neoadjuvant dose-dense for early her2neu positive breast cancer

Conditions: Locally Advanced Breast Cancer

Summary: primary objective: • determination of pathologic complete response (pcr) rates secondary objective: * determination of cardiac toxicity as measured by: composite of lvef, longitudinal strain and troponin. * breast conservation rates * overall survival study design * approximately 34-74 patients with her2 positive, stage ii-regional iv breast cancer will be enrolled. * patients will be stratified by er/pr status. * they will be randomized to ddacthp vs tchp. * initially, 17 patients will be randomly assigned to each treatment arm. * if 3 or fewer patients have a pcr, then that arm will be terminated and no further patients will be entered on that treatment arm. * if 4 or more patients obtain a pcr, 20 additional patients (total of 37 patients) will be randomized to that treatment arm. * if 11 or more patients out of 37 have a pcr, the treatment will be of interest for further study.


Eligibility criteria:
inclusion criteria: the patient must have signed and dated an irb-approved consent form that conforms to federal and institutional guidelines. * female * 18 years or older * ecog performance status of 0 or 1 * eligible tumors must meet one of the following criteria: * operable (t1c, t2-3, n0-1, m0) * locally advanced (t2-3, n2-3, m0 or t4a-c, any n, m0) * inflammatory breast cancer (t4d, any n, m0) * staging evaluation: * history and physical exam, cbc, chemistry profile * ct chest/abdomen/pelvis and a bone scan or pet/ct as needed * diagnosis of invasive adenocarcinoma made by core needle biopsy * breast cancer determined to be: * confirmed her2-positive : (asco cap guidelines, 10/7/2013) * ihc 3+ based on circumferential membrane staining that is complete, intense * ish positive based on: * single probe average her2 copy number ≥ 6 signals/cell * dual probe her2/cep 17 ratio ≥ 2.0 with an average her2 copy number ≥ 4.0 signals/cell * dual probe her2/cep 17 ratio ≥ 2.0, with an average her2 copy number of \< 4.0 signals/cell * dual probe her2/cep 17 ratio \< 2.0 with the average her2 copy number of ≥ 6.0 signals/cell * any er or pr receptor status * lvef assessment by echocardiogram within 30 days of initiation; ef of ≥ 55% considered normal. * normal troponin i level at baseline * blood counts must meet the following criteria: * anc greater than or equal to 1500/mm3 * platelet count greater than or equal to 100,000/mm3 * hemoglobin greater than or equal to 10 g/dl * serum creatinine less than or equal 2.5 mg/100ml * adequate hepatic function by these criteria: total bilirubin must be less than or equal to 1.5 x the uln for the lab unless the patient has a bilirubin elevation great than the uln to 1.5 x uln due to gilbert's disease or similar syndrome involving slow conjugation of bilirubin; and alkaline phosphatase must be less than or equal to 2.5 x uln for the lab; and ast must be less than or equal to 1.5 x uln for the lab. both alkaline phosphatase and ast may not both be greater than the uln. * patients with ast or alkaline phosphatase \> uln are eligible for inclusion in the study if liver imaging (ct, mri, pet-ct or pet scan) performed within 90 days prior to randomization does not demonstrate metastatic disease and the requirements are met as above * patients with alkaline phosphatase that is \> uln but less than or equal to 2.5 x uln or unexplained bone pain are eligible for inclusion in the study if a bone scan, pet-ct scan, or pet scan performed within 90 days prior to randomization does not demonstrate metastatic disease. exclusion criteria: patients with a history of decompensated congestive heart failure or an ef \< 55% will be excluded • cardiac disease that would preclude the use of the drugs included in the above regimens. this includes but is not confined to: * active cardiac disease: * angina pectoris requiring the use of anti-anginal medication; * ventricular arrhythmias except for benign premature ventricular contractions controlled by medication; * conduction abnormality requiring a pacemaker; * supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication; and * clinically significant valvular disease * symptomatic pericarditis * pulmonary hypertension * history of cardiac disease: * myocardial infarction; * congestive heart failure; or * cardiomyopathy

Keywords: neoadjuvant chemotherapy locally advanced breast cancer her2neu