Annals of oncology : official journal of the European Society for Medical Oncology · 2026
Clinical and molecular biomarkers for prediction of endocrine response after short preoperative endocrine therapy in the WSG ADAPT-HR+/HER2- and ADAPTcycle trials (N = 7914).
СтатьяРандомизированное исследованиеНазвание и аннотация: Перевод в очереди
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Gluz O, Nitz U, Christgen M, Kuemmel S, Braun M, Thill M, Wuerstlein R, Link T, Aktas B, Lüdtke-Heckenkamp K, Zaiss M, Bjelic-Radisic V, Just M, Veselinovic K, Vincent M, Baehner R, Wujak L, Warm M, Schumacher C, Schem C, Forstbauer H, Krauss K, Hoffmann O, Graeser M, Hartkopf A, Kates R, Zu Eulenburg C, Jóźwiak K, Burmeister S, Schmid P, Kreipe H H, Harbeck N, WSG ADAPT investigators
Аннотация
BACKGROUND: Low Ki67 after short preoperative endocrine therapy (ET) indicates a favorable prognosis in hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative early breast cancer (eBC). We investigated predictors of ET response in the West German Study Group (WSG) ADAPT-HR+/HER2- and ADAPTcycle trials.
PATIENTS AND METHODS: ET response (Ki67 ≤10%) after 2- to 4-week standard ET, recurrence score (RS), and nodal status were used for treatment allocation. In ADAPT-HR+/HER2-, patients at high clinical risk received ET alone if N0-1 and RS 0-11 or RS 12-25 and ET response. In ADAPTcycle, N0-1 patients with RS > 25 and ET response and those with RS < 25 and e.g. ET nonresponse, N2-3 patients with RS ≤ 25 and ET response, were randomly assigned to receive (neo)adjuvant chemotherapy or aromatase inhibitor (AI)+ribociclib. Predictors of ET response were identified through multivariable logistic regression models.
RESULTS: Three thousand six hundred seventy-five patients from the ADAPT-HR+/HER2- cohort (≤50 years and premenopausal, ≤50 years: N = 1250; >50 years or postmenopausal, >50 years: N = 2425) and 4239 from the ADAPTcycle screening cohort (≤50 years: N = 1336; >50 years: N = 2903) were analyzed. ET response rates were higher after AI (ADAPT-HR+/HER2-/ADAPTcycle: 81.4%/76.7%) versus tamoxifen (ADAPT-HR+/HER2-/ADAPTcycle: 40.1%/34.7%) in both age groups, with further improvement by ovarian function suppression (OFS) in premenopausal patients. Premenopausal patients with GnRH plus AI had similar ET response rates as postmenopausal patients. ET response predictors included AI use (plus OFS in premenopausal), age >50 years, lower RS and baseline Ki67 levels, and higher expression of estrogen receptor (by immunohistochemistry) and HER2 (by Oncotype DX™). In ADAPT-HR+/HER2-, 5-year distant disease-free survival in ET responders was markedly higher than in nonresponders and also in chemotherapy-treated N0-1 patients with RS > 25 (87.0 versus 80.7%), and it was only slightly lower than that in the RS 12-25 group.
CONCLUSIONS: We observed similar ET response rates in two large phase III trials. Postmenopausal patients (mostly receiving AI) had higher ET response rates than younger patients. However, young patients with GnRH+AI had ET response rates comparable with those of postmenopausal patients, suggesting that therapy rather than biology accounts for the difference. Combining ET response and gene expression assessment could help more patients with luminal eBC avoid chemotherapy.
PATIENTS AND METHODS: ET response (Ki67 ≤10%) after 2- to 4-week standard ET, recurrence score (RS), and nodal status were used for treatment allocation. In ADAPT-HR+/HER2-, patients at high clinical risk received ET alone if N0-1 and RS 0-11 or RS 12-25 and ET response. In ADAPTcycle, N0-1 patients with RS > 25 and ET response and those with RS < 25 and e.g. ET nonresponse, N2-3 patients with RS ≤ 25 and ET response, were randomly assigned to receive (neo)adjuvant chemotherapy or aromatase inhibitor (AI)+ribociclib. Predictors of ET response were identified through multivariable logistic regression models.
RESULTS: Three thousand six hundred seventy-five patients from the ADAPT-HR+/HER2- cohort (≤50 years and premenopausal, ≤50 years: N = 1250; >50 years or postmenopausal, >50 years: N = 2425) and 4239 from the ADAPTcycle screening cohort (≤50 years: N = 1336; >50 years: N = 2903) were analyzed. ET response rates were higher after AI (ADAPT-HR+/HER2-/ADAPTcycle: 81.4%/76.7%) versus tamoxifen (ADAPT-HR+/HER2-/ADAPTcycle: 40.1%/34.7%) in both age groups, with further improvement by ovarian function suppression (OFS) in premenopausal patients. Premenopausal patients with GnRH plus AI had similar ET response rates as postmenopausal patients. ET response predictors included AI use (plus OFS in premenopausal), age >50 years, lower RS and baseline Ki67 levels, and higher expression of estrogen receptor (by immunohistochemistry) and HER2 (by Oncotype DX™). In ADAPT-HR+/HER2-, 5-year distant disease-free survival in ET responders was markedly higher than in nonresponders and also in chemotherapy-treated N0-1 patients with RS > 25 (87.0 versus 80.7%), and it was only slightly lower than that in the RS 12-25 group.
CONCLUSIONS: We observed similar ET response rates in two large phase III trials. Postmenopausal patients (mostly receiving AI) had higher ET response rates than younger patients. However, young patients with GnRH+AI had ET response rates comparable with those of postmenopausal patients, suggesting that therapy rather than biology accounts for the difference. Combining ET response and gene expression assessment could help more patients with luminal eBC avoid chemotherapy.
Предметные рубрики MeSH
HumansFemaleBreast NeoplasmsErb-b2 Receptor Tyrosine KinasesBiomarkers, TumorMiddle AgedReceptors, EstrogenKi-67 AntigenAdultPrognosisAromatase InhibitorsAntineoplastic Agents, HormonalAntineoplastic Combined Chemotherapy ProtocolsAgedTamoxifenNeoadjuvant TherapyChemotherapy, AdjuvantNeoplasm Recurrence, LocalReceptors, Progesterone