\nDaniel Egle, Innsbruck<\/td>\n<\/tr>\n
\n(Click to enlarge)<\/em><\/td>\n
![\"ABCSG](\"https:\/\/www.abcsg.org\/wp\/wp-content\/uploads\/2025\/07\/61_Study-Design_20250618-scaled.jpg\")
<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\nTreatment:<\/h3>\n
Participants receive 4 weeks of Aromatase Inhibitors (AI) in the initial Run-in Phase, followed by 2:1 randomization in arm A or B or enrolment in arm C in the Main Treatment Phase, depending on ctDNA-concentration and Ki-67 value of the participant. CtDNA-concentration is measured centrally by Natera with the SignateraTM-test, for which an (archived) tumor sample and blood are shipped at the beginning of the study. Ki-67 is evaluated locally after 3 weeks of AI therapy in the Run-in Phase.<\/p>\n
If the measured ctDNA-concentration is max. 1 mean tumor molecule (MTM)\/mL prior to treatment start AND Ki-67 is \u226410% after 3 weeks of AI, the participant is randomized 2:1 in arm treatment A or B:<\/p>\n
- \n
- Arm A<\/strong>
\nAI for 6-8 months (+\/- 30 days) as per Standard of Care. Switch to tamoxifen is allowed, if AI is not tolerated.<\/li>\n- Arm B<\/strong>
\nChemotherapy as per Standard of Care for 8 months (+\/- 30 days)<\/li>\n<\/ul>\nParticipants, whose ctDNA-concentration prior to treatment start exceeds 1 MTM\/mL OR whose Ki-67 is > 10% after 3 weeks of AI will be enrolled in treatment arm C:<\/p>\n
- \n
- Arm C<\/strong>
\nChemotherapy as per Standard of Care for 8 months (+\/- 30 days)<\/li>\n<\/ul>\nPrimary Objective:<\/h3>\n
- \n
- To determine the efficacy of endocrine therapy vs chemotherapy in endocrine responsive patients with HR-positive, HER2-negative breast cancer and a ctDNA-concentration \u2264 1 MTM\/mL, measured by modified preoperative endocrine prognostic index (PEPI) score.<\/li>\n<\/ul>\n
Secondary Objectives:<\/h3>\n
- \n
- \nTo determine the efficacy of endocrine therapy vs chemotherapy in endocrine responsive patients with a ctNDA-concentration \u2264 1 MTM\/mL,measured by Residual Cancer Burden (RCB).\n<\/li>\n
- \nTo determine the difference in breast conservation turn-over rate (BCTOR) between endocrine therapy vs chemotherapy in endocrine responsive patients with a ctDNA-concentration \u2264 1 MTM\/mL.\n<\/li>\n
- \nTo determine the efficacy of endocrine therapy vs chemotherapy in endocrine responsive patients with a ctDNA-concentration \u2264 1 MTM\/mL measured by long-term outcome (invasive disease-free survival, invasive breast cancer-free survival, distant recurrence-free survival, and overall survival).\n<\/li>\n
- \nTo compare patient reported outcomes of neoadjuvant endocrine therapy vs chemotherapy in endocrine responsive patients with HR-positive, HER2-negative breast cancer and a ctDNA-concentration \u2264 1 MTM\/mL, measured by EORTC QLQ-C30 and QLQ-BR42.\n<\/li>\n
- \nTo compare patient reported outcomes of neoadjuvant chemotherapy in endocrine responsive patients with a ctDNA-concentration \u2264 1 MTM\/mL (arm B) vs chemotherapy in patients with a ctDNA-concentration > 1 MTM\/mL or non-endocrine responsive patients (arm C) with HR-positive, HER2-negative breast cancer, measured by EORTC QLQ-C30 and QLQ-BR42.\n<\/li>\n
- \nTo compare patient reported outcomes in patients receiving different adjuvant therapy measured by EORTC QLQ-C30 and QLQ-BR42 after 1-year of follow up from surgery.\n<\/li>\n<\/ul>\n
Safety Objectives:<\/h3>\n
- \n
- To determine the difference in Adverse Events (AEs) between endocrine therapy vs chemotherapy in endocrine responsive patients with a ctDNA-concentration \u2264 1 MTM\/mL.<\/li>\n<\/ul>\n
Exploratory Objectives:<\/h3>\n
- \n
- To evaluate the kinetics of ctDNA-detection across prespecified time points between treatment arms.<\/li>\n
- To evaluate the association of kinetics of ctDNA-detection with surgical and long-term outcome.<\/li>\n
- To determine the efficacy of endocrine therapy vs chemotherapy separately in patients with no detectable ctDNA vs patients with a ctDNA-concentration >0 to \u2264 1 MTM\/mL.<\/li>\n<\/ul>\n
Translational Objectives:<\/h3>\n
- \n
- To study additional research questions\/ to perform additional analyses from biological material and\/ or clinical data that have been collected within this study.<\/li>\n<\/ul>\n
Patient Population<\/h3>\n
- \n
- The target population of this study consists of patients with ER+\/HER2- early or locally advanced breast cancer (stage IIA-III per AJCC v8) with an indication for chemotherapy and no prior systemic breast cancer specific treatment.<\/li>\n
- Participants will receive treatment in the Main Treatment Phase based on their ctDNA-status, assessed at the beginning of the trial, measured centrally with the SignateraTM-test and their endocrine response, assessed through the Ki67-value after 3 weeks of initial AI therapy (for details refer to \u201eTreatment\u201c).<\/li>\n<\/ul>\n
* Study information is displayed as described in study protocol V2.0. Sites must adhere to the currently approved local version..<\/em><\/p>\n","protected":false},"excerpt":{"rendered":"
A prospective, randomized, controlled, open-label multicenter phase II study investigating neoadjuvant endocrine therapy versus chemotherapy in HR-positive, HER2-negative, , endocrine responsive early and locally advanced breast cancer with a ctDNA-concentration \u2264 1 MTM\/mL Study Start: Q3\/2025 Coordinating Investigators: Michael Gnant, Vienna Daniel Egle, Innsbruck Participants: 256 (national) Study Design: (Click to enlarge) Treatment: Participants receive […]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":38833,"menu_order":6,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"footnotes":"","_members_access_role":[],"_members_access_error":""},"tags":[],"class_list":["post-38840","page","type-page","status-publish","hentry"],"acf":[],"publishpress_future_action":{"enabled":false,"date":"2027-04-13 04:52:50","action":"delete","newStatus":"draft","terms":[],"taxonomy":"translation_priority","extraData":[]},"publishpress_future_workflow_manual_trigger":{"enabledWorkflows":[]},"_links":{"self":[{"href":"https:\/\/www.abcsg.org\/en\/wp-json\/wp\/v2\/pages\/38840","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.abcsg.org\/en\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.abcsg.org\/en\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.abcsg.org\/en\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.abcsg.org\/en\/wp-json\/wp\/v2\/comments?post=38840"}],"version-history":[{"count":3,"href":"https:\/\/www.abcsg.org\/en\/wp-json\/wp\/v2\/pages\/38840\/revisions"}],"predecessor-version":[{"id":42303,"href":"https:\/\/www.abcsg.org\/en\/wp-json\/wp\/v2\/pages\/38840\/revisions\/42303"}],"up":[{"embeddable":true,"href":"https:\/\/www.abcsg.org\/en\/wp-json\/wp\/v2\/pages\/38833"}],"wp:attachment":[{"href":"https:\/\/www.abcsg.org\/en\/wp-json\/wp\/v2\/media?parent=38840"}],"wp:term":[{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.abcsg.org\/en\/wp-json\/wp\/v2\/tags?post=38840"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}
- To study additional research questions\/ to perform additional analyses from biological material and\/ or clinical data that have been collected within this study.<\/li>\n<\/ul>\n
- To determine the difference in Adverse Events (AEs) between endocrine therapy vs chemotherapy in endocrine responsive patients with a ctDNA-concentration \u2264 1 MTM\/mL.<\/li>\n<\/ul>\n
- To determine the efficacy of endocrine therapy vs chemotherapy in endocrine responsive patients with HR-positive, HER2-negative breast cancer and a ctDNA-concentration \u2264 1 MTM\/mL, measured by modified preoperative endocrine prognostic index (PEPI) score.<\/li>\n<\/ul>\n
- Arm B<\/strong>