated with few contraindications and no potential complications. Keywords: Hysteroscopy; Hysterosonography; Sonohysterography; Tamoxifen; Breast cancer 1. Introduction Tamoxifen is a nonsteroidal selective estrogen recep- tor modulator that is widely used for the treatment of es- trogen receptor-positive breast cancer patients [1,2]. Clin- ical trials have shown that long-term therapy for at least 5 years, is more effective than short-term treatment (<2 years). Although it acts as an antiestrogen in breast tissue [3], it has a partial agonist effect on other tissues, such as the endometrium and myometrium [4]; hence, prolonged ther- apy is associated with various uterine pathologies, includ- ing endometrial polyps, submucosal leiomyomas, endome- trial hyperplasia, and endometrial cancer [5–8]. However, literature background showed that the benefits achieved in breast cancer treatment, may overcome any potential uter- ine abnormalities that may occur [9]. In this scenario, it is emerging the necessity to develop adequate methods to diagnose endometrial complications. Nevertheless, the op- timal method of surveillance has not yet been determined [6,9–11]. Transvaginal sonography (TVS) is the imaging tech- nique of choice for first-line investigation of intrauterine abnormalities [12–14]. This procedure is relatively pain- less, well accepted by patients, and can be easily performed by the gynecologist at a relatively low cost [15]. Nev- ertheless, several studies reported a limited value of TVS in tamoxifen-treated patients due to false-negative [16] as well as false positive results [10,15] and proposed addi- tional diagnostic procedures, such as hysteroscopy (HS) or transvaginal saline infusion sonohysterography (SIS). HS, combined with histological examination of an en- dometrial aspiration or biopsy, remains the current gold standard for uterine cavity assessment [16–19]. More- over, it represents a highly effective therapeutic approach to treat various conditions [20] and it can be useful to assess their eventual recurrence [21]. However, discomfort due to anatomical impediments may represent a cause of office hysteroscopy failure, requiring the necessity for anesthesia and operating theater [22]; a fact that increases both risks and costs. Furthermore, it should be performed by a gyne- cologist with enough facilities and expertise [23]. In the last 20 years, several studies have proposed the use of SIS, as a less invasive alternative to HS [22,23]. In- deed, it is an affective “add-on” to TVS which involves the use of slow instillation of sterile saline solution into the en- dometrial cavity through a 5-French catheter under contin- uous TVS guidance, providing both a contrast medium and an expanding agent [24]. Along this line, sensitivity, speci- ficity, and predictive values of SIS are clearly superior in comparison to TVS. Moreover, SIS is associated with min- imal discomfort and lower costs, being easily performed by most of gynecologists [25–29]. With regards to con- traindications, only few has been reported in literature [30] eventually leading to no potential complications. Finally, it can accurately differentiate focal lesions such as polyps and