Neoadjuvant Ixabepilone/Carboplatin/Trastuzumab in HER2-Positive Locally Advanced Breast Cancer

Inclusion Criteria

• Female and male patients ≥18 years of age.
• Histologically confirmed adenocarcinoma of the breast.
• Primary palpable disease confined to a breast and axilla on physical examination. For patients without clinically suspicious axillary adenopathy, the primary tumor must be larger than 2 cm in diameter (clinical T2-T3, N0-N1, M0). For patients with clinically suspicious axillary adenopathy, the primary breast tumor can be any size (clinical T1-T3, N1-N2, M0). (T1N0M0 lesions are excluded.)
• Patients who have no clearly defined palpable breast mass or axillary lymph nodes but are radiographically measurable are eligible. Accepted procedures for measuring breast disease are mammography, MRI, and breast ultrasound. In these patients, radiographic tumor measurements need to be repeated after 3 cycles and prior to surgery.
• Positive HER2 status (overexpression and/or amplification of HER2 in the primary tumor) as defined by: IHC 3+ or fluorescence in situ hybridization (FISH) positive (ratio >2.2) testing. Documentation of the HER2 results must be available at the time of study enrollment.
• An ECOG (Eastern Cooperative Oncology Group) performance score of ≤2
• Normal bone marrow function as defined by:
• absolute neutrophil count (ANC) >1,500/µL;
• platelets >100,000/µL;
• hemoglobin >10 g/dL.
• Normal hepatic and renal function.
• Left ventricular ejection fraction (LVEF) within the institutional limits of normal, whichever is lower, as measured by multi-gated acquisition (MUGA) scan or echocardiogram (ECHO).
• Life expectancy > 12 weeks.
• Estrogen and progesterone (or estrogen alone) receptor status in the primary tumor known or pending at the time of study enrollment.
• For women of childbearing potential, negative serum pregnancy test within 7 days prior to starting treatment.
• For women of childbearing potential, agreement to use a method of contraception that is acceptable to their physician from time of first signing the informed consent until at least 3 months after the last dose of study drug. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately. Patient agreement to discontinue breast-feeding, if applicable, during study treatment. Men enrolled in the study must also agree to use a method of contraception that is acceptable to their physician during their study participation.
• For patients with previous invasive cancers (including breast cancer) treated with curative intent, completion of chemotherapy or radiation therapy more than 5 years prior to enrollment for this study and no evidence of recurrent disease. Patients may be receiving anti-estrogen hormonal therapy prescribed for previous invasive breast cancer as long as the diagnosis of invasive cancer was made more than 5 years prior to study enrollment. Patients may be using anti-estrogen hormonal therapy at the time of current diagnosis but must discontinue this therapy before beginning study treatment.
• For patients who had, or will have sentinel lymph node and/or axillary dissection prior to initiation of study treatment, completion at least 4 weeks prior to starting study treatment and well-healed wound.
• Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria

• Previous treatment for this breast cancer.
• Evidence of metastatic disease.
• Prior radiation that included ≥30% of major bone marrow-containing areas.
• Women who are pregnant or breastfeeding.
• Neuropathy (motor or sensory) ≥grade 1 at study entry.
• History of significant cardiac disease or cardiac risk factors or the following:
• uncontrolled arrhythmias
• poorly controlled hypertension (e.g., systolic blood pressure [BP]> 150 mmHg or diastolic BP >100 mmHg) in spite of optimal medical management
• angina pectoris requiring antianginal medication or unstable angina within the previous 6 months