[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-371552-105":59,"doc-detail-371552-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","window-of-opportunity-trials-to-screen-effective-agents-and-optimize-dose-in-breast-cancer-prevention","Window-of-opportunity trials to screen effective agents and optimize dose in breast cancer prevention","","Window-of-opportunity trials are evaluated as a study pathway to identify effective preventive agents and refine dosing strategies for breast cancer risk reduction. The article reviews evidence for using short pre-surgical trials to assess tissue drug bioavailability, pharmacokinetics, and biological activity. Low-dose tamoxifen is discussed as a WOO approach followed by phase III validation, and similar efforts with low-dose exemestane are introduced. Preventive therapy is contextualized through endocrine mechanisms, biomarker readouts such as Ki-67, and considerations of dose intensity versus efficacy and toxicity.",{"@graph":69,"@context":122},[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":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/window-of-opportunity-trials-to-screen-effective-agents-and-optimize-dose-in-breast-cancer-prevention/371552/",{"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/window-of-opportunity-trials-to-screen-effective-agents-and-optimize-dose-in-breast-cancer-prevention/371552.png","ImageObject",300,407,{"name":92,"@type":93},"Quinn Holloway","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-24","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the purpose of window-of-opportunity (WOO) trials in breast cancer prevention?","Question",{"text":112,"@type":113},"WOO trials aim to screen candidate preventive agents and optimize dose by evaluating tissue bioavailability, pharmacokinetics, and biological drug activity in a short pre-surgical setting.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How was low-dose tamoxifen evaluated in a WOO trial?",{"text":117,"@type":113},"Low-dose tamoxifen was studied through WOO trials and later validated in phase III. Comparisons of 5 mg/day versus 20 mg/day showed similar effects on proliferation measured by Ki-67 labeling index.",{"name":119,"@type":110,"acceptedAnswer":120},"Which biomarkers are emphasized for assessing preventive activity?",{"text":121,"@type":113},"The article highlights Ki-67 labeling index and biomarker changes related to carcinogenesis to infer preventive activity and treatment effects.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},371552,1790334947,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":34,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":52,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},2336474466712,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","npj | breast cancer Review article  \nPublished in partnership with the Breast Cancer Research Foundation  \n[https://doi.org/10.1038/s41523-025-00745-8](https://doi.org/10.1038/s41523-025-00745-8)  \nWindow-of-opportunity trials to screen effective agents and optimize dose in breast cancer prevention  \n Check for updates  \nG. Aurilio1, D. Serrano  1, M. Lazzeroni1, A. Guerrieri-Gonzaga  1, H. Johansson  1, S. Gandini2,  \nI. M. Briata 3, M. D’Amico3, S. Spinaci4, P. Veronesi5,6, V. Galimberti5, M. Intra5, B. M. Heckman-Stoddard7, E. Szabo 7, G. Viale8,9, B. Bonanni 1 & A. DeCensi 3   \nWindow-of-opportunity trials are a path to screen effective agents and optimize dose in breast cancer risk reduction. We review thescientific evidence regarding the utility of window-of-opportunity trials to screen effective agents and optimize dose for successful risk reduction/interception of breast cancer. Low-dose tamoxifen was evaluated in a window-of-opportunity trial and then validated in a phase-III trial. We are now studying similar activity with low-dose exemestane.  \nPreventive therapy or chemoprevention is a medical approach aimed at reducing the risk of common tumors and is particularly studied in the field of breast cancer. This term was coined by Michael Sporn to define the inhibition or reversal of carcinogenesis by the use of noncytotoxic nutrients or pharmacologic compounds that protect against the development and progression of mutant clones of malignant cells1–3. Currently, preventive therapy is a recognized useful measure to effectively reduce the incidence of breast cancer4, the most commonly diagnosed cancer in female patients, accounting for 23.8% of total female cases5.  \nSeveral endocrine therapies used in the adjuvant setting of breast cancer patients have been approved for prevention6,7.  \nTamoxifen is a well-established selective estrogen receptor (ER) modulator widely used to manage ER-positive breast cancer patients ata standard dose of 20 mg a day, with a benefit in reducing mortality in the adjuvant setting8. In rat models, tamoxifen induced long-lasting chemopreventive action on chemically-induced breast cancer, both benign tumors and cancers9, 10. However, due to its partial estrogenic activity in the uterus and on platelets, tamoxifen use is associated with an increased risk of endometrial tumors and venous thromboembolicevents.  \nWindow of opportunity (WOO) trials area very useful study design to evaluate, ex vivo, several aims. Among these, are tissue drug bioavailability, pharmacokinetic, and biological drug activity. In particular, our main interest is focused on investigating novel strategies for preventive therapy. To examine if efficacy could be maintained while reducing the dose, tamoxifen has been studied through WOO trials, which are pre-surgical studies of short duration used to screen the  \npreventive role ofcandidate drugs and better define their optimal dosing. In ER-positive breast cancer patients, our group randomly assessed different tamoxifen doses in a WOO trial and showed comparability of 5 mg/day versus 20 mg/day in decreasing proliferation as measured by the Ki-67 labeling index (LI)11. Breast intraepithelial neoplasia (IEN) is apart of breast cancer landscape encompassing different histological forms, such as atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS) . Overall, women with these precancerous lesions have a 5–10 times higher risk of developing invasive breast cancer forms compared with the general population, and these lesions account for 15–25% of all breast tumors in the current era of screening mammography12. As illustrated in the Fig. 1 the WOO trials provide the chance to study the drug activity not only on the tumor tissue, but also on the adjacent DCIS/LCIS and ADH, when present, and in the normal tissue. This proved to bean important objective to elucidate the potential preventive activity by me","cbCaibaF3kQK1vIV","https://ap.wps.com/l/cbCaibaF3kQK1vIV","pdf",1527951,"English","# Preventive therapy and rationale\n## Window-of-opportunity trial design\n## Tamoxifen evidence and dosing\n## Exemestane and future directions\n## Biomarkers and field cancerization model","[{\"question\":\"What is the purpose of window-of-opportunity (WOO) trials in breast cancer prevention?\",\"answer\":\"WOO trials aim to screen candidate preventive agents and optimize dose by evaluating tissue bioavailability, pharmacokinetics, and biological drug activity in a short pre-surgical setting.\"},{\"question\":\"How was low-dose tamoxifen evaluated in a WOO trial?\",\"answer\":\"Low-dose tamoxifen was studied through WOO trials and later validated in phase III. Comparisons of 5 mg/day versus 20 mg/day showed similar effects on proliferation measured by Ki-67 labeling index.\"},{\"question\":\"Which biomarkers are emphasized for assessing preventive activity?\",\"answer\":\"The article highlights Ki-67 labeling index and biomarker changes related to carcinogenesis to infer preventive activity and treatment effects.\"}]","Window-of-opportunity trials to screen effective agents and optimize dose in breast cancer prevention | PDF",1790192316,25]