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Patients with known gBRCA-PV status receiving at least 8 weeks of maintenance PARPi were followed to assess MDS-related and AML-related postcytotoxic therapy events during and after treatment. Among 166 participants, a higher proportion of MDS/AML events occurred in gBRCA-PV carriers, especially MDS-pCT, supporting an increased risk after PARPi in recurrent settings.",{"@graph":69,"@context":126},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/germline-brca-pathogenic-variants-in-patients-with-ovarian-cancer-and-post-poly-adp-ribose-polymerase-inhibitor-myeloid-neoplasms-original-research/332471/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/germline-brca-pathogenic-variants-in-patients-with-ovarian-cancer-and-post-poly-adp-ribose-polymerase-inhibitor-myeloid-neoplasms-original-research/332471.png","ImageObject",300,407,{"name":92,"@type":93},"Levi","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-23","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118,122],{"name":109,"@type":110,"acceptedAnswer":111},"What was the study’s primary aim regarding gBRCA-PV status and PARPi treatment?","Question",{"text":112,"@type":113},"To investigate the occurrence of post-PARPi MDSs/AMLs-pCTs according to germline BRCA pathogenic variant status.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were patients selected for the retrospective single-center study?",{"text":117,"@type":113},"Patients with advanced high-grade ovarian carcinoma with known gBRCA-PV status who received at least 8 weeks of maintenance PARPi were included from February 2017 to December 2022.",{"name":119,"@type":110,"acceptedAnswer":120},"What did the study find about MDS-pCT and AML-pCT in gBRCA-PV carriers vs non-carriers?",{"text":121,"@type":113},"After a median follow-up of 40 months, 6% had MDS-pCT and 2% had AML-pCT overall; gBRCA-PV carriers showed a higher proportion of MDS-pCT (9% vs 1%) and MDS/AMLs-pCT (10% vs 2%).",{"name":123,"@type":110,"acceptedAnswer":124},"What clinical conclusion was drawn about risk after PARPi in ovarian cancer patients?",{"text":125,"@type":113},"Presence of a gBRCA-PV was associated with a higher risk of MDS-pCT and possibly myeloid neoplasms after PARPi, particularly in recurrent disease.","https://schema.org",{"og:url":83,"og:type":128,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":130,"canonical":83},"index,follow",{"doc_id":132,"site_id":62},332471,1790161507,{"code":4,"msg":5,"data":135},{"doc_id":132,"user_id":136,"nickname":92,"user_avatar":137,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":138,"file_id":139,"file_url":140,"file_type":141,"file_size":142,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":34,"language":143,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":144,"faqs":145,"seo_title":146,"seo_description":67,"update_tm":147,"read_time":148,"preview_page_count":4},7971461740909,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","ORIGINAL RESEARCH  \nGermline BRCA pathogenic variants in patients with ovarian cancer and post-poly (ADP-ribose) polymerase inhibitor myeloid neoplasms  \nC. Valenza1, 2y, M. Mongillo3y, F. Gigli4, D. Trapani1, 2, J. Katrini1, 2, E. Nicolò1, 2, L. Boldrini1, 2, L. Boscolo Bielo1, 2,  \nG. Castellano1 , 2, L. Guidi1, 2, G. Pellizzari1, 2, S. Derio3, M. Lapresa3, G. Parma3, E. Derenzini4, G. Curigliano1, 2 &  \nN. Colombo3, 5 􀀂  \n1Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan; 2Department of Oncology and HematoOncology, University of Milan, Milan; 3Division of Gynecologic Oncology, European Institute of Oncology, IRCCS, Milan; 4Division of Haematology Oncology, European Institute of Oncology, IRCCS, Milan; 5Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy  \nAvailable online xxx  \nBackground: Among patients with advanced high-grade ovarian carcinoma (aHGOC) treated with poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis), the presence of a germline BRCA pathogenic variant (gBRCA-PV) may increase the risk of bone marrow mutagenesis resulting in postcytotoxic therapy myelodysplastic neoplasms (MDSpCT) or acute myeloid leukemia (AML-pCT), as it is expressed in heterozygosity also by hematopoietic progenitors. We aimed to investigate the occurrence of post-PARPi MDSs/AMLs-pCTs according to gBRCA-PV status.  \nPatients and methods: We conducted a retrospective single-center study to evaluate MDS/AML-pCT in patients with aHGOC and a known gBRCA-PV status receiving at least 8 weeks of maintenance PARPi, in any line of therapy, from February 2017 to December 2022 . The endpoint was the proportion of patients who experienced MDSs-pCT and AMLs-pCT during and after treatment with PARPi, in gBRCA-PV carriers and non-carriers.  \nResults: A total of 166 patients were included: 95 (57%) had a gBRCA-PV and 72% received PARPi for recurrent disease. The number of lines of chemotherapies before and after PARPi, median overall survival, and median follow-up were comparable between gBRCA-PV carriers and non-carriers. After a median follow-up of 40 .0 (95% confidence interval: 35.7-44.3) months, 10 (6%) patients were diagnosed with an MDS-pCT and 4 (2%) with an AML-pCT. A higher proportion of MDSs/AMLs-pCT (10% versus 2%; P ¼ 0. 16) and, in particular, of MDSs-pCT (9% versus 1%; P ¼ 0.04) was observed among gBRCA-PV carriers.  \nConclusions: The presence of a gBRCA-PV is associated with a higher risk of MDS-pCT and possibly of myeloid neoplasms after PARPi in patients with aHGOC who received PARPi, especially in the setting of recurrent disease. Key words: advanced high-grade ovarian carcinoma, germline BRCA pathogenic variant, myelodysplastic neoplasms, PARP inhibitors  \nINTRODUCTION  \nMyeloid neoplasms postcytotoxic therapy (MN-pCT) are clonal hematopoietic stem cell disorders that are diagnosed after exposure to cytotoxic therapies, including DNA damage repair (DDR) targeting agents, such as poly (ADPribose) polymerase inhibitors (PARPis) .1,2 MN-pCTs account for 10%-20% of all myeloid neoplasms and include myelodysplastic neoplasms (MDSs-pCT), myelodysplasticmyeloproliferative neoplasms, and acute myeloid leukemia  \n*Correspondence to: Prof. Nicoletta Colombo, Division of Gynecologic Oncology, European Institute of Oncology, IRCCS, Via Ripamonti 435, Milan 20141, Italy. Tel: þ390257489543  \nE-mail: [nicoletta.colombo@ieo.it](nicoletta.colombo@ieo.it) (N. Colombo).  \nyEqually contributed as cofirst authors.  \n2059-7029/© 2024 The Authors. Published by Elsevier Ltd on behalf of European Society for Medical Oncology. This is an open access article under the CC BY-NC-ND license ([http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/)).  \n(AML-pCT) . In terms of prognosis, MN-pCTs are lifethreatening diseases, characterized by a median life expectancy of 8 months, that is inferior to the same diseases occur","cbCaikueluqz8w0I","https://ap.wps.com/l/cbCaikueluqz8w0I","pdf",335038,"English","# Background\n# Patients and methods\n# Results\n# Conclusions\n# Introduction","[{\"question\":\"What was the study’s primary aim regarding gBRCA-PV status and PARPi treatment?\",\"answer\":\"To investigate the occurrence of post-PARPi MDSs/AMLs-pCTs according to germline BRCA pathogenic variant status.\"},{\"question\":\"How were patients selected for the retrospective single-center study?\",\"answer\":\"Patients with advanced high-grade ovarian carcinoma with known gBRCA-PV status who received at least 8 weeks of maintenance PARPi were included from February 2017 to December 2022.\"},{\"question\":\"What did the study find about MDS-pCT and AML-pCT in gBRCA-PV carriers vs non-carriers?\",\"answer\":\"After a median follow-up of 40 months, 6% had MDS-pCT and 2% had AML-pCT overall; gBRCA-PV carriers showed a higher proportion of MDS-pCT (9% vs 1%) and MDS/AMLs-pCT (10% vs 2%).\"},{\"question\":\"What clinical conclusion was drawn about risk after PARPi in ovarian cancer patients?\",\"answer\":\"Presence of a gBRCA-PV was associated with a higher risk of MDS-pCT and possibly myeloid neoplasms after PARPi, particularly in recurrent disease.\"}]","Germline BRCA pathogenic variants in patients with ovarian cancer and post-poly (ADP-ribose) polymerase inhibitor myeloid neoplasms - Original Research | PDF",1789998355,18]