English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

Uterine carcinosarcoma/malignant mixed Mullerian tumor (UC/MMMT) is an uncommon and aggressive gynecological malignancy with poor prognosis. Tumors arise from monoclonal carcinoma cells derived from embryonal mesoderm, which exhibit sarcomatous metaplasia. UC/MMMT usually occurs in postmenopausal women and accounts for 2%-5% of all uterine malignancies [1,2]. The five-year survival rates are particularly poor (21%-39%). Several case reports and case series describe UC/MMMT occurring after tamoxifen therapy for breast cancer [3,4,5,6,7,8,9]. Retrospective studies suggest that the increased incidence of these high-risk malignancies is greater than the observed increase in incidence of endometrial tumors generally following tamoxifen therapy [10,11,12,13], though the number of subjects with UC/MMMT in any of these studies is small. The increase in uterine cancers generally following tamoxifen therapy is thought to be driven by the estrogen receptor alpha (ERα) through a positive trophic effect on the uterine corpus. Although tamoxifen binds ERβ with equal affinity, there is no observed activation of this receptor [14,15]. Whether ER activation exerts any positive effect on UC/MMMTs remains equivocal. Other studies suggest that tamoxifen may upregulate expression of the HER2/neu oncogene in UC/MMMT cells [16,17], although any potential effect on the behavior of these malignancies is far from clear. As tamoxifen metabolites can covalently bind DNA, principally forming (E)- and (Z)-α-(deoxyguanosin-N2-yl)-4-hydroxytamoxifen adducts [18], the possibility that tamoxifen therapy is inherently carcinogenic has also been considered. However, tamoxifen-DNA adduct formation in uterine tissues following oral administration occurs at levels too low to be consistent with this being the mechanism driving such endometrial cancers [19].  We identified two unrelated women who developed UC/MMMT as a second primary malignancy following BRCA1-associated breast cancer. Neither of these women received hormone therapy, as their tumors were histologically determined to be unresponsive to hormone therapy (i.e., ER-/progesterone receptor [PR]-). Patient 1 had BRCA1 c.5503C>T (p.Arg1835*), developed breast cancer at 36 years, which was managed with lumpectomy and local radiotherapy, and subsequently developed UC/MMMT at 48 years. Patient 2 had BRCA1 c.2560_2561dupGC (p.Gln855fs), developed breast cancer at 34 years, again treated with lumpectomy and local radiotherapy, and was found to have UC/MMMT at 56 years. Although BRCA1 mutation carriers are at increased risk of developing endometrial cancers compared to the general population, most of this risk is attributable to tamoxifen use [20]. It has also been suggested that BRCA1 mutations may predispose carriers to uterine papillary serous carcinoma specifically [21,22]. However, UC/MMMT is not recognized as part of the BRCA1 phenotype. Prompted by this unexpected finding, we conducted a retrospective population-based study to establish whether an association exists between breast cancer and UC/MMMT generally and whether a breast tumor being ER-/PR- has any bearing on this.

Uterine carcinosarcoma/malignant mixed Müllerian tumor incidence is increased in women with breast cancer, but independent of hormone therapy