Optimize Neoadjuvant Therapy in HER2-Positive Early-Stage Breast Cancer

Inclusion criteria

• Tumor size greater than 2cm or lymph node positive by imaging or clinical exam (cT2-T3 N0-2)
• Tumors must be HER2 positive either by IHC (3+) or by IHC 2+ and FISH positive.
• Patient must have known estrogen receptor (ER) and progesterone receptor (PR) status locally determined prior to study entry
• Patient must have adequate tumor for HARPS testing.
• Patients must have ctDNA collection prior to treatment on trial.
• Patient must be able to do breast MRI as determined by the study
• Baseline LVEF \> 50% (Most recent within the last 5 years)
• No prior history of systemic treatment with anthracyclines-based chemotherapy.
• Adequate bone marrow function:
• ANC ≥ 1500/uL
• platelet count ≥ 100,000/uL
• hemoglobin ≥ 9.0 g/dL
• Adequate hepatic function:
• Total bilirubin ≤ 1.5 X ULN
• AST (SGOT) ≤ 5 X ULN
• ALT (SGPT) ≤ 5 X ULN
• Patients with biliary obstruction must have restored biliary flow by placement of an endoscopic common bile duct stent or a percutaneous drainage.
• Adequate renal function, Creatinine \< 1.5x institutional ULN or calculated creatinine clearance ≥ 50 mL/min as estimated using the Cockcroft-Gault formula.
• Ability to understand the nature of this study protocol and give written informed consent.
• Willingness and ability to comply with scheduled visits and treatment plans
• Prior cancers allowed if no evidence of disease in last 5 years. Prior history of ipsilateral invasive breast cancers are not allowed.

Exclusion criteria

• Previous treatment with chemotherapy, anti-HER2 therapy, radiation therapy, or endocrine therapy for invasive breast cancer. Exception: patients can start upto 1 cycle of HP prior to starting treatment on study.
• cT4 and/or cN3 tumors
• Evidence of metastatic disease by routine clinical assessment
• Bilateral breast cancer
• History of other malignancy within the last five years prior to first dose of study drug administration, except for curatively treated basal and squamous cell carcinoma of the skin and/or in situ cervical carcinoma
• Left ventricular ejection fraction (LVEF) below 50% as determined by multiple-gated acquisition (MUGA) scan or echocardiography (ECHO)
• No active liver disease.
• Any condition including the presence of laboratory abnormalities, which, in the opinion of the investigator places the subject at unacceptable risk if he/she were to participate in the study.
• Pre-existing sensory neuropathy \> grade 1.
• Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 6 months.
• Serious non-healing wound, ulcer, or bone fracture
• Patient with uncontrolled and/ or active infection with HIV, Hepatitis B or Hepatitis C.
• Patient who has a history of allergy or hypersensitivity to any of the study drugs.
• Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study