Phase II Study of Ultrasound and ctDNA Guided Neoadjuvant Systemic Therapy for Patients With HER2-positive Early Breast Cancer (UC HER Trial)

Although neoadjuvant dual anti-HER2-targeted therapy, pertuzumab and trastuzumab, combined with taxanes increased the pCR rate for patients with early-stage HER2-positive breast cancer when compared with single blockade combined with chemotherapy, certain patients did not achieve pCR after receiving dual blockade or single blockade targeting HER2 combined with taxanes.

Based on the cardiac safety and promising ORR rate of the regimens consisting of PLD and cyclophosphamide and trastuzumab in treating patients with HER2-positive breast cancer in the neoadjuvant or metastatic setting, the investigators hypothesized that dual blockades targeting HER2, trastuzumab and pertuzumab, combined with PLD and cyclophosphamide, will not only increase the pCR rate but also cause less cardiotoxicity for participants with residual cancer via core biopsy or non-clinical CR after receiving taxanes plus trastuzumab and pertuzumab or taxanes plus trastuzumab. The investigators also showed that ctDNA served as the surrogate prognostic marker for participants with HER2-positive EBC who received neoadjuvant trastuzumab-based regimens.

In this study, the investigators will explore whether the combination of PLD (Lipo-Dox®, Liposomal Doxorubicin Injection), cyclophosphamide, trastuzumab, and pertuzumab can increase the pCR rate of participants with HER2-positive EBC if they have residual cancers (core biopsy, non-clinical CR, or positive ctDNA) after receiving a trastuzumab and taxanes-based NAT regimen. In addition, the cardiac safety, adverse effects, and clearance of ctDNA will be explored for these patients. The investigators further assess the feasibility of VAB (before operation) in these participants who achieved negative ctDNA after receiving Lipo-Dox® plus cyclophosphamide, trastuzumab, and pertuzumab.