title: Genomic profile of endometrial tumors depends on morphological subtype, not on tamoxifen exposure.
abstract: Tamoxifen has been a very effective treatment for breast cancer for several decades, however, at the same time increases the risk of endometrial cancer, especially after prolonged exposure. In addition, tamoxifen has been associated with a higher proportion of unfavorable uterine tumor subtypes (carcinosarcomas and serous adenocarcinomas) with worse survival. We investigated whether endometrial tumors, which developed after prolonged tamoxifen treatment for breast cancer, are genetically different from endometrial tumors without preceding tamoxifen exposure. Array CGH was used on archival formalin-fixed paraffin embedded endometrial tumors to determine genomic aberrations. We compared the genomic profiles of 52 endometrial tumors from breast cancer patients after long-term (>or=2 years) tamoxifen use (endometrioid adenocarcinomas, n = 26; carcinosarcomas, n = 14; and serous adenocarcinomas, n = 12) with endometrial tumors from unexposed breast cancer patients (n = 45). Genomic profiles were correlated with tamoxifen exposure, tumor subtypes, and histopathological characteristics of the endometrial tumors. The common uterine corpus cancers of the endometrioid subtype show few genomic aberrations. Tumors with many genomic aberrations were in general ER-negative. In contrast, carcinosarcomas and serous adenocarcinomas showed many aberrations; however, they were indistinguishable from each other. Tumors that developed after prolonged tamoxifen use did not show more or different aberrations than unexposed tumors. This was true for all tumor subtypes. Thus, endometrial carcinomas that develop after prolonged tamoxifen use cannot be distinguished from nonusers on basis of their tumor genomic profile.
authors.affiliation: Department of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Renske
authors.initials: R
authors.lastname: Fles
authors.forename: Wilhelmina E
authors.initials: WE
authors.lastname: Hoogendoorn
authors.forename: Inge
authors.initials: I
authors.lastname: Platteel
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Scheerman
authors.forename: Gerie
authors.initials: G
authors.lastname: de Leeuw-Mantel
authors.forename: Marian J E
authors.initials: MJ
authors.lastname: Mourits
authors.forename: Harry
authors.initials: H
authors.lastname: Hollema
authors.forename: Flora E
authors.initials: FE
authors.lastname: van Leeuwen
authors.forename: Hester H
authors.initials: HH
authors.lastname: van Boven
authors.forename: Petra M
authors.initials: PM
authors.lastname: Nederlof
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D002296:Carcinosarcoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D016022:Case-Control Studies; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D016609:Neoplasms, Second Primary; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013629:Tamoxifen / Q000627:therapeutic use*; D046888:Tissue Array Analysis
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D013629:Tamoxifen