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Original Article
- Uterine Malignant Mixed Müllerian Tumors Following Treatment with Selective Estrogen Receptor Modulators in Patients with Breast Cancer: A Report of 13 Cases and Their Clinicopathologic Characteristics
- Byung-Kwan Jeong, Chang O. Sung, Kyu-Rae Kim
- J Pathol Transl Med. 2019;53(1):31-39. Published online December 18, 2018
- DOI: https://doi.org/10.4132/jptm.2018.11.16
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- 2 Web of Science
- 4 Crossref
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Abstract
PDF - Background
Breast cancer treatment with selective estrogen receptor modulators (SERMs) increasesthe incidence of uterine malignant mixed Müllerian tumors (uMMMTs). We examine clinicopathologiccharacteristics and prognosis of SERM-associated uMMMTs (S-uMMMTs) and discusspossible pathogenetic mechanisms.
Methods
Among 28,104 patients with breast cancer, clinicopathologicfeatures and incidence of uMMMT were compared between patients who underwentSERM treatment and those who did not. Of 92 uMMMT cases that occurred during the same period,incidence, dose, and duration of SERM treatment, as well as overall survival rate, were comparedfor patients with breast cancer who underwent SERM treatment and those who did not (S-uMMMTvs NS-uMMMT) and for patients without breast cancer (de novo-uMMMT). Histopathologicalfindings and immunophenotypes for myogenin, desmin, p53, WT-1, estrogen receptor (ER) α, ERβ,progesterone receptor, and GATA-3 were compared between S-uMMMT and de novo-uMMMT.
Results
The incidence of S-uMMMT was significantly higher than that of NS-uMMMT (6.35-fold).All patients with SERM were postmenopausal and received daily 20–40 mg SERM. CumulativeSERM dose ranged from 21.9 to 73.0 g (mean, 46.0) over 39–192 months (mean, 107). Clinicopathologicfeatures, such as International Federation of Gynecology and Obstetrics stage andoverall survival, were not significantly different between patients with S-uMMMT and NS-uMMMTor between patients with S-uMMMT and de novo-uMMMT. All 11 S-uMMMT cases available forimmunostaining exhibited strong overexpression/null expression of p53 protein and significantlyincreased ERβ expression in carcinomatous and sarcomatous components.
Conclusions
SERMtherapy seemingly increases risk of S-uMMMT development; however, clinicopathologic featureswere similar in all uMMMTs from different backgrounds. p53 mutation and increased ERβ expressionmight be involved in the etiology of S-uMMMT. -
Citations
Citations to this article as recorded by
- Uterine carcinosarcomas: A case series of 9 cases from a low-income country
Boubacar Efared, Halidou Hamadou Koura, Aïchatou Balaraba Abani Bako, Idrissa Boubacar, Habiba Salifou Boureima, Garba Mahamadou, Hassan Nouhou
Medicine.2024; 103(40): e39773. CrossRef - Uterine carcinosarcoma: Unraveling the role of epithelial‐to‐mesenchymal transition in progression and therapeutic potential
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The FASEB Journal.2024;[Epub] CrossRef - Tamoxifen/toremifene
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Cancers.2019; 11(7): 964. CrossRef
- Uterine carcinosarcomas: A case series of 9 cases from a low-income country
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