Brief Summary This is an open-label, randomized, phase II clinical study designed to evaluate neoadjuvant treatment regimens in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) early breast cancer.
A total of 60 premenopausal, perimenopausal, and postmenopausal patients with HR+/HER2- breast cancer who meet the inclusion criteria will be enrolled. During the study, clinical information will be collected according to standard practice, including demographic data, tumor imaging, and pathological results (e.g., Ki-67). Investigator-assessed outcomes will be used as the final results.
After 14 days of treatment, patients who provide consent will undergo a second biopsy to evaluate the rate of complete cell-cycle arrest. Safety assessments and imaging evaluations will be performed at treatment completion or upon study withdrawal. Informed consent must be obtained at each study center before participation.
Treatment arms:
Arm A (30 patients):
Dalpiciclib 125 mg orally once daily on Days 1-21 of each 28-day cycle (3 weeks on, 1 week off), for 6 cycles Letrozole 2.5 mg orally once daily continuously for 6 cycles Entinostat 3 mg orally once weekly (Days 1-28 of each 28-day cycle), for 6 cycles
Arm B (30 patients):
Dalpiciclib 150 mg orally once daily on Days 1-21 of each 28-day cycle, for 6 cycles Letrozole 2.5 mg orally once daily continuously for 6 cycles Premenopausal and perimenopausal women will also receive ovarian function suppression (OFS), such as with a GnRHa agent.
After signing informed consent, patients will begin neoadjuvant therapy with dalpiciclib plus entinostat and letrozole ± OFS. Ultrasound assessments will be conducted every two treatment cycles and before surgery under the same imaging conditions as baseline. Bone scans will be performed at the end of neoadjuvant treatment. MRI of the breast will be performed at baseline, after two cycles, and before surgery to assess treatment efficacy. Treatment discontinuation will occur if toxicity is intolerable, consent is withdrawn, or the investigator determines it is necessary.
Adjuvant therapy:
After surgery, patients will receive physician's choice of therapy (TPC).
Safety follow-up:
Patients will be followed until they start another anticancer therapy, all adverse events have resolved to Grade 0-1 or baseline level, or death-whichever occurs first.