The run-in phase of the prospective WSG-ADAPT HR+/HER2-trial demonstrates the feasibility of a study design combining static and dynamic biomarker assessments for individualized therapy in early breast cancer

Background: Endocrine sensitivity, as determined by response of the proliferation marker Ki-67 to short-term preoperative endocrine therapy (ET), is currently not included in adjuvant treatment decisions in hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)- breast cancer (BC). Methods: The prospective WSG-ADAPT HR+/HER2- trial included patients with N0/N1 early BC who were candidates for adjuvant chemotherapy based on clinical-pathological criteria alone. The trial utilized a genomic assessment [the Recurrence Score (RS)] plus endocrine sensitivity testing to guide treatment. All patients received 3 (+/- 1) weeks of preoperative induction ET. According to protocol, patients with RS 0-11 or RS 12-25 plus endocrine proliferation response (EPR, post-induction Ki-67 <= 10%) were to be spared adjuvant chemotherapy. Results: The ADAPT HR+/HER2- trial run-in phase included 407 patients with baseline RS, of whom 386 (median age: 54 years) had complete data for Ki-67 at both baseline and post-induction. RS distribution: 23.1% RS 0-11, 58.3% RS 12-25, and 18.7% RS 26-100. EPR occurred in 84.3%, 76.0%, and 36.1% of these RS groups, respectively. Differences in EPR proportions (RS 26-100 versus others, RS 0-11 versus others) were significant (both p < 0.001); Ki-67 quotients were higher for RS 26-100 (p = 0.02, Mann-Whitney). In premenopausal women (n = 146, mostly tamoxifen-treated), median quotient of Ki-67 level (post/pre) was significantly higher than in postmenopausal women (n = 222, mostly aromatase-inhibitor treated; 0.67 versus 0.25, p < 0.001). EPR was significantly associated with baseline estrogen-receptor status as determined by immunohistochemistry (p = 0.002) or real-time polymerase chain reaction (p < 0.001). Also, a strong correlation was observed between RS measured pre- and post-ET (R-S = 0.7, n = 181). Conclusions: This phase of the WSG-ADAPT HR+/HER2- trial confirms trial design estimates of RS and EPR. It indicates that the ADAPT concep