Endocrine Therapy Response and 21-Gene Expression Assay for Therapy Guidance in HR+/HER2- Early Breast Cancer.

Autor: Nitz UA; West German Study Group, Moenchengladbach, Germany.; Ev. Bethesda Hospital, Breast Center Niederrhein, Moenchengladbach, Germany., Gluz O; West German Study Group, Moenchengladbach, Germany.; Ev. Bethesda Hospital, Breast Center Niederrhein, Moenchengladbach, Germany.; University Clinics Cologne, Women's Clinic and Breast Center, Cologne, Germany., Kümmel S; West German Study Group, Moenchengladbach, Germany.; Breast Unit, Kliniken Essen-Mitte, Essen, Germany.; Clinic for Gynecology with Breast Center, Charité-Universitätsmedizin Berlin, Berlin, Germany., Christgen M; Medical School Hannover, Institute for Pathology, Hannover, Germany., Braun M; Department of Gynecology, Breast Center, Red Cross Hospital Munich, Munich, Germany., Aktas B; University Clinics Essen, Women's Clinic, Essen, Germany.; University Clinics Leipzig, Women's Clinic, Leipzig, Germany., Lüdtke-Heckenkamp K; Niels Stensen Clinics, Clinics for Oncology, Osnabrück, Germany., Forstbauer H; Oncology Practice Network Troisdorf, Troisdorf, Germany., Grischke EM; University Clinics Tübingen, Women's Clinic, Tuebingen, Germany., Schumacher C; St Elisabeth Hospital, Cologne, Germany., Darsow M; Luisenhospital Duesseldorf, Practice for Senologic Oncology, Duesseldorf, Germany., Krauss K; University Clinics Aachen, Women's Clinic, Aachen, Germany., Nuding B; Ev. Hospital Bergisch Gladbach, Bergisch Gladbach, Germany., Thill M; Markus Hospital, Breast Center, Frankfurt, Germany., Potenberg J; Ev. Waldkrankenhaus Berlin, Berlin, Germany., Uleer C; Gynecologists at Bahnhofsplatz, Hildesheim, Germany., Warm M; City Hospital Holweide, Breast Center, Cologne, Germany., Fischer HH; Ev. Hospital Gelsenkirchen, Gelsenkirchen, Germany., Malter W; University Clinics Cologne, Women's Clinic and Breast Center, Cologne, Germany., Hauptmann M; Institute of Biostatistics and Registry Research, Brandenburg Medical School Theodor Fontane, Neuruppin, Germany.; Faculty of Health Sciences, Joint Faculty of the Brandenburg University of Technology Cottbus - Senftenberg, the Brandenburg Medical School Theodor Fontane and the University of Potsdam, Neuruppin, Germany., Kates RE; West German Study Group, Moenchengladbach, Germany., Gräser M; West German Study Group, Moenchengladbach, Germany.; Ev. Bethesda Hospital, Breast Center Niederrhein, Moenchengladbach, Germany.; Department of Gynecology, University Medical Center Hamburg, Hamburg, Germany., Würstlein R; Breast Center, Department of Obstetrics and Gynecology and CCC Munich, LMU University Hospital, Munich, Germany., Shak S; Exact Science, Inc, Redwood City, CA., Baehner F; Exact Science, Inc, Redwood City, CA., Kreipe HH; Medical School Hannover, Institute for Pathology, Hannover, Germany., Harbeck N; West German Study Group, Moenchengladbach, Germany.; Breast Center, Department of Obstetrics and Gynecology and CCC Munich, LMU University Hospital, Munich, Germany.
Jazyk: angličtina
Zdroj: Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2022 Aug 10; Vol. 40 (23), pp. 2557-2567. Date of Electronic Publication: 2022 Apr 11.
DOI: 10.1200/JCO.21.02759
Abstrakt: Purpose: To our knowledge, WSG-ADAPT-HR+/HER2- (ClinicalTrials.gov identifier: NCT01779206; n = 5,625 registered) is the first trial combining the 21-gene expression assay (recurrence score [RS]) and response to 3-week preoperative endocrine therapy (ET) to guide systemic therapy in early breast cancer.
Materials and Methods: Baseline and postendocrine Ki67 (Ki67 post ) were evaluated centrally. In the endocrine trial, all patients received exclusively ET: patients with pathologic regional lymph node status (pN) 0-1 (ie, 0-3 involved lymph nodes) entered control arm if RS ≤ 11 and experimental arm if RS12-25 with ET response (Ki67 post ≤ 10%). All other patients (including N0-1 RS12-25 without ET response) received dose-dense chemotherapy (CT) followed by ET in the CT trial. Primary end point of the endocrine trial was noninferiority of 5-year invasive disease-free survival (5y-iDFS) in experimental ( v control) arm; secondary end points included distant DFS, overall survival, and translational research.
Results: Intention-to-treat population comprised 2,290 patients (n = 1,422 experimental v n = 868 control): 26.3% versus 34.6% premenopausal and 27.4% versus 24.0% pN1. One-sided 95% lower confidence limit of the 5y-iDFS difference was -3.3%, establishing prespecified noninferiority ( P = .05). 5y-iDFS was 92.6% (95% CI, 90.8 to 94.0) in experimental versus 93.9% (95% CI, 91.8 to 95.4) in control arm; 5-year distant DFS was 95.6% versus 96.3%, and 5-year overall survival 97.3% versus 98.0%, respectively. Differences were similar in age and nodal subgroups. In N0-1 RS12-25, outcome of ET responders (ET alone) was comparable with that of ET nonresponders (CT) for age > 50 years and superior for age ≤ 50 years. ET response was more likely with aromatase inhibitors (mostly postmenopausal) than with tamoxifen (mostly premenopausal): 78.1% versus 41.1% ( P < .001). ET response was 78.8% in RS0-11, 62.2% in RS12-25, and 32.7% in RS > 25 (n = 4,203, P < .001).
Conclusion: WSG-ADAPT-HR+/HER2- demonstrates that guiding systemic treatment by both RS and ET response is feasible in clinical routine and spares CT in pre- and postmenopausal patients with ≤ 3 involved lymph nodes.
Databáze: MEDLINE
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