HER-2 Positive Breast Cancer

Evaluation of the efficacy of A166 in Patients with HER2-Positive unresectable or metastatic breast cancer previously treated with TOP1 inhibitor Antibody-Drug Conjugates

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.

The usual approach to care for hormone receptor positive, HER2 positive breast cancer is chemotherapy and HER2 targeted therapy followed by endocrine therapy and surgery. The purpose of this Research Study is to see if taking endocrine therapy with the chemotherapy and HER2 directed therapy increases patients response to therapy at the time of surgery

The goal of this observational study is to describe the real-world utilization patterns of a pertuzumab biosimilar and to evaluate its clinical outcomes in patients with breast cancer in both neoadjuvant and metastatic settings. It also aims to assess pathological complete response (pCR), disease-free survival (DFS) in the neoadjuvant cohort, progression-free survival (PFS) in the metastatic cohort, overall survival (OS), treatment response, and safety and tolerability (adverse events according to CTCAE) across both cohorts.

Abemaciclib (Verzenio) is a commonly used treatment for hormone receptor-positive breast cancer, but it can cause gastrointestinal side effects such as diarrhea, which may affect quality of life and treatment tolerance. The gut microbiome, which is the collection of bacteria living in the digestive tract, may play a role in these symptoms. The purpose of this study is to examine how the gut microbiome changes during the early phase of abemaciclib treatment and how these changes relate to gastrointestinal symptoms experienced by patients. Participants will provide stool samples at multiple time points using mailed collection kits and will complete questionnaires about gastrointestinal symptoms while receiving standard-of-care abemaciclib therapy. All study procedures will be conducted remotely. Information gained from this study may help inform future supportive care strategies for breast cancer patients receiving abemaciclib.